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Sample records for antifungals myclobutanil propiconazole

  1. Toxicity profiles in rats treated with tumorigenic and nontumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.

    PubMed

    Wolf, Douglas C; Allen, James W; George, Michael H; Hester, Susan D; Sun, Guobin; Moore, Tanya; Thai, Sheau-Fung; Delker, Don; Winkfield, Ernest; Leavitt, Sharon; Nelson, Gail; Roop, Barbara C; Jones, Carlton; Thibodeaux, Julie; Nesnow, Stephen

    2006-01-01

    Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have a common mode of antifungal action through inhibition of ergosterol biosynthesis. Some members of this class have been shown to be hepatotoxic and will induce mouse hepatocellular tumors and/or rat thyroid follicular cell tumors. The particular mode of toxic and tumorigenic action for these compounds is not known, however it has been proposed that triadimefon-induced rat thyroid tumors arise through the specific mechanism of increased TSH. The present study was designed to identify commonalities of effects across the different conazoles and to determine unique features of the tissue responses that suggest a toxicity pathway and a mode of action for the observed thyroid response for triadimefon. Male Wistar/Han rats were treated with triadimefon (100, 500, 1800 ppm), propiconazole (100, 500, 2500 ppm), or myclobutanil (100, 500, 2000 ppm) in feed for 4, 30, or 90 days. The rats were evaluated for clinical signs, body and liver weight, histopathology of thyroid and liver, hepatic metabolizing enzyme activity, and serum T3, T4, TSH, and cholesterol levels. There was a dose-dependent increase in liver weight but not body weight for all treatments. The indication of cytochrome induction, pentoxyresorufin O-dealkylation (PROD) activity, had a dose-related increase at all time points for all conazoles. Uridine diphopho-glucuronosyl transferase (UDPGT), the T4 metabolizing enzyme measured as glucuronidation of 1-naphthol, was induced to the same extent after 30 and 90 days for all three conazoles. Livers from all high dose treated rats had centrilobular hepatocyte hypertrophy after 4 days, while only triadimefon and propiconazole treated rats had hepatocyte hypertrophy after 30 days, and only triadimefon treated rats had hepatocyte hypertrophy after 90 days. Thyroid follicular cell hypertrophy, increased follicular cell proliferation, and colloid depletion were

  2. Toxicity profiles in mice treated with hepatotumorigenic and non-hepatotumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.

    PubMed

    Allen, James W; Wolf, Douglas C; George, Michael H; Hester, Susan D; Sun, Guobin; Thai, Sheau-Fung; Delker, Don A; Moore, Tanya; Jones, Carlton; Nelson, Gail; Roop, Barbara C; Leavitt, Sharon; Winkfield, Ernest; Ward, William O; Nesnow, Stephen

    2006-01-01

    Conazoles comprise a class of fungicides used in agriculture and as pharmaceutical products. The fungicidal properties of conazoles are due to their inhibition of ergosterol biosynthesis. Certain conazoles are tumorigenic in rodents; both propiconazole and triadimefon are hepatotoxic and hepatotumorigenic in mice, while myclobutanil is not a mouse liver tumorigen. As a component of a large-scale study aimed at determining the mode(s) of action for tumorigenic conazoles, we report the results from comparative evaluations of liver and body weights, liver histopathology, cell proliferation, cytochrome P450 (CYP) activity, and serum cholesterol, high-density lipoprotein and triglyceride levels after exposure to propiconazole, triadimefon, and myclobutanil. Male CD-1 mice were treated in the feed for 4, 30, or 90 days with triadimefon (0, 100, 500, or 1800 ppm), propiconazole (0, 100, 500, or 2500 ppm) or myclobutanil (0, 100, 500, or 2000 ppm). Alkoxyresorufin O-dealkylation (AROD) assays indicated that all 3 chemicals induced similar patterns of dose-related increases in metabolizing enzyme activity. PROD activities exceeded those of MROD, and EROD with propiconazole inducing the highest activities of PROD. Mice had similar patterns of dose-dependent increases in hepatocyte hypertrophy after exposure to the 3 conazoles. High-dose exposures to propiconazole and myclobutanil, but not triadimefon, were associated with early (4 days) increases in cell proliferation. All the chemicals at high doses reduced serum cholesterol and high-density lipoprotein (HDL) levels at 30 days of treatment, while only triadimefon had this effect at 4 days of treatment and only myclobutanil and propiconazole at 90 days of treatment. Overall, the tumorigenic and nontumorigenic conazoles induced similar effects on mouse liver CYP enzyme activities and pathology. There was no specific pattern of tissue responses that could consistently be used to differentiate the tumorigenic conazoles

  3. Behavior of myclobutanil, propiconazole, and nuarimol residues during lager beer brewing.

    PubMed

    Navarro, Simón; Pérez, Gabriel; Vela, Nuria; Mena, Luis; Navarro, Ginés

    2005-11-01

    Over a 4 month brewing process, the fate of three fungicides, myclobutanil, propiconazole, and nuarimol, was studied in the spent grain, brewer wort, and final beer product. Only the residual level of myclobutanil after the mashing step was higher than its maximum residue limit (MRL) on barley. A substantial fraction was removed with the spent grain in all cases (26-42%). The half-life times obtained for the fungicides during storage of the spent grains ranged from 82 to 187 days. No significant influence of the boiling stage on the decrease of the fungicide residues was demonstrated. During fermentation, the content reduction varied from 20 to 47%. After the lagering and filtration steps, no significant decrease (<10%) was observed in any of the residues. Finally, during storage of the beer (3 months), the amounts of fungicides fell by 25-50% of their respective concentrations in the finished beer.

  4. TRANSCRIPTIONAL PROFILES IN LIVER FROM RATS TREATED WITH TUMORIGENIC AND NON-TUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDES: PROPICONAZOLE, TRIADIMEFON, AND MYCLOBUTANIL

    EPA Science Inventory

    Conazoles are a class of fungicides used as pharmaceutical and agricultural agents. In chronic bioassays in rats, triadimefon was hepatotoxic and induced follicular cell adenomas in the thyroid gland, whereas, propiconazole and myclobutanil were hepatotoxic but had no effect on t...

  5. Transcriptional profiles in liver from rats treated with tumorigenic and non-tumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.

    PubMed

    Hester, Susan D; Wolf, Douglas C; Nesnow, Stephen; Thai, Sheau-Fung

    2006-01-01

    Conazoles are a class of fungicides used as pharmaceutical and agricultural agents. In chronic bioassays in rats, triadimefon was hepatotoxic and induced follicular cell adenomas in the thyroid gland, whereas, propiconazole and myclobutanil were hepatotoxic but had no effect on the thyroid gland. These conazoles administered in the feed to male Wistar/Han rats were found to induce hepatomegaly, induce high levels of pentoxyresorufin-O-dealkylase, increase cell proliferation in the liver, increase serum cholesterol, decrease serum T3 and T4, and increase hepatic uridine diphosphoglucuronosyl transferase activity. The goal of the present study was to define pathways that explain the biologic outcomes. Male Wistar/Han rats (3 per group), were exposed to the 3 conazoles in the feed for 4, 30, or 90 days of treatment at tumorigenic and nontumorigenic doses. Hepatic gene expression was determined using high-density Affymetrix GeneChips (Rat 230_2). Differential gene expression was assessed at the probe level using Robust Multichip Average analysis. Principal component analysis by treatment and time showed within group sample similarity and that the treatment groups were distinct from each other. The number of altered genes varied by treatment, dose, and time. The greatest number of altered genes was induced by triadimefon and propiconazole after 90 days of treatment, while myclobutanil had minimal effects at that time point. Pathway level analyses revealed that after 90 days of treatment the most significant numbers of altered pathways were related to cell signaling, growth, and metabolism. Pathway level analysis for triadimefon and propiconazole resulted in 71 altered pathways common to both chemicals. These pathways controlled cholesterol metabolism, activation of nuclear receptors, and N-ras and K-ras signaling. There were 37 pathways uniquely changed by propiconazole, and triadimefon uniquely altered 34 pathways. Pathway level analysis of altered gene expression

  6. Transcriptional profiles in liver from mice treated with hepatotumorigenic and nonhepatotumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.

    PubMed

    Ward, William O; Delker, Don A; Hester, Susan D; Thai, Sheau-Fung; Wolf, Douglas C; Allen, James W; Nesnow, Stephen

    2006-01-01

    Conazoles are environmental and pharmaceutical fungicides. The present study relates the toxicological effects of conazoles to alterations of gene and pathway transcription and identifies potential modes of tumorigenic action. In a companion study employing conventional toxicological bioassays (Allen et al., 2006), male CD-1 mice were fed triadimefon, propiconazole, or myclobutanil in a continuous oral-dose regimen for 4, 30, or 90 days. These conazoles were found to induce hepatomegaly, to induce high levels of hepatic pentoxyresorufin-O-dealkylase activity, to increase hepatic cell proliferation, to decrease serum cholesterol, and to increase serum triglycerides. Differentially expressed genes and pathways were identified using Affymetrix GeneChips. Gene-pathway associations were obtained from the Kyoto Encyclopedia of Genes and Genomes, Biocarta, and MetaCore compendia. The pathway profiles of each conazole were different at each time point. In general, the number of altered metabolism, signaling, and growth pathways increased with time and dose and were greatest with propiconazole. All conazoles had effects on nuclear receptors as evidenced by increased expression and enzymatic activities of a series of related cytochrome P450s (CYP). A subset of altered genes and pathways distinguished the three conazoles from each other. Triadimefon and propiconazole both altered apoptosis, cell cycle, adherens junction, calcium signaling, and EGFR signaling pathways. Triadimefon produced greater changes in cholesterol biosynthesis and retinoic acid metabolism genes and in selected signaling pathways. Propiconazole had greater effects on genes responding to oxidative stress and on the IGF/P13K/AKt/PTEN/mTor and Wnt-beta-catenin pathways. In conclusion, while triadimefon, propiconazole, and myclobutanil had similar effects in mouse liver on hepatomegaly, histology, CYP activities, cell proliferation, and serum cholesterol, genomic analyses revealed major differences in their

  7. Inhibition of Rat and Human Steroidogenesis by Triazole Antifungals

    EPA Science Inventory

    Environmental chemicals that alter steroid production could interfere with male reproductive development and function. Three agricultural antifungal triazoles (myclobutanil, propiconazole and triadimefon) that are known to modulate expression of cytochrome P450 (CYP) genes and e...

  8. Toxicogenomic Effects Common to Triazole Antifungals and Conserved Between Rats and Humans

    EPA Science Inventory

    The triazole antifungals myclobutanil, propiconazole and triadimefon cause varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in rodent in vivo models. To identify biological pathways consistently modulated across multiple time-points and various study d...

  9. TOXICITY PROFILES IN RATS TREATED WITH TUMORIGENIC AND NONTUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDES: PROPICONAZOLE, TRIADIMEFON, AND MYCLOBUTANIL

    EPA Science Inventory

    Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have a common mode of antifungal action through inhibition of ergosterol biosynthesis. Some members of this class have been shown to be hepatotoxic and will induce mouse hepa...

  10. TOXICITY PROFILES IN MICE TREATED WITH HEPATOTUMORIGENIC AND NON-HEPATOTUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDES: PROPICONAZOLE, TRIADIMEFON, AND MYCLOBUTANIL

    EPA Science Inventory

    Conazoles comprise a class of fungicides used in agriculture and as pharmaceutical products. The fungicidal properties of conazoles are due to their inhibition of ergosterol biosynthesis. Certain conazoles are tumorigenic in rodents; both propiconazole and triadimefon are hepatot...

  11. Propiconazole

    Integrated Risk Information System (IRIS)

    Propiconazole ; CASRN 60207 - 90 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  12. Inhibition of rat and human steroidogenesis by triazole antifungals.

    PubMed

    Goetz, Amber K; Rockett, John C; Ren, Hongzu; Thillainadarajah, Inthirany; Dix, David J

    2009-12-01

    Environmental chemicals that alter steroid production could interfere with male reproductive development and function. Three agricultural antifungal triazoles that are known to modulate expression of cytochrome P450 (CYP) genes and enzymatic activities were tested for effects on steroidogenesis using rat in vivo (triadimefon), rat in vitro (myclobutanil and triadimefon), and human in vitro (myclobutanil, propiconazole, and triadimefon) model systems. Hormone production was measured in testis organ cultures from untreated adult and neonatal rats, following in vitro exposure to 1, 10, or 100 muM of myclobutanil or triadimefon. Myclobutanil and triadimefon reduced media levels of testosterone by 40-68% in the adult and neonatal testis culture, and altered steroid production in a manner that indicated CYP17-hydroxylase/17,20 lyase (CYP17A1) inhibition at the highest concentration tested. Rat to human comparison was explored using the H295R (human adrenal adenocarcinoma) cell line. Following 48 h exposure to myclobutanil, propiconazole, or triadimefon at 1, 3, 10, 30, or 100 muM, there was an overall decrease in estradiol, progesterone, and testosterone by all three triazoles. These data indicate that myclobutanil, propiconazole, and triadimefon are weak inhibitors of testosterone production in vitro. However, in vivo exposure of rats to triazoles resulted in increased serum and intra-testicular testosterone levels. This discordance could be due to higher concentrations of triazoles tested in vitro, and differences within an in vitro model system lacking hepatic metabolism and neuroendocrine control.

  13. Development of a difenoconazole/propiconazole microemulsion and its antifungal activities against Rhizoctonia solani AG1-IA.

    PubMed

    Leng, Pengfei; Zhang, Zhiming; Li, Qian; Zhang, Yunsong; Zhao, Maojun; Pan, Guangtang

    2012-06-01

    According to its physical and chemical properties, the composition of difenoconazole/propiconazole microemulsion was as follows: xylene as solvent, emulsifier HSH as surfactant and methanol as cosurfactant. The optimal formulation of difenoconazole/propiconazole microemulsion was oil/SAA/water = 1/2/5 (w/w), in which the SAA consisted of emulsifier HSH and methanol with ratio of 3/2 (w/w). The cloud point of difenoconazole/propiconazole microemulsion was 70 degrees C and its effective ingredient content was 2.5% measured by High Performance Liquid Chromatography (HPLC). Its heat storage stability was studied according to the standards. The decomposition rates of the difenoconazole/propiconazole microemulsion were merely 2.45%, 2.63% respectively and met the Food and Agriculture Organization (FAO) standards of pesticide microemulsion. Investigated by Transmission Electron Microscopy (TEM) the particle size of difenoconazole/propiconazole microemulsion was 90-140 nm and its antifungal activities against Rhizoctonia solani AG1-IA were tested and compared with that of Meiyu. We found that the inhibition rates in the difenoconazole/propiconazole microemulsion treatment group were significantly higher than that of the emulsion group with the same content of effective ingredients and the study also revealed that its inhibiting ability on the formation and germination of sclerotia was significant.

  14. [Evaluation of the antifungal effect of a new propiconazole derivative against 64 yeast strains isolated from vaginal mycosis].

    PubMed

    Mareş, M; Stefanache, Alina; Popovici, Iuliana; Valica, V; Buiuc, D

    2007-01-01

    Worldwide, vaginal candidosis represents a significant health problem in women of childbearing age. The aim of this paper is to evaluate under in vitro conditions resembling the vaginal microenvironment, the antifungal activity of a new propiconazole derivative against 64 strains of yeast species isolated from vulvovaginitis. The tests exhibited low MICs for all strains and this finding may be useful in using of this new azole compound for treatment of mycotic vaginitis.

  15. Synthesis, controlled release properties, and increased antifungal activities of novel cis- and trans-racemate complexes of propiconazole.

    PubMed

    Chen, Xi; Yang, Chunlong

    2009-03-25

    Twenty novel metal complexes M(1)(cis-L)(2)Y(2), M(1)(trans-L)(2)Y(2,) M(2)(cis-L)(4)Y(2), and M(2)(trans-L)(4)Y(2) (M(1) = Zn(II), Co(II), Cu(II); M(2) = Mn(II), Ni(II); Y = OAc, Cl, ClO(4), and NO(3)) were synthesized by reacting bivalent transitional metal salt MY(2).nH(2)O (n = 0-6) with ligands cis-racemate of propiconazole (cis-L) and trans-racemate of propiconazole (trans-L), respectively. All of these synthesized complexes were identified by atomic absorption spectrometry, elemental analysis, and IR and UV spectra. The cumulative release studies of some selected complexes in static water were performed; all determined complexes were found to exhibit attractive controlled release properties, yet the ligand release rates of cis-L complexes were slower than those of trans-L complexes. Meanwhile, it was found that the release rate of ligand cis-L from representative complex Zn(cis-L)(2)Cl(2) was affected obviously by different conditions, such as temperature, pH, and PVA film coating. The antifungal activities of the ligands and their complexes against five selected plant pathogenic fungi were evaluated; the results demonstrated that the toxicity of cis-L was 3.39-5.95 times greater than that of trans-L, and all of the synthesized complexes showed superior activities of 1.19-6.36 times to those of their ligands, especially Zn complexes having toxicities 2.62-6.36 times greater than those of their ligands. Moreover, the cis-L complexes had more sensitive activities than their relevant trans-L complexes; for example, Zn(cis-L)(2)Cl(2) appeared to be 5.00-8.67 times stronger than Zn(trans-L)(2)Cl(2) complex. In addition, the mechanism of increased antifungal activities of the title complexes in comparison with their ligands was discussed preliminarily.

  16. METABOLISM OF MYCLOBUTANIL AND TRIADIMEFON BY HUMAN AND RAT CYTOCHROME P450 ENZYMES AND LIVER MICROSOMES.

    EPA Science Inventory

    Metabolism of two triazole-containing antifungal azoles was studied using expressed human and rat cytochrome P450s (CYP) and liver microsomes. Substrate depletion methods were used due to the complex array of metabolites produced from myclobutanil and triadimefon. Myclobutanil wa...

  17. CAR and PXR-dependent transcriptional changes in the mouse liver after exposure to propiconazole

    EPA Science Inventory

    Exposure to the conazoles propiconazole and triadimefon but not myclobutanilled to tumors in mice after 2 years. Transcript profiling studies in the livers ofwild-type mice after short-term exposure to the conazoles revealed signatures indicating the involvement ofthe nuclear rec...

  18. INDUCTION OF CYTOCHROME P450 ISOFORMS IN RAT LIVER BY TWO CONAZOLES, TRIADIMEFON AND MYCLOBUTANIL

    EPA Science Inventory

    1. This study was undertaken to examine the inductive effects of two triazole antifungal agents, myclobutanil and triadimefon on the expression of hepatic cytochrome P450 (CYP) genes and on the activities of CYP enzymes in male Sprague-Dawley rats. Rats were dosed by gavage for 1...

  19. Integration of toxicological approaches with "omic" and related technologies to elucidate mechanisms of carcinogenic action: propiconazole, an example.

    PubMed

    Nesnow, Stephen

    2013-06-28

    The field of mechanistic chemical carcinogenesis has evolved with the advent and advances in genomic, proteomic and metabolomic technologies. These advances allow mechanistic events along the process of exposure to frank tumors to be studied in great detail. Herein is reviewed an example of this approach using, propiconazole, a triazole-containing antifungal agent that is a mouse hepatocarcinogen. This review will highlight those toxicological, genomic, proteomic and metabolomic findings in mice that were used to describe a set of linked events that lead to propiconazole-induced hepatocarcinogenesis. Independent experimental proof of many of these events is presented that solidified this proposed mechanism of carcinogenic action for propiconazole.

  20. TOXICOGENOMIC STUDY OF TRIAZOLE FUNGICIDES AND PERFLUOROALKYL ACIDS

    EPA Science Inventory

    Toxicogenomic analysis of five environmental contaminants was performed to investigate the ability of genomics to categorize chemicals and elucidate mechanisms of toxicity. Three triazole antifungals (myclobutanil, propiconazole and triadimefon) and two perfluorinated compounds (...

  1. TOXICOGENOMIC STUDY OF TRIAZOLE FUNGICIDES AND PERFLUOROALKYL ACIDS IN RAT LIVERS ACCURATELY CATEGORIZES CHEMICALS AND IDENTIFIES MECHANISMS OF TOXICITY

    EPA Science Inventory

    Toxicogenomic analysis of five environmental chemicals was performed to investigate the ability of genomics to predict toxicity, categorize chemicals, and elucidate mechanisms of toxicity. Three triazole antifungals (myclobutanil, propiconazole, and triadimefon) and two perfluori...

  2. Propiconazole induces alterations in the hepatic metabolome of mice: relevance to propiconazole-induced hepatocarcinogenesis

    EPA Science Inventory

    Propiconazole is a mouse hepatotumorigenic fungicide and has been the subject of recent investigations into its carcinogenic mechanism of action. The goals of this study were: 1. To identify metabolomic changes induced in the liver by increasing doses of propiconazole in mice; 2...

  3. Propiconazole induces alterations in the hepatic metabolome of mice: relevance to propiconazole-induced hepatocarcinogenesis

    EPA Science Inventory

    Propiconazole is a mouse hepatotumorigenic fungicide and has been the subject of recent mechanistic investigations on its carcinogenic mechanism of action. The goals of this study were: 1. To identify metabolomic changes induced in the liver by increasing doses of propiconazole i...

  4. Toxicogenomic effects common to triazole antifungals and conserved between rats and humans

    SciTech Connect

    Goetz, Amber K.; Dix, David J.

    2009-07-01

    The triazole antifungals myclobutanil, propiconazole and triadimefon cause varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in rodent in vivo models. To identify biological pathways consistently modulated across multiple timepoints and various study designs, gene expression profiling was conducted on rat livers from three separate studies with triazole treatment groups ranging from 6 h after a single oral gavage exposure, to prenatal to adult exposures via feed. To explore conservation of responses across species, gene expression from the rat liver studies were compared to in vitro data from rat and human primary hepatocytes exposed to the triazoles. Toxicogenomic data on triazoles from 33 different treatment groups and 135 samples (microarrays) identified thousands of probe sets and dozens of pathways differentially expressed across time, dose, and species - many of these were common to all three triazoles, or conserved between rodents and humans. Common and conserved pathways included androgen and estrogen metabolism, xenobiotic metabolism signaling through CAR and PXR, and CYP mediated metabolism. Differentially expressed genes included the Phase I xenobiotic, fatty acid, sterol and steroid metabolism genes Cyp2b2 and CYP2B6, Cyp3a1 and CYP3A4, and Cyp4a22 and CYP4A11; Phase II conjugation enzyme genes Ugt1a1 and UGT1A1; and Phase III ABC transporter genes Abcb1 and ABCB1. Gene expression changes caused by all three triazoles in liver and hepatocytes were concentrated in biological pathways regulating lipid, sterol and steroid homeostasis, identifying a potential common mode of action conserved between rodents and humans. Modulation of hepatic sterol and steroid metabolism is a plausible mode of action for changes in serum testosterone and adverse reproductive outcomes observed in rat studies, and may be relevant to human risk assessment.

  5. Theoretical study on β-cyclodextrin inclusion complexes with propiconazole and protonated propiconazole.

    PubMed

    Fifere, Adrian; Marangoci, Narcisa; Maier, Stelian; Coroaba, Adina; Maftei, Dan; Pinteala, Mariana

    2012-01-01

    The synthesis of the β-cyclodextrin/propiconazole nitrate inclusion complex and the advantages of the encapsulation of this drug were recently reported, but the experimental data only partially revealed the structure of the supramolecular complex due to the limitations in understanding the intermolecular association mechanism. The present work describes the equilibrium molecular geometries of β-cyclodextrin/propiconazole and β-cyclodextrin/protonated propiconazole, established by the AM1 and PM3 semi-empirical methods. The affinity between different parts of the guest molecule and the cyclodextrin cavity was studied considering that propiconazole possesses three residues able to be included into the host cavity through primary or secondary hydroxyl rims. The results have revealed that the most stable complex is formed when the azole residue of the propiconazole enters the cavity of the cyclodextrin through the narrow hydroxyl's rim.

  6. Bioavailability of butachlor and myclobutanil residues in soil to earthworms.

    PubMed

    Yu, Y L; Wu, X M; Li, S N; Fang, H; Tan, Y J; Yu, J Q

    2005-05-01

    To establish chemical extraction procedures for predicting bioavailability of butachlor and myclobutanil in soil, several solvent systems, including methanol, methanol-water (9:1), methanol-water (1:1), acetone-water (5:3), petroleum ether and water, were assessed for their feasibility in determining extractability of the target compounds from soil samples. Experimental data showed that the extractability of butachlor and myclobutanil by the solvents was well linearly correlated with their bioavailability to Eisenia foetida and Allolobophora caliginosa, indicating that these extraction procedures may be efficient for predicting bioavailability of the two pesticides. The concentrations of the pesticides accumulated in E. foetida and A. caliginosa varied with species, suggesting that the availability of the soil-sequestered pesticide is a species-dependent process.

  7. Instability of Propiconazole Resistance and Fitness in Monilinia fructicola.

    PubMed

    Cox, K D; Bryson, P K; Schnabel, G

    2007-04-01

    ABSTRACT The fitness and the dynamics of demethylation inhibitor fungicide (DMI) sensitivity in isolates of Monilinia fructicola sensitive (no growth at 0.3 mg/liter propiconazole) and resistant (>/=50% relative growth at 0.3 mg/liter propiconazole) to propiconazole were investigated. Overall, there was no considerable compromise in the fitness of resistant isolates compared to sensitive isolates of M. fructicola at the time of collection. Resistant and sensitive isolates differed in their sensitivity to propiconazole (P < 0.001) and incubation period (P = 0.044), but not in latent period, growth rate, spore production, and spore germination frequency (P > 0.05). Consecutive transferring on potato dextrose agar had an impact on conidia production, conidial germination, and growth rate (P < 0.0001). Consecutive transferring also had an impact on propiconazole sensitivity in resistant isolates. In the resistant isolates, sensitivity to propiconazole increased (R(2) = 0.960, P = 0.0034) within the first eight transfers. Similarly, sensitivity to propiconazole increased by 273% over the course of 34 months in cold storage in propiconazole-resistant isolates. Our results show that propiconazole resistance is unstable in vitro and that standard subculturing and cold storage procedures impact propiconazole sensitivity of resistant isolates. The instability of propiconazole resistance in M. fructicola may have important implications for disease management in that a reversion to propiconazole sensitivity could potentially occur in the absence of DMI fungicide pressure in the field.

  8. Phototransformation of propiconazole in aqueous media.

    PubMed

    Vialaton, D; Pilichowski, J F; Baglio, D; Paya-Perez, A; Larsen, B; Richard, C

    2001-11-01

    The photolysis of propiconazole in pure water, in water containing humic substances, and in natural water was investigated. The reaction rates were determined, and the main photoproducts were identified with the help of HPLC-mass spectrometry and by NMR. The quantum yield for direct photolysis was 0.11 +/- 0.01 at the maximum of absorption (269 nm). Photocyclization after HCl elimination and photohydrolysis of the cyclized intermediate were the main reaction pathways at 254 nm. By contrast, oxidation prevailed over dechlorination in simulated or natural solar light. Humic substances (10 mg x L(-)(1)) and naturally occurring chromophores contained in natural water enhanced the rate of propiconazole photodegradation in solar light. Half-life in June in Clermont-Ferrand (latitude 46 degrees N) was found to be 85 +/- 10 h in pure water and 60 +/- 10 h in natural water; showing that photodegradation of propiconazole in natural waters involves both direct photolysis and photoinduced reactions.

  9. TRANSCRIPTIONAL PROFILES IN LIVER FROM MICE TREATED WITH HEPATOTUMORIGENIC AND NON-HEPATOTUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDES: PROPICONAZOLE, TRIADIMEFON, AND MYCLOBUTANIL

    EPA Science Inventory

    Conazoles are environmental and pharmaceutical fungicides. The present study relates the toxicological effects of conazoles to alterations of gene and pathway transcription and identifies potential modes of tumorigenic action. In a companion study (Allen et al. 2006) under...

  10. Enantioselectivity in tebuconazole and myclobutanil non-target toxicity and degradation in soils.

    PubMed

    Li, Yuanbo; Dong, Fengshou; Liu, Xingang; Xu, Jun; Han, Yongtao; Zheng, Yongquan

    2015-03-01

    Tebuconazole and myclobutanil are two widely used triazole fungicides, both comprising two enantiomers with different fungicidal activity. However, their non-target toxicity and environmental behavior with respect to enantioselectivity have received limited attention. In the present study, tebuconazole and myclobutanil enantiomers were isolated and used to evaluate the occurrence of enantioselectivity in their acute toxicity to three non-target organisms (Scenedesmus obliquus, Daphnia magna, and Danio rerio). Significant differences were found: R-(-)-tebuconazole was about 1.4-5.9 times more toxic than S-(+)-tebuconazole; rac-myclobutanil was about 1.3-6.1 and 1.4-7.3 more toxic than (-)-myclobutanil and (+)-myclobutanil, respectively. Enantioselectivity was further investigated in terms of fungicide degradation in seven soil samples, which were selected to cover a broad range of soil properties. In aerobic or anaerobic soils, the S-(+)-tebuconazole degraded faster than R-(-)-tebuconazole, and the enantioselectivity showed a correlation with soil organic carbon content. (+)-Myclobutanil was preferentially degraded than (-)-myclobutanil in aerobic soils, whereas both enantiomers degraded at similar rates in anaerobic soils. Apparent correlations of enantioselectivity with soil pH and soil texture were observed for myclobutanil under aerobic conditions. In addition, both fungicides were configurationally stable in soils, i.e., no enantiomerization was found. Enantioselectivity may be a common phenomenon in both aquatic toxicity and biodegradation of chiral triazole fungicides, and this should be considered when assessing ecotoxicological risks of these compounds in the environment. PMID:25475972

  11. Enantioselectivity in tebuconazole and myclobutanil non-target toxicity and degradation in soils.

    PubMed

    Li, Yuanbo; Dong, Fengshou; Liu, Xingang; Xu, Jun; Han, Yongtao; Zheng, Yongquan

    2015-03-01

    Tebuconazole and myclobutanil are two widely used triazole fungicides, both comprising two enantiomers with different fungicidal activity. However, their non-target toxicity and environmental behavior with respect to enantioselectivity have received limited attention. In the present study, tebuconazole and myclobutanil enantiomers were isolated and used to evaluate the occurrence of enantioselectivity in their acute toxicity to three non-target organisms (Scenedesmus obliquus, Daphnia magna, and Danio rerio). Significant differences were found: R-(-)-tebuconazole was about 1.4-5.9 times more toxic than S-(+)-tebuconazole; rac-myclobutanil was about 1.3-6.1 and 1.4-7.3 more toxic than (-)-myclobutanil and (+)-myclobutanil, respectively. Enantioselectivity was further investigated in terms of fungicide degradation in seven soil samples, which were selected to cover a broad range of soil properties. In aerobic or anaerobic soils, the S-(+)-tebuconazole degraded faster than R-(-)-tebuconazole, and the enantioselectivity showed a correlation with soil organic carbon content. (+)-Myclobutanil was preferentially degraded than (-)-myclobutanil in aerobic soils, whereas both enantiomers degraded at similar rates in anaerobic soils. Apparent correlations of enantioselectivity with soil pH and soil texture were observed for myclobutanil under aerobic conditions. In addition, both fungicides were configurationally stable in soils, i.e., no enantiomerization was found. Enantioselectivity may be a common phenomenon in both aquatic toxicity and biodegradation of chiral triazole fungicides, and this should be considered when assessing ecotoxicological risks of these compounds in the environment.

  12. Propiconazole induces alterations in the hepatic metabolome of mice: relevance to propiconazole-induced hepatocarcinogenesis.

    PubMed

    Nesnow, Stephen; Padgett, William T; Moore, Tanya

    2011-04-01

    Propiconazole is a mouse hepatotumorigenic fungicide and has been the subject of recent investigations into its carcinogenic mechanism of action. The goals of this study were (1) to identify metabolomic changes induced in the liver by increasing doses of propiconazole in mice, (2) to interpret these results with key previously reported biochemical, transcriptomic, and proteomic findings obtained from mouse liver under the same treatment conditions, and (3) to relate these alterations to those associated with the carcinogenesis process. Propiconazole was administered to male CD-1 mice in the feed for 4 days with six mice per feed level (500, 1250, and 2500 ppm). The 2500 ppm dose level had previously been shown to induce both adenocarcinomas and adenomas in mouse liver after a 2-year continuous feed regimen. Endogenous biochemicals were profiled using liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry methods and 261 were detected. The most populous biochemical class detected was lipids, followed by amino acids and then carbohydrates. Nucleotides, cofactors and vitamins, energy, peptides, and xenobiotics were also represented. Of the biochemicals detected, 159 were significantly altered by at least one dose of propiconazole and many showed strong dose responses. Many alterations in the levels of biochemicals were found in the glycogen metabolism, glycolysis, lipolysis, carnitine, and the tricarboxylic acid cycle pathways Several groups of metabolomic responses were ascribed to the metabolism and clearance of propiconazole: glucuronate, glutathione, and cysteine pathways. Groups of metabolic responses supported previous hypotheses on key events that can lead to propiconazole-induced tumorigenesis: oxidative stress and increases in the cholesterol biosynthesis pathway. Groups of metabolomic responses identified biomarkers associated with neoplasia: increases in glycolysis and increases in the levels of spermidine, sarcosine, and

  13. Bioaccumulation and excretion of enantiomers of myclobutanil in Tenebrio molitor larvae through dietary exposure.

    PubMed

    Lv, Xiaotian; Liu, Chen; Li, Yaobin; Gao, Yongxin; Guo, Baoyuan; Wang, Huili; Li, Jianzhong

    2013-12-01

    The bioaccumulation and excretion of enantiomers of myclobutanil in Tenebrio molitor larvae through dietary exposure under laboratory conditions were investigated using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) based on a ChiralcelOD-3R [cellulosetris-tris-(3, 5-dichlorophenyl-carbamate)] column. The wheat bran fed to Tenebrio molitor larvae was spiked with racemic myclobutanil at two dose levels of 20 mg/kg and 2 mg/kg (dry weight). The results showed that there was a significant trend of enantioselective bioaccumulation in the larvae with a preferential accumulation of (-)-myclobutanil in 20 mg/kg dose exposure, but it was not obviously observed in the 2 mg/kg dose group. A kinetic model considering enantiomerization between the two enantiomers based on first-order reactions was built and the rate constants were estimated to discuss the kinetic reason for the different concentrations of individual enantiomers in the larvae. The approximations implied an inversion between the two enantiomers with a relatively higher rate of the inversion from (-)-myclobutanil to (+)-myclobutanil. Meanwhile, analysis of data of excretion samples suggested the active excretion is probably an important pathway for the insect to eliminate myclobutanil rapidly with nonenantioselectivity as a passive transport process, which was consistent with the low accumulation efficiency of myclobutanil measured by BAF (bioaccumulation factor).

  14. PROPICONAZOLE-INDUCED CARCINOGENESIS: ROLE OF OXIDATIVE STRESS

    EPA Science Inventory

    Propiconazole is a systemic foliar fungicide with a broad range of activity. Rodents fed with propiconazole at high dose resulted in diminished body weight, increased liver weight of adults and pups, and eventually liver carcinogenesis. In order to unravel the toxic processes inv...

  15. Effects of myclobutanil on soil microbial biomass, respiration, and soil nitrogen transformations.

    PubMed

    Ju, Chao; Xu, Jun; Wu, Xiaohu; Dong, Fengshou; Liu, Xingang; Zheng, Yongquan

    2016-01-01

    A 3-month-long experiment was conducted to ascertain the effects of different concentrations of myclobutanil (0.4 mg kg(-1) soil [T1]; 1.2 mg kg(-1) soil [T3]; and 4 mg kg(-1) soil [T10]) on soil microbial biomass, respiration, and soil nitrogen transformations using two typical agricultural soils (Henan fluvo-aquic soil and Shanxi cinnamon soil). Soil was sampled after 7, 15, 30, 60, and 90 days of incubation to determine myclobutanil concentration and microbial parameters: soil basal respiration (RB), microbial biomass carbon (MBC) and nitrogen (MBN), NO(-)3-N and NH(+)4-N concentrations, and gene abundance of total bacteria, N2-fixing bacteria, fungi, ammonia-oxidizing archaea (AOA), and ammonia-oxidizing bacteria (AOB). The half-lives of the different doses of myclobutanil varied from 20.3 to 69.3 d in the Henan soil and from 99 to 138.6 d in the Shanxi soil. In the Henan soil, the three treatments caused different degrees of short-term inhibition of RB and MBC, NH(+)4-N, and gene abundance of total bacteria, fungi, N2-fixing bacteria, AOA, and AOB, with the exception of a brief increase in NO(-)3-N content during the T10 treatment. The MBN (immobilized nitrogen) was not affected. In the Shanxi soil, MBC, the populations of total bacteria, fungi, and N2-fixing bacteria, and NH(+)4-N concentration were not significantly affected by myclobutanil. The RB and MBN were decreased transitorily in the T10 treatment. The NO(-)3-N concentrations and the abundance of both AOA and AOB were erratically stimulated by myclobutanil. Regardless of whether stimulation or suppression occurred, the effects of myclobutanil on the two soil types were short term. In summary, myclobutanil had no long-term negative effects on the soil microbial biomass, respiration, and soil nitrogen transformations in the two types of soil, even at 10-fold the recommended dosage.

  16. Interaction of propiconazole in the peanut leafspot disease complex

    SciTech Connect

    Hancock, H.G.

    1985-01-01

    (/sup 14/C)-Propiconazole exhibited characteristics of an apoplastic xenobiotic being acropetally translocated via the transpiration stream to the foliage following root exposure in peanut (Arachis hypogeaea). When applied to leaves, radioactivity was detected distal to the point of application and accumulated along the margins of treated leaves. Redistribution to untreated plant parts was not observed. (/sup 14/C)-propiconazole rapidly penetrated the cuticle of leaves. However, leaves treated with a mixture of (/sup 14/C)-propiconazole and Penetrator 3 exhibited significantly greater foliar uptake of radioactivity than leaves treated with (/sup 14/C)-propiconazole alone. In replicated experiments, leafspot infection (caused by Cercospora arachidicola or Cercosporidium personatum) decreased quadratically with increasing application rate of Tilt 3.6EC (propiconazole) or Vangard 1.0EC (etaconazole). Combinations of fungicide and penetrator 3 gave slightly greater reductions of infection relative to fungicide alone but had no effect on yield. Propiconazole had no effect on the uptake or incorporation of (/sup 14/C)-acetate into the total lipid (TL) of peanut leaf tissue. (/sup 14/C) in the total fatty acids and non-saponifiable lipids was 10 to 20% greater, respectively, in treated tissue relative to the untreated control. Radioactivity of 4-demethyl sterols was up to 57% lower in treated leaves but no differences in radioactivity were detected in 4-methyl and 4,14-dimethyl sterols.

  17. Antifungal polypeptides

    DOEpatents

    Altier, Daniel J.; Ellanskaya, Irina; Ellanskaya, legal representative, Natalia; Gilliam, Jacob T.; Hunter-Cevera, Jennie; Presnail, James K.; Schepers, Eric; Simmons, Carl R.; Torok, Tamas; Yalpani, Nasser

    2009-09-15

    The invention relates to antifungal compositions and methods for protecting a plant from a fungal pathogen. Compositions including antifungal polypeptides isolated from a fungal fermentation broth are provided.

  18. Protein Carbonyl Formation in Response to Propiconazole-Induced Oxidative Stress.

    EPA Science Inventory

    Propiconazole, a widely used fungicide, is hepatotoxic and hepatotumorigenic in mice. Previous genomic analysis of liver tissues from propiconazole-treated mice identified genes and pathways involved in oxidative stress, suggesting that oxidative stress may play a role in propico...

  19. MYCLOBUTANIL AND TRIADIMEFON METHABOLISM BY RAT CYP ISOFORMS AND LIVER MICROSOMES

    EPA Science Inventory


    The mode of action of conazole fungicides is to inhibit cytochrome P450 (CYP) 51 activity and thus the biosynthesis of ergosterol by fungi. Conazoles can also modulate other CYP activities in vertebrate species including humans. Myclobutanil (MCL) and triadimefon (TRD) are ag...

  20. Effects of fungicides triadimefon and propiconazole on soil bacterial communities.

    PubMed

    Yen, Jui-Hung; Chang, Jin-Shu; Huang, Pin-Jui; Wang, Yei-Shung

    2009-09-01

    The impact of fungicides triadimefon and propiconazole on soil bacterial populations from a strawberry field was investigated. Two fungicides were applied to the soil at concentrations of 10 mg/kg or 100 mg/kg with soil water contents 20.2% (fresh soil water content) or 26.0% (field capacity). Changes in bacterial communities were assessed using DNA extraction, polymerase chain reaction (PCR) amplification of the 16S rDNA and denaturing gradient gel electrophoresis (DGGE). High performance liquid chromatography (HPLC) was utilized to detect the residue of fungicides in soils. The results showed that propiconazole was more persistent than triadimefon in soils, and the two soil water contents did not cause significant differences in dissipation rates between the two fungicides. A high concentration of propiconazole could inhibit the existence of soil microbes while one of triadimefon might induce the microbial population in the first stage. From unweighted pair-group method using arithmetic averages (UPGMA) dendrograms, the effect of triadimefon and propiconazole at the two applied concentrations on a soil bacterial community could be long term. After triadimefon was applied for 60 days and propiconazole for 75 days, the compositions of microbial communities were not recovered. From the viewpoint of environmental protection, it was of significant importance to pay more attention not only to the residues of pesticide but also to the change in soil microbial communities.

  1. Occurrence of azoxystrobin, propiconazole, and selected other fungicides in US streams, 2005-2006

    USGS Publications Warehouse

    Battaglin, William A.; Sandstrom, Mark W.; Kuivila, Kathryn M.; Kolpin, Dana W.; Meyer, Michael T.

    2011-01-01

    Fungicides are used to prevent foliar diseases on a wide range of vegetable, field, fruit, and ornamental crops. They are generally more effective as protective rather than curative treatments, and hence tend to be applied before infections take place. Less than 1% of US soybeans were treated with a fungicide in 2002 but by 2006, 4% were treated. Like other pesticides, fungicides can move-off of fields after application and subsequently contaminate surface water, groundwater, and associated sediments. Due to the constant pressure from fungal diseases such as the recent Asian soybean rust outbreak, and the always-present desire to increase crop yields, there is the potential for a significant increase in the amount of fungicides used on US farms. Increased fungicide use could lead to increased environmental concentrations of these compounds. This study documents the occurrence of fungicides in select US streams soon after the first documentation of soybean rust in the US and prior to the corresponding increase in fungicide use to treat this problem. Water samples were collected from 29 streams in 13 states in 2005 and/or 2006, and analyzed for 12 target fungicides. Nine of the 12 fungicides were detected in at least one stream sample and at least one fungicide was detected in 20 of 29 streams. At least one fungicide was detected in 56% of the 103 samples, as many as five fungicides were detected in an individual sample, and mixtures of fungicides were common. Azoxystrobin was detected most frequently (45% of 103 samples) followed by metalaxyl (27%), propiconazole (17%), myclobutanil (9%), and tebuconazole (6%). Fungicide detections ranged from 0.002 to 1.15 μ/L. There was indication of a seasonal pattern to fungicide occurrence, with detections more common and concentrations higher in late summer and early fall than in spring. At a few sites, fungicides were detected in all samples collected suggesting the potential for season-long occurrence in some streams

  2. Biochemical approaches to selective antifungal activity. Focus on azole antifungals.

    PubMed

    Vanden Bossche, H; Marichal, P; Gorrens, J; Coene, M C; Willemsens, G; Bellens, D; Roels, I; Moereels, H; Janssen, P A

    1989-01-01

    Azole antifungals (e.g. the imidazoles: miconazole, clotrimazole, bifonazole, imazalil, ketoconazole, and the triazoles: diniconazole, triadimenol, propiconazole, fluconazole and itraconazole) inhibit in fungal cells the 14 alpha-demethylation of lanosterol or 24-methylenedihydrolanosterol. The consequent inhibition of ergosterol synthesis originates from binding of the unsubstituted nitrogen (N-3 or N-4) of their imidazole or triazole moiety to the heme iron and from binding of their N-1 substituent to the apoprotein of a cytochrome P-450 (P-450(14)DM) of the endoplasmic reticulum. Great differences in both potency and selectivity are found between the different azole antifungals. For example, after 16h of growth of Candida albicans in medium supplemented with [14C]-acetate and increasing concentrations of itraconazole, 100% inhibition of ergosterol synthesis is achieved at 3 x 10(-8) M. Complete inhibition of this synthesis by fluconazole is obtained at 10(-5) M only. The agrochemical imidazole derivative, imazalil, shows high selectivity, it has almost 80 and 98 times more affinity for the Candida P-450(s) than for those of the piglet testes microsomes and bovine adrenal mitochondria, respectively. However, the topically active imidazole antifungal, bifonazole, has the highest affinity for P-450(s) of the testicular microsomes. The triazole antifungal itraconazole inhibits at 10(-5) M the P-450-dependent aromatase by 17.9, whereas 50% inhibition of this enzyme is obtained at about 7.5 x 10(-6)M of the bistriazole derivative fluconazole. The overall results show that both the affinity for the fungal P-450(14)DM and the selectivity are determined by the nitrogen heterocycle and the hydrophobic N-1 substituent of the azole antifungals. The latter has certainly a greater impact. The presence of a triazole and a long hypdrophobic nonligating portion form the basis for itraconazole's potency and selectivity.

  3. Endocrine disrupting effects in vitro of conazole antifungals used as pesticides and pharmaceuticals.

    PubMed

    Kjærstad, Mia B; Taxvig, Camilla; Nellemann, Christine; Vinggaard, Anne Marie; Andersen, Helle R

    2010-12-01

    Widely used conazole antifungals were tested for endocrine disruptive effects using a panel of in vitro assays. They all showed endocrine disrupting potential and ability to act via several different mechanisms. Overall the imidazoles (econazole, ketoconazole, miconazole, prochloraz) were more potent than the triazoles (epoxiconazole, propiconazole, tebuconazole). The critical mechanism seems to be disturbance of steroid biosynthesis. In the H295R cell assay, the conazoles decreased the formation of estradiol and testosterone, and increased the concentration of progesterone, indicating inhibition of enzymes involved in the conversion of progesterone to testosterone. Prochloraz was most potent followed by econazole~miconazole>ketoconazole>tebuconazole>epoxiconazole>propiconazole. In the MCF-7 cell proliferation assay, the conazoles showed anti-estrogenic effect, including aromatase inhibition, since they inhibited the response induced by both 17β-estradiol (miconazole>econazole~ketoconazole>prochloraz>tebuconazole>epoxiconazole>propiconazole) and testosterone (econazole>miconazole>prochloraz>ketoconazole>tebuconazole>epoxiconazole>propiconazole). The triazoles were anti-androgenic in an androgen receptor reporter gene assay (epoxiconazole∼tebuconazole>propiconazole). This effect could not be evaluated for the pharmaceutical imidazoles due to cytotoxicity.

  4. Protein carbonyl formation in response to propiconazole-induced oxidative stress.

    PubMed

    Bruno, Maribel; Moore, Tanya; Nesnow, Stephen; Ge, Yue

    2009-04-01

    Propiconazole, a widely used fungicide, is hepatotoxic and hepatotumorigenic in mice. Previous genomic analysis of liver tissues from propiconazole-treated mice identified genes and pathways involved in oxidative stress, suggesting that oxidative stress may play a role in propiconazole-induced toxicity. To understand the contribution of oxidative stress on toxicity at the protein level, we developed an integrated approach for the systematic measurement of protein oxidation in the livers from propiconazole-treated mice. Liver protein carbonylation increased significantly after treatment with propiconazole, demonstrating propiconazole-associated induction of oxidative stress. Utilizing two-dimensional gel electrophoresis (2-DE), immunoblotting, and mass spectrometry, we identified 17 carbonylated proteins that were altered with varying intensities by propiconazole treatment. The potential effects of protein carbonylation on protein functions and cellular activities in the liver of propiconazole-treated mice were further investigated. A significant negative correlation between protein carbonylation and cytochrome c reductase activity was found. We conclude that glycolysis, mitochondrial respiratory chain, ATP production, amino acid metabolism, CO2 hydration, cellular antioxidant defense and detoxification system, and tetrahydrobiopterin pathways are affected by oxygen radicals in the livers of propiconazole-treated mice. This study suggests a mode of propiconazole-induced toxicity in mouse liver which primarily involves oxidative damage to cellular proteins.

  5. Combined effects of the fungicide propiconazole and agricultural runoff sediments on the aquatic bryophyte Vesicularia dubyana.

    PubMed

    Wu, Qinglan; Riise, Gunnhild; Pflugmacher, Stephan; Greulich, K; Steinberg, Christian E W

    2005-09-01

    Pesticides, firmly attached to the topsoil, might enter nearby watercourses at periods with high erosive loss of sediments. Therefore, exposure of aquatic organisms to these low mobility pesticides, in many cases, will coincide with a high sediment concentration. In this study, both individual and combined effects of propiconazole and runoff sediment on the aquatic model bryophyte Vesicularia dubyana are studied. Individual exposure to propiconazole induced responses in V. dubyana at rather low concentration levels (approximately 1 microg/L), showing that harmful effects of propiconazole potentially may occur in watercourses draining propiconazole-treated fields. Individual exposure to the sediment size fractions S1 (0.16-2 microm) and S2 (0.03-0.16 microm) caused plant stress at a concentration of 100 mg/L. The coarser fraction S1 showed strong inhibition effects on photosynthesis, probably due to light attenuation. Compared to S1, the suspension with the finer fraction S2 showed lower turbidity, higher nutrient content, and a higher proportion of sediment-bound propiconazole. The combined effects of propiconazole and suspended sediment are dependent on concentrations of sediment and propiconazole. At low sediment concentration (e.g., 100 mg/L), neither S1 nor S2 reduce the toxicity of propiconazole, as only 2% of propiconazole are bound to particles. An increase in sediment concentration decreases the bioavailable concentration of propiconazole; however, at the same time, this increases the turbidity, thereby inhibiting plant photosynthesis.

  6. In vivo mutagenicity of conazole fungicides correlates with tumorigenicity

    EPA Science Inventory

    Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. All three conazoles are generally inactive in short-term genotoxicity te...

  7. IN VIVO MUTAGENICITY OF CONAZOLE FUNGICIDES CORRELATES WITH TUMORIGENICITY-JOURNAL

    EPA Science Inventory

    Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. All three conazoles are generally inactive in short-term genotoxicity t...

  8. Altered microRNA expression induced by tumorigenic conazoles in mouse liver.

    EPA Science Inventory

    Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants ...

  9. A microRNA signature for tumorigenic conazoles in mouse liver.

    EPA Science Inventory

    Triadimefon, propiconazole and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants o...

  10. A potential microRNA signature for tumorigenic conazoles in mouse liver

    EPA Science Inventory

    Triadimefon, propiconazole and myclobutanil are conazoles, an important class of agricultural fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants of conazole tumor...

  11. Development of a selective myclobutanil agar (MBA) medium for the isolation of Fusarium species from asparagus fields.

    PubMed

    Vujanovic, Vladimir; Hamel, Chantal; Jabaji-Hare, Suha; St-Arnaud, Marc

    2002-09-01

    A new selective myclobutanil agar medium for the detection of Fusarium, species is proposed. Ten media formulations based on various selective agents (pentachloronitrobenzene (PCNB), Rose Bengal, malachite green, sodium hypochlorite, captan, benomyl, chlorotalonil, myclobutanil, thiram, and cupric sulfate) were compared. First, mycelium growth and colony appearance of Alternaria alternata, Aspergillus flavus, Cladosporium cladosporioides, Epicoccum nigrum, Fusarium sp., Fuisarium solani, Fusarium moniliforme, Fusarium oxysporum f.sp. dianthi, Penicillium sp., and Trichoderma viride isolates were compared. Second, the ability of the different media to isolate and enumerate fusaria from asparagus fields was evaluated. The myclobutanil-based medium showed the highest selectivity to Fusarium spp. growth but required a slightly longer incubation time (>5 d) than peptone-pentachloronitrobenzene-based agar (PPA) (< 5 d). PPA allowed a faster fusaria growth but also permited the growth of other moulds. The other media were less selective and did not allow to isolate fusaria or to differenciate them from other growing fungi.

  12. Cytotoxic effects of propiconazole and its metabolites in mouse and human hepatoma cells and primary mouse hepatocytes

    EPA Science Inventory

    Abstract: Propiconazole is a triazole-containing fungicide that is used agriculturally on grasses, fruits, grains, seeds, hardwoods, and conifers. Propiconazole is a mouse liver hepatotoxicant and a hepatocarcinogen and has adverse reproductive and developmental toxicities in exp...

  13. Laboratory studies on formation of bound residues and degradation of propiconazole in soils.

    PubMed

    Kim, In Seon; Shim, Jae Han; Suh, Yong Tack

    2003-03-01

    Laboratory studies on the formation of bound residues and on the degradation of the triazole fungicide propiconazole were conducted in two different soils. Soils treated with 14C-propiconazole were incubated at 22 degrees C and extracted exhaustively with a solvent at each sampling date until no further propiconazole was extracted. The solvent-extractable residues were used to measure propiconazole remaining in the soil, and the extracted soils were used to investigate bound residues of propiconazole. Mineralization of propiconazole was investigated by measuring [14C]carbon dioxide evolved from the soil samples. Formation of bound residues of propiconazole was higher in silty clay loam soil than in sandy loam soil, giving approximately 38 and 23% of the applied 14C, respectively. In contrast, the rates of degradation and mineralization of propiconazole were lower in silty clay loam soil than in sandy loam soil. Decreased extractability of the 14C residues with incubation time was observed with increased formation of bound residues. When the propiconazole remaining in the solvent-extractable residues was quantitatively measured by high-pressure liquid chromatographic analysis, the half-life value in sandy loam soil was about 315 days, while the half-life in silty clay loam soil exceeded the duration of the 1 year experimental period. Increased formation of bound residues was observed as propiconazole degraded with incubation time, suggesting that degradation products are involved in the formation of bound residues. Our study suggests that the formation of bound residues of propiconazole contributes to the persistence of this fungicide in soil.

  14. Inclusion complex of a new propiconazole derivative with β-cyclodextrin: NMR, ESI–MS and preliminary pharmacological studies

    PubMed Central

    Marangoci, Narcisa; Mares, Mihai; Silion, Mihaela; Fifere, Adrian; Varganici, Cristian; Nicolescu, Alina; Deleanu, Calin; Coroaba, Adina; Pinteala, Mariana; Simionescu, Bogdan C.

    2011-01-01

    A novel inclusion complex of the propiconazole nitrate (NO3PCZ) with β-cyclodextrin (β-CD) was prepared by treatment of propiconazole (PCZ) with an acidic nitrating agent. The formation of NO3PCZ and its inclusion complex with β-CD has been studied by NMR, ESI–MS, TGA, DSC methods. Using the undecoupled signal in the HMBC correlation spectra, almost identical coupling constants of CH from trizolic ring of PCZ and NO3PCZ compounds (1J(HC)3=207 Hz, 1J(CH)5=214 Hz, for PCZ; 1J(HC)3=208 Hz and 1J(CH)5=215 Hz, for NO3PCZ) were determined, confirming that the geometry of the heterocyclic skeleton is identical in both the forms. The 1:1 stoichiometry of the complex was determined by ESI–MS and was confirmed using Scott's equation in DMSO and Higuchi and Connors equation in water. The solubility curve obtained for NO3PCZ in presence of β-CD in distilled water was constructed, resulting in a solubility diagram of AL type. Solubility of NO3PCZ in water was determined by DLS studies. The results showed that NO3PCZ was encapsulated within the β-CD cavity with a binding constant of 330 M-1 in DMSO and 975 M-1 in water. Preliminary pharmacological studies showed higher antifungal activities for NO3PCZ and its inclusion complex, compared with its PCZ analog. The acute toxicity of the complex is smaller than the pure or modified drug, recommending the inclusion complex as future promising therapeutic agents. PMID:25755979

  15. Inclusion complex of a new propiconazole derivative with β-cyclodextrin: NMR, ESI-MS and preliminary pharmacological studies.

    PubMed

    Marangoci, Narcisa; Mares, Mihai; Silion, Mihaela; Fifere, Adrian; Varganici, Cristian; Nicolescu, Alina; Deleanu, Calin; Coroaba, Adina; Pinteala, Mariana; Simionescu, Bogdan C

    2011-05-01

    A novel inclusion complex of the propiconazole nitrate (NO3PCZ) with β-cyclodextrin (β-CD) was prepared by treatment of propiconazole (PCZ) with an acidic nitrating agent. The formation of NO3PCZ and its inclusion complex with β-CD has been studied by NMR, ESI-MS, TGA, DSC methods. Using the undecoupled signal in the HMBC correlation spectra, almost identical coupling constants of CH from trizolic ring of PCZ and NO3PCZ compounds ((1)J(HC)3=207 Hz, (1)J(CH)5=214 Hz, for PCZ; (1)J(HC)3=208 Hz and (1)J(CH)5=215 Hz, for NO3PCZ) were determined, confirming that the geometry of the heterocyclic skeleton is identical in both the forms. The 1:1 stoichiometry of the complex was determined by ESI-MS and was confirmed using Scott's equation in DMSO and Higuchi and Connors equation in water. The solubility curve obtained for NO3PCZ in presence of β-CD in distilled water was constructed, resulting in a solubility diagram of AL type. Solubility of NO3PCZ in water was determined by DLS studies. The results showed that NO3PCZ was encapsulated within the β-CD cavity with a binding constant of 330 M-1 in DMSO and 975 M-1 in water. Preliminary pharmacological studies showed higher antifungal activities for NO3PCZ and its inclusion complex, compared with its PCZ analog. The acute toxicity of the complex is smaller than the pure or modified drug, recommending the inclusion complex as future promising therapeutic agents.

  16. The fungicide propiconazole interferes with embryonic development of the crustacean Daphnia magna.

    PubMed

    Kast-Hutcheson, K; Rider, C V; LeBlanc, G A

    2001-03-01

    Propiconazole is a fungicide used in a variety of agricultural applications. Preliminary studies had suggested that embryos of the crustacean Daphnia magna are particularly susceptible to the toxicity of this chemical. The goals of the present study were to define endpoints of daphnid embryonic development that could be routinely used to assess the embryo toxicity of chemicals and to characterize definitively the embryo toxicity of propiconazole to daphnids. Daphnid embryonic development was characterized into six readily distinguishable stages based on the degree of tissue differentiation. Embryonic development could be monitored either in the brood chamber of the maternal organism or using embryos removed from the brood chamber and incubated ex vivo. Standard toxicity assessment revealed that propiconazole elicited no significant adverse effects on daphnid survival or fecundity during a 21-d exposure to concentrations as high as 0.25 mg/L. Exposure to 0.25 mg/L propiconazole, however, caused a significant incidence of developmental abnormalities and embryonic death. Abnormalities were consistent with developmental arrest at later stages of embryonic maturation. Propiconazole elicited a steep concentration-response curve with respect to embryo toxicity, with a 10% and a 90% incidence of embryo toxicity measured at 0.50 and 0.82 mg/L, respectively. Direct exposure of embryos to propiconazole resulted in toxicity, though the incidence and characteristics of developmental abnormalities were not consistent with that observed during chronic exposures. However, maternal exposure to propiconazole followed by transfer of early embryos to propiconazole-free media resulted in embryo toxicity consistent with that observed during chronic exposure. These results indicate that propiconazole interferes with the later stages of daphnid embryonic development, and that this toxicity is manifested largely via maternal exposure to the fungicide.

  17. Propiconazole inhibits steroidogenesis and reproduction in the fathead minnow (Pimephales promelas)

    EPA Science Inventory

    This study assessed effects of the conazole-fungicide propiconazole on endocrine function and reproductive success of the fathead minnow, using an experimental approach based on previously defined adverse outcome pathways (AOPs) for chemicals that inhibit steroidogenesis in fish...

  18. Propiconazole Enhances Cell Proliferation by Dysregulation of Ras Farnesylation and theMAPK pathway

    EPA Science Inventory

    Previous studies of mice exposed to the hepatotumorigenic fungicide, propiconazole, revealed an increase in hepatic cell proliferation and over-expression of hepatic genes within the cholesterol biosynthesis pathway. Mevalonate, an intermediate in this pathway, has long been a ta...

  19. Size distribution of organic matter and associated propiconazole in agricultural runoff material.

    PubMed

    Wu, Qinglan; Riise, Gunnhild; Kretzschmar, Ruben

    2003-01-01

    Sorption and desorption characteristics of propiconazole (1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole) to different particle/aggregate-size fractions of agricultural runoff material were investigated. Emphasis was put on clay and colloidal size fractions to evaluate their role as potential sorbents and carriers for this pesticide. The runoff material was separated into size fractions ranging from 2 mm to ca. 15 nm by wet sieving, sedimentation, centrifugation, and membrane ultrafiltration. Each fraction was characterized by its organic C content and C/N ratio. Distinctive sorption properties of clay-sized particles and colloids were investigated. The obtained size fractions differed significantly in their organic C concentration, C/N ratio, and sorption properties to propiconazole. Organic matter was mainly associated in aggregates >2 microm. Binding of propiconazole to this coarse fraction made up 80% of the sorbed propiconazole. The distribution coefficient between solid and aqueous phases increased with decreasing particle size. The colloidal fraction (<0.16 microm) exhibited the highest sorbtivity, with a distribution coefficient of 113 L kg(-1), which was more than four times higher than that in the bulk sample (27 L kg(-1)). The fraction <2 microm represented 8% of the total sample weight, but contributed to 20% of the sorbed propiconazole. Strong hysteresis was observed for the sorption-desorption of propiconazole on the runoff material. Under dilution very little sorbed propiconazole will be released into the water phase. Due to its high sorbtivity and mobility and the strong sorption-desorption hysteresis, particles in the fraction <2 microm can be important carriers of propiconazole in runoff suspensions with high sediment load.

  20. [Determination of myclobutanil 25% WG degradation dynamics in ginseng root, stem, leaf and soil by HPLC-MS/MS].

    PubMed

    Wang, Yan; Wang, Chun-Wei; Gao, Jie; Cui, Li-Li; Xu, Yun-Cheng

    2014-07-01

    A high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method was developed for determining degradation dynamics and final residues of myclobutanil 25% WG in ginseng root, stem, leaf and soil. The samples were extracted with acetonitrile, cleaned-up with primary secondary amine (PSA) solid phase extraction cartridge, separated by Kromasil Eternity-5-C18 (2.1 mm x 150 mm, 5 microm) column with a gradient of acetonitrile and 0.1% formate in water as mobile phases, and analyzed with the multiple reaction monitoring (MRM) in positive ion mode by employing the external standard method. The average recoveries and the relative standard derivations (RSDs) of myclobutanil at the spiked level of 0.01-0.20 mg x kg(-1) were 80.9%-90.7% and 5.54%-9.29%, respectively, and the limit of quantification (LOQ) was 0.005 mg x kg(-1). The method with good reproducible, high precision and low detection limit could meet the requirements of residual analysis on ginseng production. The half-lives of myclobutanil were from 6.25 days to 9.94 days in ginseng root, stem, leaf and soil at spraying dosage of 1 152 g x hm(-2) The final residues were below 0.060 1 mg x kg(-1) in root, below 0.081 7 mg x kg(-1) in stem, 0.006 0-0.102 2 mg x kg(-1) in leaf and below 0.037 6 mg x kg(-1) in soil at spraying dosage range from 576 to 1 152 g x hm(-2). It is recommended that the MRLs of myclobutanil in dried ginseng may be suggested to be 0.10 mg x kg(-1) temporarily, and the preharvest interval was set at 35 days.

  1. Propiconazole increases reactive oxygen species levels in mouse hepatic cells in culture and in mouse liver by a cytochrome P450 enzyme mediated process

    EPA Science Inventory

    Propiconazole induces hepatocarcinomas and hepatoadenomas in mice and is a rat liver tumor promoter. Transcriptional, proteomic, metabolomic and biochemical studies of hepatic tissues from mice treated with propiconazole under the conditions of the chronic bioassay indicate that ...

  2. Enantioselective analysis of triazole fungicide myclobutanil in cucumber and soil under different application modes by chiral liquid chromatography/tandem mass spectrometry.

    PubMed

    Dong, Fengshou; Cheng, Li; Liu, Xingang; Xu, Jun; Li, Jing; Li, Yuanbo; Kong, Zhiqiang; Jian, Qiu; Zheng, Yongquan

    2012-02-29

    A sensitive and enantioselective method was developed and validated for the determination of myclobutanil enantiomers by chiral liquid chromatography coupled with tandem mass spectrometry. The separation and determination were performed using reversed-phase chromatography on a Chiralcel OD-RH column, with ACN-water (70/30, v/v) as the mobile phase under isocratic conditions at 0.5 mL/min flow rate. The matrix effect, linearity, precision, accuracy, and stability were evaluated. The proposed method then was successfully applied to the study of enantioselective degradation of rac-myclobutanil in cucumber and soil under different application modes. The results showed that the preferential degradation of (+)-myclobutanil resulted in an enrichment of the (-)-myclobutanil residue in plant and soil. Moreover, in cucumber, the stereoselective intensity of myclobutanil under root douche treatment was stronger than that under foliar spraying treatment, whereas in soil, the intensity was exactly opposite. The probable reasons underlying these enantioselective effects were also discussed. This study highlighted the importance of examining the fate of both enantiomers in the greenhouse system for the correct use of chiral pesticides. PMID:22288843

  3. The oxidative stress response of myclobutanil and cyproconazole on Tetrahymena thermophila.

    PubMed

    Huang, Ai-Guo; Tu, Xiao; Liu, Lei; Wang, Gao-Xue; Ling, Fei

    2016-01-01

    Using Tetrahymena thermophila as experimental models, the oxidative stress of triazole fungicides myclobutanil (MYC) and cyproconazole (CYP) was investigated. Results showed that 24-h EC50 values for MYC and CYP were 16.67 (13.37-19.65) and 20.44 (18.85-21.96) mg/L, respectively; 48-h EC50 values for MYC and CYP were 14.31 (13.13-15.42) and 18.76 (17.09-20.31) mg/L, respectively. Reactive oxygen species was significantly induced and cytotoxicity was caused by MYC and CYP by increasing propidium iodide (PI) fluorescence. Damage of regular wrinkles and appearing of small holes on the cell surface were observed by SEM. Furthermore, MYC and CYP also caused notable changes in enzyme activities and mRNA levels. Overall, the present study points out that MYC and CYP lead to oxidative stress on T. thermophila. The information presented in this study will provide insights into the mechanism of triazoles-induced oxidative stress on T. thermophila.

  4. Propiconazole distribution and effects on Ceratocystis fagacearum survival in roots of treated red oaks.

    PubMed

    Blaedow, Ryan A; Juzwik, Jennifer; Barber, Brian

    2010-10-01

    We investigated the interaction between the oak wilt pathogen (Ceratocystis fagacearum) and propiconazole in lower stems and roots of Quercus rubra to better understand published reports of fungicide failure after 2 years. Propiconazole was infused into mature oaks in July 2004 and roots were inoculated with pathogen endoconidia 1.0 m from injection sites at ±2 weeks of fungicide treatment. Pathogen presence in wood samples was determined by isolation and fungicide concentrations measured using gas chromatography-mass spectrometry. Propiconazole was detected in the roots (≤1.0 m from injection sites) of all treated trees at 2, 12, and 24 months. Propiconazole was detected in all samples (n=68) at 2 and 12 months and in 93% of samples (n=72) at 24 months with concentrations ranging from 815 ppm (12 months in lower stem) to 0.7 ppm (24 months in most distal root segment). Although pathogen isolation incidence was lower in treated than disease control trees at 2 and 12 months, at no time did an infused oak fail to yield the fungus upon isolation. The results document basipetal movement and degradation of propiconazole, as well as the survival of the pathogen, over time in roots and lower stems of infused red oaks.

  5. Some effects of the fungicide propiconazole on cytochrome P450 and glutathione S-transferase in brown trout (Salmo trutta).

    PubMed

    Egaas, E; Sandvik, M; Fjeld, E; Källqvist, T; Goksøyr, A; Svensen, A

    1999-03-01

    The fungicide propiconazole (1-(2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl) -1H-1,2,4-triazole) induced the hepatic cytochrome P4501A (CYP1A) activity towards ethoxyresorufin-O-deethylase (EROD), the content of CYP1A protein as quantified by enzyme-linked immunosorbent assay (ELISA) and the glutathione S-transferase (GST) activity towards the three commonly used substrates CDNB(1-chloro-2,4-dinitrobenzene), cumene hydroperoxide (CU) and ethachrynic acid (EA) in brown trout (Salmo trutta) depending on dose and body weight. An exponential dose response relationship existed between propiconazole exposure and CYP1A activity. A 2. order polynomial regression of the propiconazole concentration (square root transformed) on the data for CDNB, EU and CU revealed a bell-shaped pattern of the GST induction. Reverse-phase HPLC of the GSH-affinity chromatography purified GST isozymes in trout exposed to respectively 8.3, 23, 93, 313 and 606 microg l(-1) propiconazole in the water indicated that the propiconazole treatment may lead to changes in the composition of the subunits compared to the controls. Thus, propiconazole exposure through the water changed the properties of the brown trout hepatic CYP1A and GST, and these changes may be used as a bioindicator on the molecular level of exposure and effect of propiconazole in controlled experiments. The use in monitoring of propiconazole exposure under natural field conditions is possible, however needs further investigation.

  6. In vitro and in vivo evidence for the inhibition of brassinosteroid synthesis by propiconazole through interference with side chain hydroxylation.

    PubMed

    Oh, Keimei; Matsumoto, Tadashi; Hoshi, Tomoki; Yoshizawa, Yuko

    2016-05-01

    We carried out the biochemical evaluation of the target site of propiconazole in BR biosynthesis. Applying BR biosynthesis intermediates to Arabidopsis seedlings grown in the presence of propiconazole under dark condition, we found that the target site of propiconazole in BR biosynthesis can be identified among the C22 and C23 side chain hydroxylation steps from campestanol to teasterone. Using differential spectra techniques to determine the binding affinity of propiconazole to CYP90D1, which is responsible for C23 hydroxylation of BR, we found that propiconazole induced typical type II binding spectra in response to purified recombinant CYP90D1 and the Kd value was found approximately 0.76 μM.

  7. Propiconazole-induced cytochrome P450 gene expression and enzymatic activities in rat and mouse liver.

    PubMed

    Sun, Guobin; Thai, Sheau-Fung; Tully, Douglas B; Lambert, Guy R; Goetz, Amber K; Wolf, Douglas C; Dix, David J; Nesnow, Stephen

    2005-02-15

    Propiconazole is a N-substituted triazole used as a fungicide on fruits, grains, seeds, hardwoods, and conifers. In the present study, propiconazole was examined for its effects on the expression of hepatic cytochrome P450 genes and on the activities of P450 enzymes in male Sprague-Dawley rats and male CD-1 mice. Rats and mice were administered propiconazole by gavage daily for 14 days at doses of 10, 75, and 150 mg/kg body weight/day. Quantitative real time RT-PCR assays of rat hepatic RNA samples from animals treated at the 150 mg/kg body weight/day dose revealed significant mRNA overexpression of the following genes compared to control: CYP1A2 (1.62-fold), CYP2B1 (10.8-fold), CYP3A1/CYP3A23 (2.78-fold), and CYP3A2 (1.84-fold). In mouse liver, propiconazole produced mRNA overexpression of Cyp2b10 (2.39-fold) and Cyp3a11 (5.19-fold). mRNA expression of CYP1A1 was not detected in liver tissues from treated or controls animals from either species. Propiconazole significantly induced both pentoxyresorufin O-dealkylation (PROD) and methoxyresorufin O-dealkylation (MROD) activities in both rat and mouse liver at the 150 mg/kg body weight/day and 75 mg/kg body weight/day doses. In summary, these results indicated that propiconazole induced CYP1A2 in rat liver and CYP2B and CYP3A families of isoforms in rat and mouse liver.

  8. Propiconazole inhibits steroidogenesis and reproduction in the fathead minnow (Pimephales promelas).

    PubMed

    Skolness, Sarah Y; Blanksma, Chad A; Cavallin, Jenna E; Churchill, Jessica J; Durhan, Elizabeth J; Jensen, Kathleen M; Johnson, Rodney D; Kahl, Michael D; Makynen, Elizabeth A; Villeneuve, Daniel L; Ankley, Gerald T

    2013-04-01

    Conazoles are designed to inhibit cytochrome P450 (CYP) 14α-demethylase, an enzyme key to fungal cell wall formation. In vertebrates, conazoles may inhibit other CYPs, potentially disrupting processes like sex steroid synthesis. Propiconazole is a current-use pesticide that is among the first chemicals being tested in the U.S. Environmental Protection Agency endocrine disruptor screening program. Fathead minnows (Pimephales promelas) were exposed to 0, 5, 50, 500, or 1000 µg propiconazole/l in a 21-day study that evaluated apical reproductive endpoints (fecundity, fertility, hatch); measures of endocrine function and steroid synthesis, such as cholesterol, vitellogenin (VTG), and sex steroid (testosterone [T], 17β-estradiol [E2]) concentrations in the plasma; and changes in gonadal expression of steroidogenic genes. Plasma E2 and VTG concentrations in females were reduced by exposure to propiconazole, and egg production was decreased in the 500 and 1000 µg/l treatment groups. These in vivo effects coincided with inhibition of E2 synthesis by ovary explants exposed to propiconazole in vitro. We also observed a compensatory response in females exposed to propiconazole, manifested as increased gonad weight and upregulation of genes coding for key steriodogenic proteins, including CYP19 (aromatase), CYP17 (hydroxylase/lyase), CYP11A (cholesterol side-chain-cleavage), and steroidogenic acute regulatory protein. Other than an increase in relative testis weight, effects on endocrine function in males were less pronounced than in females. This study provides important data relative to the potential endocrine activity of propiconazole in fish and, more generally, to the further delineation of pathways for the reproductive effects of steroid synthesis inhibitors in fish.

  9. P-glycoprotein inhibition by the agricultural pesticide propiconazole and its hydroxylated metabolites: Implications for pesticide-drug interactions.

    PubMed

    Mazur, Christopher S; Marchitti, Satori A; Zastre, Jason

    2015-01-01

    The human efflux transporter P-glycoprotein (P-gp, MDR1) functions as an important cellular defense system against a variety of xenobiotics; however, little information exists on whether environmental chemicals interact with P-gp. Conazoles provide a unique challenge to exposure assessment because of their use as both pesticides and drugs. Propiconazole is an agricultural pesticide undergoing evaluation by the U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program. In this study, the P-gp interaction of propiconazole and its hydroxylated metabolites were evaluated using MDR1-expressing membrane vesicles and NIH-3T3/MDR1 cells. Membrane vesicle assays demonstrated propiconazole (IC50,122.9μM) and its metabolites (IC50s, 350.8μM, 366.4μM, and 456.3μM) inhibited P-gp efflux of a probe substrate, with propiconazole demonstrating the strongest interaction. P-gp mediated transport of propiconazole in MDR1-expressed vesicles was not detected indicating propiconazole interacts with P-gp as an inhibitor rather than a substrate. In NIH-3T3/MDR1 cells, propiconazole (1 and 10μM) led to decreased cellular resistance (chemosensitization) to paclitaxel, a chemotherapeutic drug and known MDR1 substrate. Collectively, these results have pharmacokinetic and risk assessment implications as P-gp interaction may influence pesticide toxicity and the potential for pesticide-drug interactions.

  10. Use of Adverse Outcome Pathways for Assessing Effects of the Fungicide Propiconazole on Fish Reproduction

    EPA Science Inventory

    Adverse outcome pathways (AOP) are used to describe the linkage of biological events from a molecular initiating point, to individual-level-endpoints relevant to risk assessment. This study was done to assess toxicity outcomes for the conazole fungicide propiconazole based on a p...

  11. Proteomic analysis of propiconazole responses in mouse liver: comparison of genomic and proteomic profiles

    EPA Science Inventory

    We have performed for the first time a comprehensive profiling of changes in protein expression of soluble proteins in livers from mice treated with the mouse liver tumorigen, propiconazole, to uncover the pathways and networks altered by this fungicide. Utilizing twodimensional...

  12. Proteomic Analysis of Propiconazole Responses in Mouse Liver-Comparison of Genomic and Proteomic Profiles

    EPA Science Inventory

    We have performed for the first time a comprehensive profiling of changes in protein expression of soluble proteins in livers from mice treated with the mouse liver tumorigen, propiconazole, to uncover the pathways and networks altered by this commonly used fungicide. Utilizing t...

  13. Propiconazole inhibits the sterol 14α-demethylase in Glomus irregulare like in phytopathogenic fungi.

    PubMed

    Calonne, Maryline; Sahraoui, Anissa Lounès-Hadj; Campagnac, Estelle; Debiane, Djouher; Laruelle, Frédéric; Grandmougin-Ferjani, Anne; Fontaine, Joël

    2012-04-01

    The increasing concentrations impact (0.02, 0.2 and 2 mg L(-1)) of a Sterol Biosynthesis Inhibitor (SBI) fungicide, propiconazole, was evaluated on development and sterol metabolism of two non-target organisms: mycorrhizal or non-mycorrhizal transformed chicory roots and the arbuscular mycorrhizal fungus (AMF) Glomus irregulare using monoxenic cultures. In this work, we provide the first evidence of a direct impact of propiconazole on the AMF by disturbing its sterol metabolism. A significant decrease in end-products sterols contents (24-methylcholesterol and in 24-ethylcholesterol) was observed concomitantly to a 24-methylenedihydrolanosterol accumulation indicating the inhibition of a key enzyme in sterol biosynthesis pathway, the sterol 14α-demethylase like in phytopathogenic fungi. A decrease in end-product sterol contents in propiconazole-treated roots was also observed suggesting a slowing down of the sterol metabolism in plant. Taken together, our findings suggest that the inhibition of the both AM symbiotic partners development by propiconazole results from their sterol metabolism alterations.

  14. Defining Adverse Outcome Pathways for Effects of the Fungicide Propiconazole of Fish Reproduction

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are used to describe the linkage of chemical interactions in terms of molecular initiating events to whole organism responses suitable for risk assessment. This study was conducted to develop AOPs for the model fungicide propiconazole relative to r...

  15. What causes the difference in synergistic potentials of propiconazole and prochloraz toward pyrethroids in Daphnia magna?

    PubMed

    Dalhoff, Kristoffer; Gottardi, Michele; Kretschmann, Andreas; Cedergreen, Nina

    2016-03-01

    Azole fungicides (imidazoles and triazoles) are known to function synergistically with several compounds, especially with pyrethroid insecticides, most likely by inhibiting cytochrome P450. Different azole fungicides have been shown to differ in their synergistic potentials usually with the imidazoles being stronger synergists than the triazoles. This study investigated whether the toxicokinetic and toxicodynamic (TKTD) properties of the imidazole prochloraz and triazole propiconazole can explain their different synergistic potential toward the freshwater macroinvertebrate Daphnia magna. Pulse exposure to external concentrations of propiconazole (1.4μM) and prochloraz (1.7μM) for 18h resulted in internal concentrations of 22.7 and 53.5μmolkg(-1)w.w. for propiconazole and prochloraz, respectively. This 2-fold difference in bioaccumulation corresponded very well with the observed 2.7-fold lower external EC50-estimate (7 days) for prochloraz compared to propiconazole. The estimated IC50 for the in vivo inhibition of cytochrome P450 (ECOD) activity, however, measured as transformation of 7-ethoxycoumarin into 7-hydroxycoumarin, was almost 500-fold higher for prochloraz (IC50: 0.011±0.002μM) compared to propiconazole (IC50: 4.9±0.06μM). When indirectly measuring the binding strength of the two azoles, daphnids exposed to propiconazole recovered roughly 80% of their ECOD activity compared to the control shortly after being moved to azole-free medium, indicating that propiconazole causes reversible inhibition of cytochrome P450. In contrast, the ECOD-activity remained inhibited in the prochloraz-exposed daphnids for 12h following transfer to azole-free medium, which correlated with elimination of the measured internal prochloraz concentration (DT95≈13h). These results indicate that lethal toxicity of the azole fungicides is mainly driven by toxicokinetics through their hydrophobicities resulting in different internal concentrations. Their synergistic potential

  16. Dynamics of difenoconazole and propiconazole residues on pomegranate over 2 years under field conditions.

    PubMed

    Mohapatra, Soudamini

    2016-03-01

    Residue dynamics of difenoconazole and propiconazole on pomegranate was studied after application at the recommended and double doses of 125 and 250 g active ingredient (a.i.) ha(-1) during August-October 2012. The study was repeated during the same period in 2013. QuEChERS method, in conjunction with gas chromatography (GC), was used for analysis of the fungicides after carrying out the method validation. The recoveries of the fungicides from pomegranate and soil were between 80.3 and 96.2 %; the limit of detection (LOD) and limit of quantification (LOQ) were 0.016 and 0.05 mg kg(-1), respectively. The uncertainties of measurement were between 9.7 and 16.3 %. The initial residue deposits of difenoconazole were 0.875 and 1.205 mg kg(-1) from treatment at the recommended dose and 1.54 and 1.672 mg kg(-1) from treatment at the double dose from the first- and second-year studies. Propiconazole residues were 0.663 and 0.864 mg kg(-1) from recommended dose treatments and 1.474 and 2.045 mg kg(-1) from double dose treatments from the first- and second-year studies. The half-lives of degradation of difenoconazole were 6.4-8.4 days and propiconazole 7.9-8.5 days over the 2 years. Residues of difenoconazole and propiconazole remained on the pomegranate fruit surface and did not move to the edible part (aril). The pre-harvest intervals (PHIs), the time required for the residues to reduce below their respective EU maximum residue limits (MRLs), were 25.4 and 30.8 days for difenoconazole and 33.3 and 43.8 days for propiconazole from treatments at the recommended and double doses, respectively. Keeping in view consumer safety, the longer PHI from the two studies has been selected.

  17. Sensitivity of Mycosphaerella fijiensis, Causal Agent of Black Sigatoka of Banana, to Propiconazole.

    PubMed

    Romero, R A; Sutton, T B

    1997-01-01

    ABSTRACT One hundred monoascosporic isolates of Mycosphaerella fijiensis were collected in February and November 1994 from each of two banana (Musa spp.) plantations in Costa Rica. Locations at San Pablo and Coopecariari had been sprayed with propiconazole for the past 7 years to control black Sigatoka. One hundred monoascosporic isolates from a third location, San Carlos, with no history of fungicide use, also were tested for sensitivity to propiconazole. Fifty percent effective concentration (EC(50)) values were calculated for individual isolates by regressing the relative inhibition of colony growth against the natural logarithm of the fungicide concentration. In the February sample, the mean EC(50) values for San Pablo and Coopecariari populations were 0.06 and 0.05 mug a.i. ml(-1), respectively, which were not statistically different (P = 0.05). The mean EC(50) value of the population at San Carlos was 0.008 mug a.i. ml(-1), which was significantly lower (P = 0.001) than the mean EC(50) values obtained at San Pablo and Coopecariari. Frequency distributions of EC(50) values of isolates from the three populations collected in February showed that 80% of isolates from San Pablo and Coopecariari had EC(50) values greater than the highest EC(50) value from San Carlos, indicating a significant shift in reduced sensitivity to propiconazole. Isolates collected in November 1994, after eight treatments of propiconazole at San Pablo and Coopecariari, showed a significant increase in mean EC(50) values compared with the means observed in February. The high proportion of isolates with reduced sensitivity to propiconazole may account for the unsatisfactory control of black Sigatoka between 1992 and 1993 in the two banana plantations at San Pablo and Coopecariari.

  18. Development and application of quantitative methods for monitoring dermal and inhalation exposure to propiconazole.

    PubMed

    Flack, Sheila; Goktepe, Ipek; Ball, Louise M; Nylander-French, Leena A

    2008-03-01

    Quantitative methods to measure dermal and inhalation exposure to the fungicide propiconazole were developed in the laboratory and applied in the occupational exposure setting for monitoring five farm workers' exposure during pesticide preparation and application to peach crops. Dermal exposure was measured with tape-strips applied to the skin, and the amount of propiconazole was normalized to keratin content in the tape-strip. Inhalation exposure was measured with an OVS tube placed in the worker's breathing-zone during pesticide handling. Samples were analyzed by GC-MS in EI+ mode (limit of detection 6 pg microl(-1)). Dermal exposure ranged from non-detectable to 32.1 +/- 22.6 ng per microg keratin while breathing-zone concentrations varied from 0.2 to 2.2 microg m(-3). A positive correlation was observed between breathing-zone concentrations and ambient air temperature (r2 = 0.87, p < 0.01). Breathing-zone concentrations did not correlate with dermal exposure levels (r2 = 0.11, p = 0.52). Propiconazole levels were below limit of detection when rubber gloves, coveralls, and full-face mask were used. The total-body propiconazole dose, determined for each worker by summing the estimated dermal dose and inhalation dose, ranged from 0.01 to 12 microg per kg body weight per day. Our results show that tape-stripping of the skin and the OVS can be effectively utilized to measure dermal and inhalation exposure to propiconazole, respectively, and that the dermal route of exposure contributed substantially more to the total dose than the inhalation route.

  19. Short-term effects of propiconazole on hypothalamic-pituitary-gonadal function in the fathead minnows (Pimephales promelas)

    EPA Science Inventory

    Propiconazole is an ergosterol inhibitor commonly used in agriculture and has been detected in aquatic environments. Ergosterol inhibitors decrease fungal growth through effects on 14á-demethylase, a cytochrome P450 (CYP), isoform important for ergosterol biosynthesis. In higher ...

  20. Cytotoxic effects of propiconazole and its metabolites in mouse and human hepatoma cells and primary mouse hepatocytes.

    PubMed

    Chen, Pei-Jen; Moore, Tanya; Nesnow, Stephen

    2008-09-01

    Propiconazole is a triazole-containing fungicide that is used agriculturally on grasses, fruits, grains, seeds, hardwoods, and conifers. Propiconazole is a mouse liver hepatotoxicant and a hepatocarcinogen that has adverse reproductive and developmental toxicities in experimental animals. The goal of this study was to investigate the cytotoxic responses of propiconazole and its metabolites to determine if metabolism of this agent differentially affected its cytotoxic activities in hepatic tumor cell lines and in primary hepatocytes. To this end the cytotoxic effects of propiconazole and five of its metabolites were examined in three hepatic cell types: The mouse hepatoma Hepa1c1c7 cell line, the human hepatoma HepG2 cell line, and primary cultures of mouse hepatocytes. We initially compared the responses of propiconazole exposure in both Hepa1c1c7 and HepG2 cell lines over a concentration range of 0-200 microM using two assay systems: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the neutral red assay. Concentration-related cytotoxic responses were evident in both cell lines using both endpoints with the MTT assay providing enhanced sensitivity. The relative cytotoxic effects of propiconazole and five propiconazole metabolites were further assessed by the MTT assay using Hepa1c1c7 and HepG2 tumor cell lines. The cell cultures were exposed to various concentrations of propiconazole and five of its metabolites over a range of 0-400 microM. Propiconazole was cytotoxic in both cell lines in a dose-dependent manner. All five metabolites were less cytotoxic in both cell lines compared to the parent compound. The most cytotoxic metabolites in Hepa1c1c7 and HepG2 cells among the five were 3-(2-((1H-1,2,4-triazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)propan-1-ol and 1-(2-((1H-1,2,4-triazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)propan-2-ol. Propiconazole was cytotoxic in primary mouse hepatocytes; however

  1. Propiconazole increases reactive oxygen species levels in mouse hepatic cells in culture and in mouse liver by a cytochrome P450 enzyme mediated process.

    PubMed

    Nesnow, Stephen; Grindstaff, Rachel D; Lambert, Guy; Padgett, William T; Bruno, Maribel; Ge, Yue; Chen, Pei-Jen; Wood, Charles E; Murphy, Lynea

    2011-10-15

    Propiconazole induces hepatocellular carcinomas and hepatocellular adenomas in mice and promotes liver tumors in rats. Transcriptional, proteomic, metabolomic and biochemical studies of hepatic tissues from mice treated with propiconazole under the conditions of the chronic bioassay indicated that propiconazole induced oxidative stress. Here we sought to identify the source of the reactive oxygen species (ROS) induced by propiconazole using both AML12 immortalized mouse hepatocytes in culture and liver tissues from mice. We also sought to further characterize the nature and effects of ROS formation induced by propiconazole treatment in mouse liver. ROS was induced in AML12 cells by propiconazole as measured by fluorescence detection and its formation was ameliorated by N-acetylcysteine. Propiconazole induced glutathione-S-transferase (GSTα) protein levels and increased the levels of thiobarbituric acid reactive substances (TBARS) in AML12 cells. The TBARS levels were decreased by diphenylene iodonium chloride (DPIC), a cytochrome P450 (CYP) reductase inhibitor revealing the role of CYPs in ROS generation. It has been previously reported that Cyp2b and Cyp3a proteins were induced in mouse liver by propiconazole and that Cyp2b and Cyp3a proteins undergo uncoupling of their CYP catalytic cycle releasing ROS. Therefore, salicylic acid hydroxylation was used as probe for ROS formation using microsomes from mice treated with propiconazole. These studies showed that levels of 2,3-dihydroxybenzoic acid (an ROS derived metabolite) were decreased by ketoconazole, melatonin and DPIC. In vivo, propiconazole increased hepatic malondialdehyde levels and GSTα protein levels and had no effect on hepatic catalase or superoxide dismutase activities. Based on these observations we conclude that propiconazole induces ROS in mouse liver by increasing CYP protein levels leading to increased ROS levels. Our data also suggest that propiconazole induces the hydroxyl radical as a major

  2. Effect of turfgrass cover and irrigation on soil mobility and dissipation of mefenoxam and propiconazole.

    PubMed

    Gardner, D S; Branham, B E

    2001-01-01

    Irrigation effects on pesticide mobility have been studied, but few direct comparisons of pesticide mobility or persistence have been conducted on turfgrass versus bare soil. The interaction of irrigation practices and the presence of turfgrass on the mobility and dissipation of mefenoxam [N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-D-alanine methyl ester] and propiconazole (1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole) was studied. Sampling cylinders (20-cm diam.) were placed in either creeping bentgrass [Agrostis stolonifera L. var. palustris (Huds.) Farw.] or bare soil. Mefenoxam was applied at 770 g a.i. ha(-1) and propiconazole was applied at 1540 g a.i. ha(-1) on 14 June 1999. Sampling cylinders were removed 2 h after treatment and 4,8,16, 32, and 64 days after treatment (DAT) and the cores were sectioned by depth. Dissipation of mefenoxam was rapid, regardless of the amount of surface organic matter or irrigation. The half-life (t1/2) of mefenoxam was 5 to 6 d in turf and 7 to 8 d in bare soil. Most mefenoxam residues found in soil under turfgrass were in the 0- to 1-cm section at 0, 4, and 8 DAT. Residues were found in the 15- to 30-cm section at 4, 8, 16, 32, and 64 DAT, regardless of turf cover or irrigation. The t1/2 of propiconazole was 12 to 15 d in turfgrass and 29 d in bare soil. Little movement of propiconazole was observed in either bare soil or turf.

  3. On-line preconcentration and chiral separation of propiconazole by cyclodextrin-modified micellar electrokinetic chromatography.

    PubMed

    Wan Ibrahim, Wan Aini; Hermawan, Dadan; Sanagi, Mohd Marsin

    2007-11-01

    A method for the chiral separation of propiconazole using cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) with hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) as chiral selector is reported. The use of a mixture of 30 mM HP-gamma-CD, 50mM SDS, methanol-acetonitrile 10%:5% (v/v) in 25 mM phosphate buffer solution was able to separate two enantiomeric pairs of propiconazole. Stacking- and sweeping-CD-MEKC under neutral pH (pH 7) and under acidic condition (pH 3.0) were used as two on-line preconcentration methods to increase detection sensitivity of propiconazole. Good repeatabilities in the migration time, peak area and peak height were obtained in terms of relative standard deviation (RSD). A sensitivity enhancement factor of 100-fold was achieved using sweeping-CD-MEKC at acidic pH. This is the first report on the separation of two pairs of propiconazole enantiomers and all the enantiomers of fenbuconazole and tebuconazole using sweeping-CD-MEKC. The limit of detection (S/N=3) for the three triazole fungicides ranged from 0.09 to 0.1 microg/mL, which is well below the maximum residue limits (MRL) set by Codex Alimentarius Commission (CAC). Combination of solid-phase extraction (SPE) pretreatment and sweeping-CD-MEKC procedure was applied to the determination of selected triazole fungicides in grapes samples spiked at concentration 10-40 times lower than the MRL established by the CAC. The average recoveries of the selected fungicides in spiked grapes samples were good, ranging from 73% to 109% with RSD of 9-12% (n=3).

  4. The dissipation of tebuconazole and propiconazole in boronia (Boronia megastigma Nees).

    PubMed

    Garland, Sandra M; Davies, Noel W; Menary, Robert C

    2004-10-01

    The broad spectrum, systemic fungicides tebuconazole and propiconazole are used to control rust in boronia (Boronia megastigma Nees). Gas chromatography combined with either a benchtop quadrupole mass spectrometer or a high-resolution mass spectrometer allowed for the monitoring of both pesticides in boronia leaves, flowers, and concrete. Field trials were established at two sites to determine the rate of dissipation of tebuconazole and propiconazole in boronia. At site 1, two application rates of 125 and 250 g active ingredient/hectare (ai/ha) tebuconazole were employed. Treatments were repeated 17 days later. At harvest, 286 days after the final application, tebuconazole was detected at levels of 0.06 +/- 0.05 and 0.5 +/- 0.1 [mg/kg +/- standard error, on a dry matter basis (DMB)] in the leaves collected from plots treated with 125 and 250 g ai/ha of tebuconazole, respectively. The oil produced from the flowers collected at the final harvest had residues of tebuconazole at levels of 0.06 +/- 0.03 and 0.10 +/- 0.08 mg/kg for the 125 and 250 g ai/ha application rates, respectively. Two repeat applications of 125 g ai/ha propiconazole were also used at site 1. Residues of propiconazole were detected at 0.09 +/- 0.03 mg/kg (DMB) 286 days after the final application. At site 2, treatments of 125 g ai/ha of tebuconazole were applied twice. At harvest, 279 days after the final application of tebuconazole, residues were recorded at 0.30 +/- 0.09 mg/kg in the leaves (DMB) while the oil produced had 0.20 +/- 0.07 mg/kg.

  5. Laboratory degradation studies of bentazone, dichlorprop, MCPA, and propiconazole in Norwegian soils.

    PubMed

    Thorstensen, C W; Lode, O

    2001-01-01

    Laboratory degradation studies were performed in Norwegian soils using two commercial formulations (Tilt and Triagran-P) containing either propiconazole alone or a combination of bentazone, dichlorprop, and MCPA. These soils included a fine sandy loam from Hole and a loam from Kroer, both of which are representative of Norwegian agricultural soils. The third soil was a highly decomposed organic material from the Froland forest. A fourth soil from the Skuterud watershed was used only for propiconazole degradation. After 84 d, less than 0.1% of the initial MCPA concentration remained in all three selected soils. For dichlorprop, the same results were found for the fine sandy loam and the organic-rich soil, but in the loam, 26% of the initial concentration remained. After 84 d, less than 0.1% of the initial concentration of bentazone remained in the organic-rich soil, but in the loam and the fine sandy loam 52 and 69% remained, respectively. Propiconazole was shown to be different from the other pesticides by its persistence. Amounts of initial concentration remaining varied from 40, 70, and 82% in the reference soils after 84 d for the organic-rich soil, fine sandy loam, and loam, respectively. The organic-rich soil showed the highest capacity to decompose all four pesticides. The results from the agricultural soils and the Skuterud watershed showed that the persistence of propiconazole was high. Pesticide degradation was approximated to first-order kinetics. Slow rates of degradation, where more than 50% of the pesticide remained in the soil after the 84-d duration of the experiment, did not fit well with first-order kinetics.

  6. Sorption of bentazone, dichlorprop, MCPA, and propiconazole in reference soils from Norway.

    PubMed

    Thorstensen, C W; Lode, O; Eklo, O M; Christiansen, A

    2001-01-01

    Sorption-desorption kinetic and isotherm studies were performed by the batch equilibrium technique in three Norwegian soils. The soils were a fine sandy loam, a loam, and a soil of highly decomposed organic material. Two commercially formulations were used, Triagran-P and Tilt, containing either a mixture of bentazone [3-isopropyl-1H-2, 1,3-benzothiadiazin-4(3H)-one 2,2-dioxide], dichlorprop [(R)-2-(2, 4-dichlorophenoxy)-propionic acid], and MCPA [(4-chloro-2-methylphenoxy)acetic acid], or propiconazole [(+/-)1-(2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl)-1H-1,2,4-triazole] alone. Sorption-desorption equilibrium occurred within 10 h for all pesticides. The Freundlich isotherms indicated nonlinear sorption of bentazone, dichlorprop, MCPA, and propiconazole. For all pesticides the highest Freundlich adsorption coefficient (K(F)) values were in the soil with highest organic content and lowest pH. For the fine sandy loam and loam, which are representative Norwegian agricultural soils, the results indicate that bentazone, dichlorprop, and MCPA are mobile with KF values ranging from 0.07 to 1.50 mg1-1/n kg(-1) L1/n. Propiconazole is much less mobile with KF values ranging from 27.00 to 36.02 mg1-1/n kg(-1) L1/n in the agricultural soils.

  7. Early life exposure to a rodent carcinogen propiconazole fungicide induces oxidative stress and hepatocarcinogenesis in medaka fish.

    PubMed

    Tu, Tzu-Yi; Hong, Chwan-Yang; Sasado, Takao; Kashiwada, Shosaku; Chen, Pei-Jen

    2016-01-01

    Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53(-/-) mutant of medaka fish (Oryzias latipes) to propiconazole (2.5-250μg/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53(-/-) mutant medaka with early life exposure to propiconazole showed increased incidence of hepatocarcionogensis, as compared to the p53(-/-) control group and wild type strain. We demonstrated that propiconazole can initiate ROS-mediated oxidative stress and induce hepatic tumorigenesis associated with CYP1A- and/or p53 -mediated pathways with the use of wild type and p53(-/-) mutant of medaka fish. The toxic response of medaka to propiconazole is compatible with that observed in rodents. PMID:26619215

  8. Early life exposure to a rodent carcinogen propiconazole fungicide induces oxidative stress and hepatocarcinogenesis in medaka fish.

    PubMed

    Tu, Tzu-Yi; Hong, Chwan-Yang; Sasado, Takao; Kashiwada, Shosaku; Chen, Pei-Jen

    2016-01-01

    Conazole pollution is an emerging concern to human health and environmental safety because of the broad use of conazole fungicides in agriculture and medicine and their frequent occurrence in aquifers. The agricultural pesticide propiconazole has received much regulatory interest because it is a known rodent carcinogen with evidence of multiple adverse effects in mammals and non-targeted organisms. However, the carcinogenic effect and associated mechanism of propiconazole in fish under microgram-per-liter levels of environmental-relevant exposure remains unclear. To explore whether early life of propiconzaole exposure would induce oxidative stress and latent carcinogenic effects in fish, we continuously exposed larvae of wild type or p53(-/-) mutant of medaka fish (Oryzias latipes) to propiconazole (2.5-250μg/L) for 3, 7, 14 or 28 days and assessed liver histopathology and/or the oxidative stress response and gene expression during exposure and throughout adulthood. Propiconazole dose-dependently induced reactive oxygen species (ROS) level, altered homeostasis of antioxidant superoxide dismutase, catalase and glutathione S-transferase and caused lipid and protein peroxidation during early life exposure in wild type medaka. Such exposure also significantly upregulated gene expression of the cytochrome P450 CYP1A, but marginally suppressed that of tumor suppressor p53 in adults. Furthermore, histopathology revealed that p53(-/-) mutant medaka with early life exposure to propiconazole showed increased incidence of hepatocarcionogensis, as compared to the p53(-/-) control group and wild type strain. We demonstrated that propiconazole can initiate ROS-mediated oxidative stress and induce hepatic tumorigenesis associated with CYP1A- and/or p53 -mediated pathways with the use of wild type and p53(-/-) mutant of medaka fish. The toxic response of medaka to propiconazole is compatible with that observed in rodents.

  9. Antifungal nanoparticles and surfaces.

    PubMed

    Paulo, Cristiana S O; Vidal, Maria; Ferreira, Lino S

    2010-10-11

    Nosocomial fungal infections, an increasing healthcare concern worldwide, are often associated with medical devices. We have developed antifungal nanoparticle conjugates that can act in suspension or attach to a surface, efficiently killing fungi. For that purpose, we immobilized covalently amphotericin B (AmB), a potent antifungal agent approved by the FDA, widely used in clinical practice and effective against a large spectrum of fungi, into silica nanoparticles. These antifungal nanoparticle conjugates are fungicidal against several strains of Candida sp., mainly by contact. In addition, they can be reused up to 5 cycles without losing their activity. Our results show that the antifungal nanoparticle conjugates are more fungistatic and fungicidal than 10 nm colloidal silver. The antifungal activity of the antifungal nanoparticle conjugates is maintained when they are immobilized on a surface using a chemical adhesive formed by polydopamine. The antifungal nanocoatings have no hemolytic or cytotoxic effect against red blood cells and blood mononuclear cells, respectively. Surfaces coated with these antifungal nanoparticle conjugates can be very useful to render medical devices with antifungal properties. PMID:20845938

  10. Proteomic analysis of propiconazole responses in mouse liver: comparison of genomic and proteomic profiles.

    PubMed

    Ortiz, Pedro A; Bruno, Maribel E; Moore, Tanya; Nesnow, Stephen; Winnik, Witold; Ge, Yue

    2010-03-01

    We have performed for the first time a comprehensive profiling of changes in protein expression of soluble proteins in livers from mice treated with the mouse liver tumorigen, propiconazole, to uncover the pathways and networks altered by this fungicide. Utilizing two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), we identified 62 proteins that were altered. Several of these protein changes detected by 2-DE/MS were verified by Western blot analyses. These differentially expressed proteins were mapped using Ingenuity Pathway Analyses (IPA) canonical pathways and IPA tox lists. Forty-four pathways/lists were identified. IPA was also used to create networks of interacting protein clusters. The protein-generated IPA canonical pathways and IPA tox lists were compared to those pathways and lists previously generated from genomic analyses from livers of mice treated with propiconazole under the same experimental conditions. There was a significant overlap in the specific pathways and lists generated from the proteomic and the genomic data with 27 pathways common to both proteomic and genomic analyses. However, there were also 17 pathways/lists identified only by proteomics analysis and 21 pathways/lists only identified by genomic analysis. The protein network analysis produced interacting subnetworks centered around hepatocyte nuclear factor 4 alpha (HNF4 alpha), MYC, proteasome subunit type 4 alpha, and glutathione S-transferase (GST). The HNF4 alpha network hub was also identified by genomic analysis. Five GST isoforms were identified by proteomic analysis and GSTs were present in 10 of the 44 protein-based pathways/lists. Hepatic GST activities were compared between mice treated with propiconazole and 2 additional conazoles and higher GST activities were found to be associated with the tumorigenic conazoles. Overall, this comparative proteomic and genomic study has revealed a series of alterations in livers induced by propiconazole: nuclear receptor

  11. Side effects of the sterol biosynthesis inhibitor fungicide, propiconazole, on a beneficial arbuscular mycorrhizal fungus.

    PubMed

    Calonne, M; Fontaine, J; Debiane, D; Laruelle, F; Grandmougin, A; Lounes-Hadj Sahraoui, A

    2011-01-01

    The Sterol Biosynthesis Inhibitor (SBI) fungicide, propiconazole, is extensively used in modern agriculture to control fungal diseases. Unfortunately, little is known about its potential side effects on non-target plant-beneficial soil organisms such as arbuscular mycorrhizal fungi (AMF). The direct impact of increasing propiconazole concentrations (0.02; 0.2 and 2 mg x L(-1)) on the lipid metabolism of the AMF Glomus irregulare in relation with its development, was studied by using axenic cultures. The propiconazole impact on G. irregulare was investigated, firstly, through sterol (the target-metabolism of SBI fungicides), phospholipids (PL) and their associated fatty acids (PLFA) analysis (the main membrane components) and secondly by measuring malondialdehyde (MDA) (a biomarker of lipid peroxidation) formation. Finally, the storage lipid quantity, triacylglycerol (TAG), was quantified. Our results demonstrated that the drastic reduction of G. irregulare development (germination, germ tube elongation, colonization, extraradical hyphae growth and sporulation) could be explained not only by the decreases of the total sterol end-products (24-methylcholesterol and 24-ethylcholesterol) and by 24-methylene dihydrolanosterol (a sterol precursor) accumulation, suggesting an inhibition of a key enzyme in sterol biosynthesis pathway (14alpha-demethylase), but also by the increases in phosphatidylcholine (PC) and PLFA (C16:0; C18:0 and C18:3) quantities as well as by MDA accumulation. Moreover, TAG quantity was found to be reduced in the presence of propiconazole, suggesting their use by G. irregulare in a response to propiconazole toxicity. In conclusion, taken together, the findings of the current study highlighted a relationship between the SBI fungicide toxicity against the beneficial AMF G. irregulare and (1) the disturbance in the sterol metabolism, (2) the membrane alteration (PC decrease, lipid peroxidation) as well as (3) the reduction in storage lipids, TAG. More

  12. Propiconazole enhanced hepatic cell proliferation is associated with dysregulation of the cholesterol biosynthesis pathway leading to activation of Erk1/2 through Ras famesylation

    EPA Science Inventory

    Propiconazole is a mouse hepatotumorigenic fungicide designed to inhibit CYP51, a key enzyme in the biosynthesis of ergosterol in fungi and is widely used in agriculture to prevent fungal growth. Metabolomic studies in mice revealed that propiconazole increased levels of hepatic ...

  13. Loss of Propiconazole and its Four Stereoisomers from the Water Phase of Two Soil-Water Slurries as Measured by Capillary Electrophoresis

    EPA Science Inventory

    Propiconazole is a chiral fungicide used in agriculture for control of many fungal diseases on a variety of crops. This use provides opportunities for pollution of soil and, subsequently, groundwater. The rate of loss of propiconazole from the water phase of two different soil-wa...

  14. Dissipation of propiconazole and tebuconazole in peppermint crops (Mentha piperita (Labiatae)) and their residues in distilled oils.

    PubMed

    Garland, S M; Menary, R C; Davies, N W

    1999-01-01

    The broad-spectrum, systemic fungicides propiconazole (1) and tebuconazole (2) are used to control rust in peppermint (Mentha piperita L.). An analytical method, using gas chromatography combined with detection by high-resolution mass spectrometry, was developed to allow for the simultaneous monitoring of both pesticides in peppermint leaves and oil. Field trials were established to determine the rate of dissipation of tebuconazole and propiconazole in peppermint crops. Three applications of each fungicide were trialed at two rates (125 and 250 g of active ingredient (ai)/ha). At harvest, 64 days after the final application, propiconazole was detected at levels of 0.06 mg/kg and 0.09 mg/kg of dry weight, and tebuconazole was detected at 0.26 and 0.80 mg/kg dry weight, in identical trials. Rates of dissipation of propiconazole and tebuconazole were lower at a second trial site, where three applications of 125 g/ha ai for each fungicide resulted in residue levels of 0.21 mg/kg for both pesticides, detected 89 days after the last application. Propiconazole and tebuconazole were detected in the distilled oil at levels between 0.02 and 0.05 mg/kg and between 0.011 and 0.041 mg/kg, respectively. Propiconazole had a higher tendency to co-distill with the peppermint oil, with 0.7% of that present in the vegetative material ending up in the oil, compared to 0.09% of tebuconazole.

  15. Antifungal compounds from cyanobacteria.

    PubMed

    Shishido, Tânia K; Humisto, Anu; Jokela, Jouni; Liu, Liwei; Wahlsten, Matti; Tamrakar, Anisha; Fewer, David P; Permi, Perttu; Andreote, Ana P D; Fiore, Marli F; Sivonen, Kaarina

    2015-04-13

    Cyanobacteria are photosynthetic prokaryotes found in a range of environments. They are infamous for the production of toxins, as well as bioactive compounds, which exhibit anticancer, antimicrobial and protease inhibition activities. Cyanobacteria produce a broad range of antifungals belonging to structural classes, such as peptides, polyketides and alkaloids. Here, we tested cyanobacteria from a wide variety of environments for antifungal activity. The potent antifungal macrolide scytophycin was detected in Anabaena sp. HAN21/1, Anabaena cf. cylindrica PH133, Nostoc sp. HAN11/1 and Scytonema sp. HAN3/2. To our knowledge, this is the first description of Anabaena strains that produce scytophycins. We detected antifungal glycolipopeptide hassallidin production in Anabaena spp. BIR JV1 and HAN7/1 and in Nostoc spp. 6sf Calc and CENA 219. These strains were isolated from brackish and freshwater samples collected in Brazil, the Czech Republic and Finland. In addition, three cyanobacterial strains, Fischerella sp. CENA 298, Scytonema hofmanni PCC 7110 and Nostoc sp. N107.3, produced unidentified antifungal compounds that warrant further characterization. Interestingly, all of the strains shown to produce antifungal compounds in this study belong to Nostocales or Stigonematales cyanobacterial orders.

  16. Antifungal Compounds from Cyanobacteria

    PubMed Central

    Shishido, Tânia K.; Humisto, Anu; Jokela, Jouni; Liu, Liwei; Wahlsten, Matti; Tamrakar, Anisha; Fewer, David P.; Permi, Perttu; Andreote, Ana P. D.; Fiore, Marli F.; Sivonen, Kaarina

    2015-01-01

    Cyanobacteria are photosynthetic prokaryotes found in a range of environments. They are infamous for the production of toxins, as well as bioactive compounds, which exhibit anticancer, antimicrobial and protease inhibition activities. Cyanobacteria produce a broad range of antifungals belonging to structural classes, such as peptides, polyketides and alkaloids. Here, we tested cyanobacteria from a wide variety of environments for antifungal activity. The potent antifungal macrolide scytophycin was detected in Anabaena sp. HAN21/1, Anabaena cf. cylindrica PH133, Nostoc sp. HAN11/1 and Scytonema sp. HAN3/2. To our knowledge, this is the first description of Anabaena strains that produce scytophycins. We detected antifungal glycolipopeptide hassallidin production in Anabaena spp. BIR JV1 and HAN7/1 and in Nostoc spp. 6sf Calc and CENA 219. These strains were isolated from brackish and freshwater samples collected in Brazil, the Czech Republic and Finland. In addition, three cyanobacterial strains, Fischerella sp. CENA 298, Scytonema hofmanni PCC 7110 and Nostoc sp. N107.3, produced unidentified antifungal compounds that warrant further characterization. Interestingly, all of the strains shown to produce antifungal compounds in this study belong to Nostocales or Stigonematales cyanobacterial orders. PMID:25871291

  17. Evaluation of the reproductive toxicity of fungicide propiconazole in male rats.

    PubMed

    Costa, Nathália Orlandini; Vieira, Milene Leivas; Sgarioni, Vanessa; Pereira, Marina Rangel F; Montagnini, Bruno Garcia; Mesquita, Suzana de Fátima Paccola; Gerardin, Daniela Cristina Ceccatto

    2015-09-01

    The propiconazole (Prop) is a fungicide extensively used in agriculture. There are evidences that this compound may cause endocrine disrupting effects. In vitro studies have demonstrated that Prop inhibits the activity of CYP 19 (aromatase), responsible for converting androgens into estrogens and also is an androgen and estrogen receptor antagonist. Therefore, this study evaluated the reproductive toxicity of Prop treatment in male rats. The Wistar rats were divided in three groups and were treated daily, by gavage, with corn oil (control group), propiconazole 4 mg/kg (Prop 4) and 20 mg/kg (Prop 20), from post-natal day 50 to 120. The following were observed: the body weight gain, sexual behavior, testosterone and estradiol plasmatic levels, organs weight, sperm count and morphology and testicular histomorphology. There was an increase in abnormal tail morphology sperm, seminal vesicle and vas deferens weight, and a decrease in estradiol levels in Prop 4 group. Sexual behavior was affected only in the Prop 20 group. These results suggest that Prop treatment induced alterations in some reproductive parameters, what could be related with an endocrine disruption.

  18. Fate and transport of agriculturally applied fungicidal compounds, azoxystrobin and propiconazole.

    PubMed

    Edwards, Paul G; Murphy, Tracye M; Lydy, Michael J

    2016-03-01

    Fungicidal active ingredients azoxystrobin and propiconazole, individually and in combination, have been marketed worldwide in a range of fungicide treatment products for preventative and curative purposes, respectively. Their presence in streams located throughout the midwestern and southeastern United States warrant the need for research into the potential routes of transport of these fungicides in an agricultural field setting. Potential canopy penetration and drift effects of these fungicides during aerial and ground applications were studied in the current project. Canopy penetration was observed for both application types, however drift was associated only with the aerial application of these fungicides. Azoxystrobin and propiconazole persisted in the soil up to 301 d, with peak concentrations occurring approximately 30 d after application. The predominant mode of transport for these compounds was agricultural runoff water, with the majority of the fungicidal active ingredients leaving the target area during the first rain event following application. The timing of application in relation to the first rain event significantly affected the amount of loss that occurred, implying application practices should follow manufacturer recommended guidelines.

  19. Propiconazole-enhanced hepatic cell proliferation is associated with dysregulation of the cholesterol biosynthesis pathway leading to activation of Erk1/2 through Ras farnesylation.

    PubMed

    Murphy, Lynea A; Moore, Tanya; Nesnow, Stephen

    2012-04-15

    Propiconazole is a mouse hepatotumorigenic fungicide designed to inhibit CYP51, a key enzyme in the biosynthesis of ergosterol in fungi and is widely used in agriculture to prevent fungal growth. Metabolomic studies in mice revealed that propiconazole increased levels of hepatic cholesterol metabolites and bile acids, and transcriptomic studies revealed that genes within the cholesterol biosynthesis, cholesterol metabolism and bile acid biosyntheses pathways were up-regulated. Hepatic cell proliferation was also increased by propiconazole. AML12 immortalized hepatocytes were used to study propiconazole's effects on cell proliferation focusing on the dysregulation of cholesterol biosynthesis and resulting effects on Ras farnesylation and Erk1/2 activation as a primary pathway. Mevalonate, a key intermediate in the cholesterol biosynthesis pathway, increases cell proliferation in several cancer cell lines and tumors in vivo and serves as the precursor for isoprenoids (e.g. farnesyl pyrophosphate) which are crucial in the farnesylation of the Ras protein by farnesyl transferase. Farnesylation targets Ras to the cell membrane where it is involved in signal transduction, including the mitogen-activated protein kinase (MAPK) pathway. In our studies, mevalonic acid lactone (MVAL), a source of mevalonic acid, increased cell proliferation in AML12 cells which was reduced by farnesyl transferase inhibitors (L-744,832 or manumycin) or simvastatin, an HMG-CoA reductase inhibitor, indicating that this cell system responded to alterations in the cholesterol biosynthesis pathway. Cell proliferation in AML12 cells was increased by propiconazole which was reversed by co-incubation with L-744,832 or simvastatin. Increasing concentrations of exogenous cholesterol muted the proliferative effects of propiconazole and the inhibitory effects of L-733,832, results ascribed to reduced stimulation of the endogenous cholesterol biosynthesis pathway. Western blot analysis of subcellular

  20. Residues and dissipation kinetics of triazole fungicides difenoconazole and propiconazole in wheat and soil in Chinese fields.

    PubMed

    Zhang, Zhiyong; Jiang, Wayne; Jian, Qiu; Song, Wencheng; Zheng, Zuntao; Wang, Donglan; Liu, Xianjin

    2015-02-01

    An analytical method for simultaneously determining the residues of difenoconazole and propiconazole in wheat straw, wheat grain and soil was developed. Mean recoveries and relative standard deviations in all samples ranged 86.2-101.3% and 3.1-12.1% for propiconazole and difenoconazole. The half-lives of difenoconazole and propiconazole were 3.6-5.5days and 5.1-6.9days in wheat straws, and 4.9-5.8days and 6.1-8.4days in soil, respectively. The residues in wheat grain were found to be <0.01mg/kg, based on the application rate (135g a.i./ha) and the pre-harvest interval (PHI=28days) recommended by the manufacturer. The results suggest that the use of difenoconazole and propiconazole on wheat is considered to be safe under the Good Agricultural Practices (GAP) in the Chinese fields, and the main factors for pesticide residue in crops are application times, rates and pre-harvest intervals. PMID:25172726

  1. Residues and dissipation kinetics of triazole fungicides difenoconazole and propiconazole in wheat and soil in Chinese fields.

    PubMed

    Zhang, Zhiyong; Jiang, Wayne; Jian, Qiu; Song, Wencheng; Zheng, Zuntao; Wang, Donglan; Liu, Xianjin

    2015-02-01

    An analytical method for simultaneously determining the residues of difenoconazole and propiconazole in wheat straw, wheat grain and soil was developed. Mean recoveries and relative standard deviations in all samples ranged 86.2-101.3% and 3.1-12.1% for propiconazole and difenoconazole. The half-lives of difenoconazole and propiconazole were 3.6-5.5days and 5.1-6.9days in wheat straws, and 4.9-5.8days and 6.1-8.4days in soil, respectively. The residues in wheat grain were found to be <0.01mg/kg, based on the application rate (135g a.i./ha) and the pre-harvest interval (PHI=28days) recommended by the manufacturer. The results suggest that the use of difenoconazole and propiconazole on wheat is considered to be safe under the Good Agricultural Practices (GAP) in the Chinese fields, and the main factors for pesticide residue in crops are application times, rates and pre-harvest intervals.

  2. Variation in sorption of propiconazole with biochars: The effect of temperature, mineral, molecular structure, and nano-porosity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sorption behavior of propiconazole (PROPI) by plant-residue derived biochars (PLABs) and animal manure-derived biochars (ANIBs) obtained at three heating treatment temperatures (HTTs) at 300, 450 and 600 degrees Celsius (denoted as BCs300, BCs450, and BCs600) and their corresponding de-ashed BCs450 ...

  3. Propiconazole-enhanced hepatic cell proliferation is associated with dysregulation of the cholesterol biosynthesis pathway leading to activation of Erk1/2 through Ras farnesylation

    SciTech Connect

    Murphy, Lynea A.; Moore, Tanya; Nesnow, Stephen

    2012-04-15

    Propiconazole is a mouse hepatotumorigenic fungicide designed to inhibit CYP51, a key enzyme in the biosynthesis of ergosterol in fungi and is widely used in agriculture to prevent fungal growth. Metabolomic studies in mice revealed that propiconazole increased levels of hepatic cholesterol metabolites and bile acids, and transcriptomic studies revealed that genes within the cholesterol biosynthesis, cholesterol metabolism and bile acid biosyntheses pathways were up-regulated. Hepatic cell proliferation was also increased by propiconazole. AML12 immortalized hepatocytes were used to study propiconazole's effects on cell proliferation focusing on the dysregulation of cholesterol biosynthesis and resulting effects on Ras farnesylation and Erk1/2 activation as a primary pathway. Mevalonate, a key intermediate in the cholesterol biosynthesis pathway, increases cell proliferation in several cancer cell lines and tumors in vivo and serves as the precursor for isoprenoids (e.g. farnesyl pyrophosphate) which are crucial in the farnesylation of the Ras protein by farnesyl transferase. Farnesylation targets Ras to the cell membrane where it is involved in signal transduction, including the mitogen-activated protein kinase (MAPK) pathway. In our studies, mevalonic acid lactone (MVAL), a source of mevalonic acid, increased cell proliferation in AML12 cells which was reduced by farnesyl transferase inhibitors (L-744,832 or manumycin) or simvastatin, an HMG-CoA reductase inhibitor, indicating that this cell system responded to alterations in the cholesterol biosynthesis pathway. Cell proliferation in AML12 cells was increased by propiconazole which was reversed by co-incubation with L-744,832 or simvastatin. Increasing concentrations of exogenous cholesterol muted the proliferative effects of propiconazole and the inhibitory effects of L-733,832, results ascribed to reduced stimulation of the endogenous cholesterol biosynthesis pathway. Western blot analysis of subcellular

  4. Synthesis and in Vitro Antifungal Activities of Novel Benzamide Derivatives Containing a Triazole Moiety.

    PubMed

    Zhang, Wen; Sui, Guoqing; Li, Yulin; Fang, Mei; Yang, Xinjuan; Ma, Xihan; Zhou, Wenming

    2016-01-01

    The study reported the synthesis and antifungal activities in vitro against six phytopathogenic fungi of 17 novel N-[2-hydroxy-3,3-dimethyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butyl]benzamide derivatives. All the target compounds were synthesized and elucidated by means of MS, high resolution (HR)-MS, IR, (1)H- and (13)C-NMR analysis. The results showed that almost all the derivatives exhibited good activities against each of the tested fungi at the concentration of 50 µg/mL. Among them, 6h displayed excellent activity against Alternaria alternata with the median effective concentration value (EC50) of 1.77 µg/mL, superior to myclobutanil (EC50=6.23 µg/mL), a commercial fungicide with broad-spectrum bioactivities for plant protection and high-efficiency. Compound 6k showed the broadest antifungal spectrum, demonstrating positive activities against the corresponding fungi with EC50 values ranging from 0.98 to 6.71 µg/mL. Furthermore, 6e to 6i revealed good activities against Alternaria solani with EC50 values of 1.90, 4.51, 7.07, 2.00 and 5.44 µg/mL, respectively. The preliminary analysis of structure-activity relationship (SAR) demonstrated that the presence of F or Cl on the benzene ring remarkably improved the activity, while the introduction of 4-OMe or CF3 group decreased the activity in varying degrees. Thus, the present results strongly suggest that N-[2-hydroxy-3,3-dimethyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butyl]benzamide derivatives should be promising candidates for the development of novel antifungal agents in the effective control of phytopathogenic fungi. PMID:27250796

  5. Antifungal activity of diethyldithiocarbamate.

    PubMed

    Allerberger, F; Reisinger, E C; Söldner, B; Dierich, M P

    1989-10-01

    Sodium diethyldithiocarbamate (DTC) was evaluated for its ability to combat four different species of fungi in vitro. Using a microtiter-broth-dilution method we were able to demonstrate an antifungal activity against Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus and Mucor mucedo in doses achievable by intravenous administration in man.

  6. Antifungal susceptibility testing.

    PubMed Central

    Rex, J H; Pfaller, M A; Rinaldi, M G; Polak, A; Galgiani, J N

    1993-01-01

    Unlike antibacterial susceptibility testing, reliable antifungal susceptibility testing is still largely in its infancy. Many methods have been described, but they produce widely discrepant results unless such factors as pH, inoculum size, medium formulation, incubation time, and incubation temperature are carefully controlled. Even when laboratories agree upon a common method, interlaboratory agreement may be poor. As a result of numerous collaborative projects carried out both independently and under the aegis of the Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards, the effects of varying these factors have been extensively studied and a standard method which minimizes interlaboratory variability during the testing of Candida spp. and Cryptococcus neoformans has been proposed. This review summarizes this work, reviews the strengths and weaknesses of the proposed susceptibility testing standard, and identifies directions for future work. PMID:8269392

  7. Propiconazole Is a Specific and Accessible Brassinosteroid (BR) Biosynthesis Inhibitor for Arabidopsis and Maize

    PubMed Central

    Best, Norman B.; Budka, Joshua S.; Zhu, Jia-Ying; Choe, Sunghwa; Schulz, Burkhard

    2012-01-01

    Brassinosteroids (BRs) are steroidal hormones that play pivotal roles during plant development. In addition to the characterization of BR deficient mutants, specific BR biosynthesis inhibitors played an essential role in the elucidation of BR function in plants. However, high costs and limited availability of common BR biosynthetic inhibitors constrain their key advantage as a species-independent tool to investigate BR function. We studied propiconazole (Pcz) as an alternative to the BR inhibitor brassinazole (Brz). Arabidopsis seedlings treated with Pcz phenocopied BR biosynthetic mutants. The steady state mRNA levels of BR, but not gibberellic acid (GA), regulated genes increased proportional to the concentrations of Pcz. Moreover, root inhibition and Pcz-induced expression of BR biosynthetic genes were rescued by 24epi-brassinolide, but not by GA3 co-applications. Maize seedlings treated with Pcz showed impaired mesocotyl, coleoptile, and true leaf elongation. Interestingly, the genetic background strongly impacted the tissue specific sensitivity towards Pcz. Based on these findings we conclude that Pcz is a potent and specific inhibitor of BR biosynthesis and an alternative to Brz. The reduced cost and increased availability of Pcz, compared to Brz, opens new possibilities to study BR function in larger crop species. PMID:22590578

  8. Impact of Fungicides Chlorothalonil and Propiconazole on Microbial Activities in Groundnut (Arachis hypogaea L.) Soils

    PubMed Central

    Ramudu, A. C.; Mohiddin, G. Jaffer; Srinivasulu, M.; Madakka, M.; Rangaswamy, V.

    2011-01-01

    Introduction of agrochemicals (fungicides) into soil may have lasting effects on soil microbial activities and thus affect soil health. In order to determine the changes in microbial activity in a black clay and red sandy loam soils of groundnut (Arachis hypogaea L.) cultivated fields, a case study was conducted with propiconazole and chlorothalonil to evaluate its effects on soil enzymes (cellulase and invertase) throughout 40 days of incubation under laboratory conditions with different concentrations (1.0, 2.5, 5.0, 7.5, and 10.0 kg ha−1). Individual application of the two fungicides at 1.0, 2.5, and 5.0 kg ha−1 to the soil distinctly enhanced the activities of cellulase and invertase but at higher concentrations of 7.5 and 10 kg ha−1 was toxic or innocuous to both cellulase and invertase activities. In soil samples receiving 2.5–5.0 kg ha−1 of the fungicides, the accumulation of reducing sugar was pronounced more at 20 days, and the activity of the cellulase and invertase was drastically decreased with increasing period of incubation up to 30 and 40 days. PMID:23724306

  9. Molecular impact of propiconazole on Daphnia magna using a reproduction-related cDNA array.

    PubMed

    Soetaert, Anneleen; Moens, Lotte N; Van der Ven, Karlijn; Van Leemput, Koen; Naudts, Bart; Blust, Ronny; De Coen, Wim M

    2006-01-01

    We have developed a first version cDNA microarray of the cladoceran Daphnia magna. Through Suppression Subtractive Hybridisation PCR (SSH-PCR) 855 life stage-specific cDNAs were collected and used to document the toxicological mode of action of the pesticide propiconazole. DNA sequencing analysis revealed gene fragments related to important functional classes such as embryo development, energy metabolism, molting and cell cycle. Major changes in transcription were observed in organisms exposed for 4 and 8 days to 1 microg/mL. After 4 days a 3-fold down-regulation of the gene encoding the yolk protein, vitellogenin, was observed indicating impaired oocyte maturation. Moreover, genes such as a larval-specific gene and chaperonin were repressed, whereas the heat shock 90 protein and ATP synthase were induced. Organismal effects clearly confirmed the major molecular findings: at the highest concentration (1 microg/mL) adult growth was significantly (p < 0.05) impaired and increased developmental effects in the offspring could be noted. We have demonstrated the potential of microarray analysis in toxicity screening with D. magna. The use of vitellogenin mRNA as a rapid biomarker of reproductive effects in chronic toxicity studies with cladocerans is suggested. PMID:16311075

  10. Changes in antioxidant metabolism of Vigna unguiculata (L.) Walp. by propiconazole under water deficit stress.

    PubMed

    Manivannan, P; Abdul Jaleel, C; Kishorekumar, A; Sankar, B; Somasundaram, R; Sridharan, R; Panneerselvam, R

    2007-05-15

    In the present study, a pot culture experiment was conducted to estimate the ameliorating effect of propiconazole (PCZ) on drought stress in cowpea (Vigna unguiculata (L.) Walp.) plants. From 30 days after sowing (DAS), the plants were subjected to 3, 6 and 9 days interval drought (DID) stress and drought stress with PCZ at 15 and 15 mg l(-1) PCZ alone and 1 day interval irrigation was kept as control. The plant samples were collected on 34 DAS (3 DID), 37 DAS (6 DID) and 40 DAS (9 DID). The plants were separated into root, stem and leaf for estimating the antioxidant contents and activities of antioxidant enzymes. Individual and combined drought stress and PCZ treatments increased ascorbic acid (AA), alpha-tocopherol (alpha-toc) contents, superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and polyphenol oxidase (PPO) activities when compared to control. The PCZ treatment mitigated the adverse effects of drought stress by increasing the antioxidant potentials and thereby paved the way for overcoming drought stress in V. unguiculata plants.

  11. Propiconazole is a specific and accessible brassinosteroid (BR) biosynthesis inhibitor for Arabidopsis and maize.

    PubMed

    Hartwig, Thomas; Corvalan, Claudia; Best, Norman B; Budka, Joshua S; Zhu, Jia-Ying; Choe, Sunghwa; Schulz, Burkhard

    2012-01-01

    Brassinosteroids (BRs) are steroidal hormones that play pivotal roles during plant development. In addition to the characterization of BR deficient mutants, specific BR biosynthesis inhibitors played an essential role in the elucidation of BR function in plants. However, high costs and limited availability of common BR biosynthetic inhibitors constrain their key advantage as a species-independent tool to investigate BR function. We studied propiconazole (Pcz) as an alternative to the BR inhibitor brassinazole (Brz). Arabidopsis seedlings treated with Pcz phenocopied BR biosynthetic mutants. The steady state mRNA levels of BR, but not gibberellic acid (GA), regulated genes increased proportional to the concentrations of Pcz. Moreover, root inhibition and Pcz-induced expression of BR biosynthetic genes were rescued by 24epi-brassinolide, but not by GA(3) co-applications. Maize seedlings treated with Pcz showed impaired mesocotyl, coleoptile, and true leaf elongation. Interestingly, the genetic background strongly impacted the tissue specific sensitivity towards Pcz. Based on these findings we conclude that Pcz is a potent and specific inhibitor of BR biosynthesis and an alternative to Brz. The reduced cost and increased availability of Pcz, compared to Brz, opens new possibilities to study BR function in larger crop species.

  12. Impact of Fungicides Chlorothalonil and Propiconazole on Microbial Activities in Groundnut (Arachis hypogaea L.) Soils.

    PubMed

    Ramudu, A C; Mohiddin, G Jaffer; Srinivasulu, M; Madakka, M; Rangaswamy, V

    2011-01-01

    Introduction of agrochemicals (fungicides) into soil may have lasting effects on soil microbial activities and thus affect soil health. In order to determine the changes in microbial activity in a black clay and red sandy loam soils of groundnut (Arachis hypogaea L.) cultivated fields, a case study was conducted with propiconazole and chlorothalonil to evaluate its effects on soil enzymes (cellulase and invertase) throughout 40 days of incubation under laboratory conditions with different concentrations (1.0, 2.5, 5.0, 7.5, and 10.0 kg ha(-1)). Individual application of the two fungicides at 1.0, 2.5, and 5.0 kg ha(-1) to the soil distinctly enhanced the activities of cellulase and invertase but at higher concentrations of 7.5 and 10 kg ha(-1) was toxic or innocuous to both cellulase and invertase activities. In soil samples receiving 2.5-5.0 kg ha(-1) of the fungicides, the accumulation of reducing sugar was pronounced more at 20 days, and the activity of the cellulase and invertase was drastically decreased with increasing period of incubation up to 30 and 40 days.

  13. Molecular impact of propiconazole on Daphnia magna using a reproduction-related cDNA array.

    PubMed

    Soetaert, Anneleen; Moens, Lotte N; Van der Ven, Karlijn; Van Leemput, Koen; Naudts, Bart; Blust, Ronny; De Coen, Wim M

    2006-01-01

    We have developed a first version cDNA microarray of the cladoceran Daphnia magna. Through Suppression Subtractive Hybridisation PCR (SSH-PCR) 855 life stage-specific cDNAs were collected and used to document the toxicological mode of action of the pesticide propiconazole. DNA sequencing analysis revealed gene fragments related to important functional classes such as embryo development, energy metabolism, molting and cell cycle. Major changes in transcription were observed in organisms exposed for 4 and 8 days to 1 microg/mL. After 4 days a 3-fold down-regulation of the gene encoding the yolk protein, vitellogenin, was observed indicating impaired oocyte maturation. Moreover, genes such as a larval-specific gene and chaperonin were repressed, whereas the heat shock 90 protein and ATP synthase were induced. Organismal effects clearly confirmed the major molecular findings: at the highest concentration (1 microg/mL) adult growth was significantly (p < 0.05) impaired and increased developmental effects in the offspring could be noted. We have demonstrated the potential of microarray analysis in toxicity screening with D. magna. The use of vitellogenin mRNA as a rapid biomarker of reproductive effects in chronic toxicity studies with cladocerans is suggested.

  14. Multiple biomarkers responses in juvenile rainbow trout, Oncorhynchus mykiss, after acute exposure to a fungicide propiconazole.

    PubMed

    Li, Zhi-Hua; Zlabek, Vladimir; Velisek, Josef; Grabic, Roman; Machova, Jana; Kolarova, Jitka; Li, Ping; Randak, Tomas

    2013-03-01

    In this study, the toxic effects of propiconazole (PCZ), a triazole fungicide present in aquatic environment, were studied in juvenile rainbow trout, Oncorhynchus mykiss, by acute toxicity test with the concentration of 5.04 mg/L (96 h LC50). Morphological indices, hematological parameters, liver xenobiotic-metabolizing response, and tissue antioxidant status were evaluated. Compared with the control group, fish exposed to PCZ showed significantly higher Leuko, PCV, MCHC, and hepatic EROD, and significantly lower MCV. CF and HSI were not significantly different among groups. SOD, CAT, GPx, and GR activities increased significantly in liver of experimental groups, but decreased significantly in gill. In general, antioxidant enzyme activity in intestine was less evident than in liver. Oxidative stress indices (levels of LPO and CP) were significantly higher in gill. Additionally, through chemometrics of all parameters measured in this study, two groups with 67.29% of total accumulated variance were distinguished. In short, the physiological and biochemical responses in different tissues of fish indicated that PCZ-induced the stressful environmental conditions. But according to PCZ residual status in the natural environment, more long-term experiments at lower concentrations will be necessary in the future. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.

  15. The hepatocarcinogenic conazoles: cyproconazole, epoxiconazole, and propiconazole induce a common set of toxicological and transcriptional responses.

    PubMed

    Hester, Susan; Moore, Tanya; Padgett, William T; Murphy, Lynea; Wood, Charles E; Nesnow, Stephen

    2012-05-01

    Conazoles are fungicides used as agricultural pesticides and pharmaceutical products. We investigated whether a common core of toxicological and transcriptional responses underlies the observed carcinogenic effects of three conazoles: cyproconazole, epoxiconazole, and propiconazole. In studies where mice were fed diets of these conazoles for 30 days, we found a common set of toxicological effects altered by these conazoles: hepatomegaly, hepatocellular hypertrophy, decreased serum cholesterol, decreased hepatic levels of all-trans-retinoic acid, and increased hepatic cell proliferation. Microarray-based transcriptional analysis revealed 330 significantly altered probe sets common to these conazoles, many of which showed strong dose responses for cytochrome P450, glutathione S-transferase, and oxidative stress genes. More detailed analyses identified a subset of 80 altered genes common to the three conazoles that were associated with cancer. Pathways associated with these genes included xenobiotic metabolism, oxidative stress, cell signaling, and cell proliferation. A common TGFα-centric pathway was identified within the 80-gene set, which, in combination with the toxicological and other transcriptomic findings, provides a more refined toxicity profile for these carcinogenic conazoles.

  16. Study on the binding of propiconazole to protein by molecular modeling and a multispectroscopic method.

    PubMed

    Wang, Chao; Li, Ying

    2011-08-10

    Propiconazole (PCZ) is an N-substituted triazole used as a fungicide on fruits, grains, seeds, hardwoods, and conifers. Although the triazole fungicides have shorter half-lives and lower bioaccumulation than the organochlorine pesticides, possible detrimental effects on the aquatic ecosystem and human health also exist. To evaluate the toxicity of PCZ at the protein level, its effects on human serum albumin (HSA) were characterized by molecular modeling and multispectroscopic method. On the basis of the fluorescence spectra, PCZ exhibited remarkable fluorescence quenching, which was attributed to the formation of a complex. The thermodynamic parameters ΔH and ΔS were calculated to be -14.980 KJ/mol and 26.966 J/(mol K), respectively, according to the van't Hoff equation, which suggests hydrophobic and electrostatic interactions are the predominant intermolecular forces in stabilizing the PCZ-protein complex. Furthermore, HSA conformation was slightly altered in the presence of PCZ. These results indicated that PCZ indeed affected the conformation of HSA.

  17. PROPICONAZOLE-INDUCED CYTOCHROME P450 GENE EXPRESSION AND ENZYMATIC ACTIVITIES IN RAT AND MOUSE LIVER

    EPA Science Inventory

    Conazoles are N-substituted azole antifungal agents used as both pesticides and drugs. Some of these compounds are hepatocarcinogenic in mice and some can induce thyroid tumors in rats. Many of these compounds are able to induce and/or inhibit mammalian hepatic cytochrome P450s t...

  18. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    PubMed Central

    Gupta, Deepa; Jain, D. K.

    2015-01-01

    Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen–Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent. PMID:26317075

  19. Variation in sorption of propiconazole with biochars: The effect of temperature, mineral, molecular structure, and nano-porosity.

    PubMed

    Sun, Ke; Kang, Mingjie; Ro, Kyoung S; Libra, Judy A; Zhao, Ye; Xing, Baoshan

    2016-01-01

    Sorption behavior of propiconazole (PROPI) by plant-residue derived biochars (PLABs) and animal waste-derived biochars (ANIBs) obtained at three heating treatment temperatures (HTTs) (300, 450 and 600 °C) (e.g., BCs300, BCs450, and BCs600) and their corresponding de-ashed BCs450 was investigated. PLABs belonged to high- or medium-C biochars and ANIBs were low-C biochars. Surface C concentrations of the tested biochars were generally higher than their corresponding bulk C. Surface polar groups were mainly composed of O-containing groups of minerals within biochars. The nonlinearity coefficients (n) of propiconazole (PROPI) sorption isotherms ranged from 0.23 to 0.64, which was significantly and negatively related to organic carbon (OC)-normalized CO2-surface area (CO2-SA/OC) of biochars. This correlation along with the positive relationship between CO2-SA/OC and aromaticity indicates that pore-filling in nanopores within aromatic C dominate nonlinear PROPI sorption. HTTs or C contents do not necessarily regulate PROPI sorption. Removal of minerals from BCs450 elevated PROPI sorption because minerals may exert certain influence on sorption via impacting spatial arrangement of polar groups and/or organic matter (OM)-mineral interactions. This study helps to better understand sorption behavior of PROPI to biochars and evaluate the potential role of biochar in water treatment systems. PMID:26206746

  20. Variation in sorption of propiconazole with biochars: The effect of temperature, mineral, molecular structure, and nano-porosity.

    PubMed

    Sun, Ke; Kang, Mingjie; Ro, Kyoung S; Libra, Judy A; Zhao, Ye; Xing, Baoshan

    2016-01-01

    Sorption behavior of propiconazole (PROPI) by plant-residue derived biochars (PLABs) and animal waste-derived biochars (ANIBs) obtained at three heating treatment temperatures (HTTs) (300, 450 and 600 °C) (e.g., BCs300, BCs450, and BCs600) and their corresponding de-ashed BCs450 was investigated. PLABs belonged to high- or medium-C biochars and ANIBs were low-C biochars. Surface C concentrations of the tested biochars were generally higher than their corresponding bulk C. Surface polar groups were mainly composed of O-containing groups of minerals within biochars. The nonlinearity coefficients (n) of propiconazole (PROPI) sorption isotherms ranged from 0.23 to 0.64, which was significantly and negatively related to organic carbon (OC)-normalized CO2-surface area (CO2-SA/OC) of biochars. This correlation along with the positive relationship between CO2-SA/OC and aromaticity indicates that pore-filling in nanopores within aromatic C dominate nonlinear PROPI sorption. HTTs or C contents do not necessarily regulate PROPI sorption. Removal of minerals from BCs450 elevated PROPI sorption because minerals may exert certain influence on sorption via impacting spatial arrangement of polar groups and/or organic matter (OM)-mineral interactions. This study helps to better understand sorption behavior of PROPI to biochars and evaluate the potential role of biochar in water treatment systems.

  1. Letter to the Editor, Response to Commentary "Re-Evaluation of the Big Blue® Mouse Assay of Propiconazole Suggests Lack of Mutagenicity"

    EPA Science Inventory

    In their commentary titled "Re-Evaluation of the Big Blue® Mouse Assay of Propiconazole Suggests Lack of Mutagenicity", Shane et 01. present an overview of portions of our previously reported work examining the potential for some conazole fungicides to induce increases in mutant ...

  2. Loss of propiconazole and its four stereoisomers from the water phase of two soil-water slurries as measured by capillary electrophoresis.

    PubMed

    Garrison, Arthur W; Avants, Jimmy K; Miller, Rebecca D

    2011-08-01

    Propiconazole is a chiral fungicide used in agriculture for control of many fungal diseases on a variety of crops. This use provides opportunities for pollution of soil and, subsequently, groundwater. The rate of loss of propiconazole from the water phase of two different soil-water slurries spiked with the fungicide at 50 mg/L was followed under aerobic conditions over five months; the t(1/2) was 45 and 51 days for the two soil slurries. To accurately assess environmental and human risk, it is necessary to analyze the separate stereoisomers of chiral pollutants, because it is known that for most such pollutants, both biotransformation and toxicity are likely to be stereoselective. Micellar electrokinetic chromatography (MEKC), the mode of capillary electrophoresis used for analysis of neutral chemicals, was used for analysis of the four propiconazole stereoisomers with time in the water phase of the slurries. MEKC resulted in baseline separation of all stereoisomers, while GC-MS using a chiral column gave only partial separation. The four stereoisomers of propiconazole were lost from the aqueous phase of the slurries at experimentally equivalent rates, i.e., there was very little, if any, stereoselectivity. No loss of propiconazole was observed from the autoclaved controls of either soil, indicating that the loss from active samples was most likely caused by aerobic biotansformation, with a possible contribution by sorption to the non-autoclaved active soils. MEKC is a powerful tool for separation of stereoisomers and can be used to study the fate and transformation kinetics of chiral pesticides in water and soil.

  3. DIFFERENTIAL EXPRESSION OF RETINOIC ACID BIOSYNTHETIC AND METABOLISM GENES IN LIVERS FROM MICE TREATED WITH HEPATOTUMORIGENIC AND NON-HEPATOTUMORIGENIC CONAZOLES

    EPA Science Inventory

    Conazoles are fungicides used in crop protection and as pharmaceuticals. Triadimefon and propiconazole are hepatotumorigenic in mice, while myclobutanil is not. Previous toxicogenomic studies suggest that alteration of the retinoic acid metabolism pathway may play a key event in ...

  4. RAMAN SPECTROSCOPY-BASED METABOLOMICS FOR DIFFERENTIATING EXPOSURES TO TRIAZOLE FUNGICIDES USING RAT URINE

    EPA Science Inventory

    Normal Raman spectroscopy was evaluated as a metabolomic tool for assessing the impacts of exposure to environmental contaminants, using rat urine collected during the course of a toxicological study. Specifically, one of three triazole fungicides, myclobutanil, propiconazole or ...

  5. GENE EXPRESSION PROFILING IN LIVER AND TESTIS OF RATS TO CHARACTERIZE THE TOXICITY OF TRIAZOLE FUNGICIDES.

    EPA Science Inventory

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected ...

  6. Gene Expression Profiling in Liver and Testis of Rats to Characterize the Toxicity of Triazole Fungicides

    EPA Science Inventory

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected ...

  7. CHARACTERIZATION OF CYPS IN THE METABOLISM OF ALL TRANS RETINOIC ACID BY LIVER MICROSOMES FROM MICE TREATED WITH CONAZOLES

    EPA Science Inventory

    Conazoles are fungicides used in crop protection and as pharmaceuticals. Triadimefon and propiconazole are hepatotumorigenic in mice, while myclobutanil is not. Previous toxicogenomic studies suggest that alteration of the retinoic acid metabolism pathway may involve in conazole-...

  8. ALTERATIONS IN A11 TRANS RETINOIC ACID METABOLISM IN LIVER MICROSOMES FROM MICE TREATED WITH HEPATOTUMORIGENIC AND NON-HEPATOTUMORIGENIC CONAZOLES

    EPA Science Inventory

    Conazoles are fungicides used in crop protection and as pharmaceuticals. Triadimefon and propiconazole are hepatotumorigenic in mice, while myclobutanil is not. Previous toxicogenomic studies suggest that alteration of the retinoic acid metabolism pathway may be a key event in co...

  9. COMPARISON OF GENE EXPRESSION PROFILES FROM RATS FED THREE TOXICOLOGICALLY DIFFERENT CONAZOLES

    EPA Science Inventory

    Conazoles arc a class of fungicides used as pharmaceutical and agricultural products. In chronic bioassays, triadimefon was hepatotoxic and induced transitional cell adenomas in the thyroid gland. Both propiconazole and myclobutanil were hepatotoxic but had no effect on the thyro...

  10. Quantitative changes in endogenous DNA damage correlate with conazole mutagenicity and tumorigenicity.

    EPA Science Inventory

    The mouse liver tumorigenic conazolefungicides triadimefon and propiconazole have previously been shown to be in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses, whereas the nontumorigenic conazole myclobutanil w...

  11. Comparison of echinocandin antifungals

    PubMed Central

    Eschenauer, Gregory; DePestel, Daryl D; Carver, Peggy L

    2007-01-01

    The incidence of invasive fungal infections, especially those due to Aspergillus spp. and Candida spp., continues to increase. Despite advances in medical practice, the associated mortality from these infections continues to be substantial. The echinocandin antifungals provide clinicians with another treatment option for serious fungal infections. These agents possess a completely novel mechanism of action, are relatively well-tolerated, and have a low potential for serious drug–drug interactions. At the present time, the echinocandins are an option for the treatment of infections due Candida spp (such as esophageal candidiasis, invasive candidiasis, and candidemia). In addition, caspofungin is a viable option for the treatment of refractory aspergillosis. Although micafungin is not Food and Drug Administration-approved for this indication, recent data suggests that it may also be effective. Finally, caspofungin- or micafungin-containing combination therapy should be a consideration for the treatment of severe infections due to Aspergillus spp. Although the echinocandins share many common properties, data regarding their differences are emerging at a rapid pace. Anidulafungin exhibits a unique pharmacokinetic profile, and limited cases have shown a potential far activity in isolates with increased minimum inhibitory concentrations to caspofungin and micafungin. Caspofungin appears to have a slightly higher incidence of side effects and potential for drug–drug interactions. This, combined with some evidence of decreasing susceptibility among some strains of Candida, may lessen its future utility. However, one must take these findings in the context of substantially more data and use with caspofungin compared with the other agents. Micafungin appears to be very similar to caspofungin, with very few obvious differences between the two agents. PMID:18360617

  12. Antifungal Prophylaxis in Immunocompromised Patients.

    PubMed

    Vazquez, Lourdes

    2016-01-01

    Invasive fungal infections (IFIs) represent significant complications in patients with hematological malignancies. Chemoprevention of IFIs may be important in this setting, but most antifungal drugs have demonstrated poor efficacy, particularly in the prevention of invasive aspergillosis. Antifungal prophylaxis in hematological patients is currently regarded as the gold standard in situations with a high risk of infection, such as acute leukemia, myelodysplastic syndromes, and autologous or allogeneic hematopoietic stem cell transplantation. Over the years, various scientific societies have established a series of recommendations for antifungal prophylaxis based on prospective studies performed with different drugs. However, the prescription of each agent must be personalized, adapting its administration to the characteristics of individual patients and taking into account possible interactions with concomitant medication. PMID:27648203

  13. Haloprogin: a Topical Antifungal Agent

    PubMed Central

    Harrison, E. F.; Zwadyk, P.; Bequette, R. J.; Hamlow, E. E.; Tavormina, P. A.; Zygmunt, W. A.

    1970-01-01

    Haloprogin was shown to be a highly effective agent for the treatment of experimentally induced topical mycotic infections in guinea pigs. Its in vitro spectrum of activity also includes yeasts, yeastlike fungi (Candida species), and certain gram-positive bacteria. The in vitro and in vivo antifungal activity of haloprogin against dermatophytes was equal to that observed with tolnaftate. The striking differences between the two agents were the marked antimonilial and selective antibacterial activities shown by haloprogin, contrasted with the negligible activities found with tolnaftate. Addition of serum decreased the in vitro antifungal activity of haloprogin to a greater extent than that of tolnaftate; however, diminished antifungal activity was not observed when haloprogin was applied topically to experimental dermatophytic infections. Based on its broad spectrum of antimicrobial activity, haloprogin may prove to be a superior topical agent in the treatment of dermatophytic and monilial infections in man. PMID:5422306

  14. Antifungal Prophylaxis in Immunocompromised Patients

    PubMed Central

    Vazquez, Lourdes

    2016-01-01

    Invasive fungal infections (IFIs) represent significant complications in patients with hematological malignancies. Chemoprevention of IFIs may be important in this setting, but most antifungal drugs have demonstrated poor efficacy, particularly in the prevention of invasive aspergillosis. Antifungal prophylaxis in hematological patients is currently regarded as the gold standard in situations with a high risk of infection, such as acute leukemia, myelodysplastic syndromes, and autologous or allogeneic hematopoietic stem cell transplantation. Over the years, various scientific societies have established a series of recommendations for antifungal prophylaxis based on prospective studies performed with different drugs. However, the prescription of each agent must be personalized, adapting its administration to the characteristics of individual patients and taking into account possible interactions with concomitant medication.

  15. Antifungal Prophylaxis in Immunocompromised Patients

    PubMed Central

    Vazquez, Lourdes

    2016-01-01

    Invasive fungal infections (IFIs) represent significant complications in patients with hematological malignancies. Chemoprevention of IFIs may be important in this setting, but most antifungal drugs have demonstrated poor efficacy, particularly in the prevention of invasive aspergillosis. Antifungal prophylaxis in hematological patients is currently regarded as the gold standard in situations with a high risk of infection, such as acute leukemia, myelodysplastic syndromes, and autologous or allogeneic hematopoietic stem cell transplantation. Over the years, various scientific societies have established a series of recommendations for antifungal prophylaxis based on prospective studies performed with different drugs. However, the prescription of each agent must be personalized, adapting its administration to the characteristics of individual patients and taking into account possible interactions with concomitant medication. PMID:27648203

  16. Treating chromoblastomycosis with systemic antifungals.

    PubMed

    Bonifaz, Alexandro; Paredes-Solís, Vanessa; Saúl, Amado

    2004-02-01

    Chromoblastomycosis is a subcutaneous mycosis for which there is no treatment of choice but rather, several treatment options, with low cure rates and many relapses. The choice of treatment should consider several conditions, such as the causal agent (the most common one being Fonsecaea pedrosoi ), extension of the lesions, clinical topography and health status of the patient. Most oral and systemic antifungals have been used; the best results have been obtained with itraconazole and terbinafine at high doses, for a mean of 6 - 12 months. In extensive and refractory cases, chemotherapy with oral antifungals may be associated with thermotherapy (local heat and/or cryosurgery). Limited or early cases may be managed with surgical methods, always associated with oral antifungal agents. It is important to determine the in vitro sensitivity of the major causal agents to the various drugs, by estimating the minimum inhibitory concentration, as well as drug tolerability and drug interactions.

  17. Simple and rapid method for simultaneous gas chromatographic determination of bitertanol, metalaxyl, oxadixyl, propiconazole, and triadimefon residues in cucumbers.

    PubMed

    Lee, W O; Wong, S K

    1995-10-01

    A simple and rapid method for the determination of bitertanol, metalaxyl, oxadixyl, propiconazole and triadimefon residues in cucumbers has been developed. The fungicide residues were extracted from the sample with ethyl acetate and determined, after an automated gel permeation chromatographic clean-up, by GC with nitrogen-phosphorus detection. Cucumbers fortified with fungicides in the laboratory were analysed using the proposed method and that of Luke, Frooberg, Masumoto and Doose (J. Assoc. Off. Anal. Chem., 1981, 64, 1187). For the proposed method, mean recoveries ranged from 87.9% for bitertanol to 96.5% for oxadixyl. For the method of Luke et al. mean recoveries ranged from 79.8% for triadimefon to 97.8% for bitertanol. Cucumbers treated with the fungicides in the field were also analysed by these two methods. For the determination of all these five fungicides, no difference was observed at the 5% significance level.

  18. Use of antifungal drugs in hematology

    PubMed Central

    Nucci, Marcio

    2012-01-01

    Invasive fungal disease represents a major complication in hematological patients. Antifungal agents are frequently used in hematologic patients for different purposes. In neutropenic patients, antifungal agents may be used as prophylaxis, as empiric or preemptive therapy, or to treat an invasive fungal disease that has been diagnosed. The hematologist must be familiar with the epidemiology, diagnostic tools and strategies of antifungal use, as well as the pharmacologic proprieties of the different antifungal agents. In this paper the principal antifungal agents used in hematologic patients will be discussed as will the clinical scenarios where these agents have been used. PMID:23125547

  19. Antifungal resistance in yeast vaginitis.

    PubMed Central

    Dun, E.

    1999-01-01

    The increased number of vaginal yeast infections in the past few years has been a disturbing trend, and the scientific community has been searching for its etiology. Several theories have been put forth to explain the apparent increase. First, the recent widespread availability of low-dosage, azole-based over-the-counter antifungal medications for vaginal yeast infections encourages women to self-diagnose and treat, and women may be misdiagnosing themselves. Their vaginitis may be caused by bacteria, parasites or may be a symptom of another underlying health condition. As a result, they may be unnecessarily and chronically expose themselves to antifungal medications and encourage fungal resistance. Second, medical technology has increased the life span of seriously immune compromised individuals, yet these individuals are frequently plagued by opportunistic fungal infections. Long-term and intense azole-based antifungal treatment has been linked to an increase in resistant Candida and non-Candida species. Thus, the future of limiting antifungal resistance lies in identifying the factors promoting resistance and implementing policies to prevent it. PMID:10907778

  20. Antifungal activity of juniper extracts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sawdust from three species of Juniperus (i.e., J. virginianna, J. occidentalis, and J. ashei) were extracted with hexane or ethanol and the extracts tested for antifungal activity against four species of wood-rot fungi. These species studied represent the junipers with the greatest potential for co...

  1. A Prototype Antifungal Contact Lens

    PubMed Central

    Ciolino, Joseph B.; Hudson, Sarah P.; Mobbs, Ashley N.; Hoare, Todd R.; Iwata, Naomi G.; Fink, Gerald R.

    2011-01-01

    Purpose. To design a contact lens to treat and prevent fungal ocular infections. Methods. Curved contact lenses were created by encapsulating econazole-impregnated poly(lactic-co-glycolic) acid (PLGA) films in poly(hydroxyethyl methacrylate) (pHEMA) by ultraviolet photopolymerization. Release studies were conducted in phosphate-buffered saline at 37°C with continuous shaking. The contact lenses and their release media were tested in an antifungal assay against Candida albicans. Cross sections of the pre- and postrelease contact lenses were characterized by scanning electron microscopy and by Raman spectroscopy. Results. Econazole-eluting contact lenses provided extended antifungal activity against Candida albicans fungi. Fungicidal activity varied in duration and effectiveness depending on the mass of the econazole-PLGA film encapsulated in the contact lens. Conclusions. An econazole-eluting contact lens could be used as a treatment for fungal ocular infections. PMID:21527380

  2. Defensins: antifungal lessons from eukaryotes

    PubMed Central

    Silva, Patrícia M.; Gonçalves, Sónia; Santos, Nuno C.

    2014-01-01

    Over the last years, antimicrobial peptides (AMPs) have been the focus of intense research toward the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantae, and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components) are presented. Additionally, recent works on antifungal defensins structure, activity, and cytotoxicity are also reviewed. PMID:24688483

  3. Antibacterial and Antifungal Compounds from Marine Fungi

    PubMed Central

    Xu, Lijian; Meng, Wei; Cao, Cong; Wang, Jian; Shan, Wenjun; Wang, Qinggui

    2015-01-01

    This paper reviews 116 new compounds with antifungal or antibacterial activities as well as 169 other known antimicrobial compounds, with a specific focus on January 2010 through March 2015. Furthermore, the phylogeny of the fungi producing these antibacterial or antifungal compounds was analyzed. The new methods used to isolate marine fungi that possess antibacterial or antifungal activities as well as the relationship between structure and activity are shown in this review. PMID:26042616

  4. Topical antifungals for seborrhoeic dermatitis

    PubMed Central

    Okokon, Enembe O; Verbeek, Jos H; Ruotsalainen, Jani H; Ojo, Olumuyiwa A; Bakhoya, Victor Nyange

    2015-01-01

    Background Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy. Objectives To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults. A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS. Search methods We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials. Selection criteria Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life. Data collection and analysis Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high. Main results We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies. Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141

  5. Use of hematological and plasma biochemical parameters to assess the chronic effects of a fungicide propiconazole on a freshwater teleost.

    PubMed

    Li, Zhi-Hua; Velisek, Josef; Grabic, Roman; Li, Ping; Kolarova, Jitka; Randak, Tomas

    2011-04-01

    Blood is an indicator of physiological condition of an animal. Therefore, the chronic effects of propiconazole, a triazole fungicide present in aquatic environment, on hematology of rainbow trout were investigated in this study. Fish were exposed at various concentrations of PCZ (0.2, 50 and 500 μg L(-1)) for 7, 20 and 30 d. Multiple biomarkers were measured, including hematological indices (hemoglobin concentration, red blood cells count, hematocrit, leukocyte count, mean erythrocyte hemoglobin, mean erythrocyte volume and mean color concentration) and plasma biochemical parameters (ammonia, glucose, total proteins, creatine kinase, lactate dehydrogenase, alanine aminotransferase and aspartate aminotransferase). Through principal component analysis and integrated biomarker response assessment, influence extent induced by PCZ-stress of each test group was distinguished. Additional, all parameters measured in this study displayed different dependent patterns to PCZ concentrations and exposure time by two-way ANOVA. The results of this study indicate that chronic exposure of PCZ has altered multiple physiological indices in fish hematology and CK activity may be an early biomarker of PCZ toxicity; however, before these parameters are used as special biomarkers for monitoring residual PCZ in aquatic environment, more detailed experiments in laboratory need to be performed in the future.

  6. Differential sensitivity of barley (Hordeum vulgare L.) to chlorpyrifos and propiconazole: Morphology, cytogenetic assay and photosynthetic pigments.

    PubMed

    Dubey, Pragyan; Mishra, Amit Kumar; Shukla, Pratiksha; Singh, Ashok Kumar

    2015-10-01

    The present investigation was performed to evaluate the effects of an insecticide and fungicide, namely, chlorpyrifos (CP) and propiconazole (PZ) on barley (Hordeum vulgare L. variety Karan-16). The seeds were treated with three concentrations of CP and PZ, i.e., 0.05%, 0.1% and 0.5% for 6 hours after different pre-soaking durations of 7, 17 and 27 hours. Different pre-soaking durations (7, 17 and 27 h) represent three phases of the cell cycle i.e., G1, S and G2, respectively. Double distilled water and ethyl methane sulfonate were used as negative and positive controls, respectively. As compared to their respective controls, treated root tip meristematic cells of barley showed significant reductions in the germination percentage, seedling height, mitotic index and comparative increase in chromosomal aberrations against both the pesticides, and the magnitude was higher in CP. After treatment with the pesticides, chlorophyll and carotenoid contents increased up to 0.1% but reduced at 0.5% and the decrease was more prominent in CP as compared to PZ. In treated cells, fragmentation, stickiness, bridges, multipolar anaphase and diagonal anaphase were observed as aberrations. As compared to control, chromosomal aberrations were higher in CP as compared to PZ. The results of the present study concluded that CP induced chromosomal aberrations were more frequent than PZ; hence it has higher probability to cause genotoxicity in barley.

  7. Re-evaluation of the Big Blue® mouse assay of propiconazole suggests lack of mutagenicity.

    PubMed

    Shane, Barbara S; Zeiger, Errol; Piegorsch, Walter W; Booth, Ewan D; Goodman, Jay I; Peffer, Richard C

    2012-01-01

    Propiconazole (PPZ) is a conazole fungicide that is not mutagenic, clastogenic, or DNA damaging in standard in vitro and in vivo genetic toxicity tests for gene mutations, chromosome aberrations, DNA damage, and cell transformation. However, it was demonstrated to be a male mouse liver carcinogen when administered in food for 24 months only at a concentration of 2,500 ppm that exceeded the maximum tolerated dose based on increased mortality, decreased body weight gain, and the presence of liver necrosis. PPZ was subsequently tested for mutagenicity in the Big Blue® transgenic mouse assay at the 2,500 ppm dose, and the result was reported as positive by Ross et al. ([2009]: Mutagenesis 24:149-152). Subsets of the mutants from the control and PPZ-exposed groups were sequenced to determine the mutation spectra and a multivariate clustering analysis method purportedly substantiated the increase in mutant frequency with PPZ (Ross and Leavitt. [2010]: Mutagenesis 25:231-234). However, as reported here, the results of the analysis of the mutation spectra using a conventional method indicated no treatment-related differences in the spectra. In this article, we re-examine the Big Blue® mouse findings with PPZ and conclude that the compound does not act as a mutagen in vivo.

  8. Antifungal Activity of C-27 Steroidal Saponins

    PubMed Central

    Yang, Chong-Ren; Zhang, Ying; Jacob, Melissa R.; Khan, Shabana I.; Zhang, Ying-Jun; Li, Xing-Cong

    2006-01-01

    As part of our search for new antifungal agents from natural resources, 22 C-27 steroidal saponins and 6 steroidal sapogenins isolated from several monocotyledonous plants were tested for their antifungal activity against the opportunistic pathogens Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and Aspergillus fumigatus. The results showed that the antifungal activity of the steroidal saponins was associated with their aglycone moieties and the number and structure of monosaccharide units in their sugar chains. Within the 10 active saponins, four tigogenin saponins (compounds 1 to 4) with a sugar moiety of four or five monosaccharide units exhibited significant activity against C. neoformans and A. fumigatus, comparable to the positive control amphotericin B. The antifungal potency of these compounds was not associated with cytotoxicity to mammalian cells. This suggests that the C-27 steroidal saponins may be considered potential antifungal leads for further preclinical study. PMID:16641439

  9. Natural and synthetic peptides with antifungal activity.

    PubMed

    Ciociola, Tecla; Giovati, Laura; Conti, Stefania; Magliani, Walter; Santinoli, Claudia; Polonelli, Luciano

    2016-08-01

    In recent years, the increase of invasive fungal infections and the emergence of antifungal resistance stressed the need for new antifungal drugs. Peptides have shown to be good candidates for the development of alternative antimicrobial agents through high-throughput screening, and subsequent optimization according to a rational approach. This review presents a brief overview on antifungal natural peptides of different sources (animals, plants, micro-organisms), peptide fragments derived by proteolytic cleavage of precursor physiological proteins (cryptides), synthetic unnatural peptides and peptide derivatives. Antifungal peptides are schematically reported based on their structure, antifungal spectrum and reported effects. Natural or synthetic peptides and their modified derivatives may represent the basis for new compounds active against fungal infections. PMID:27502155

  10. The synergistic potential of the azole fungicides prochloraz and propiconazole toward a short α-cypermethrin pulse increases over time in Daphnia magna.

    PubMed

    Kretschmann, Andreas; Gottardi, Michele; Dalhoff, Kristoffer; Cedergreen, Nina

    2015-05-01

    Pyrethroid insecticides are highly toxic to non-target aquatic invertebrates. Their high toxicity is synergized when co-occurring with azole fungicides in the aquatic environment. Little is known about the importance of synergy, when pyrethroids only occur during a short pulse of a few hours, as it is likely to happen in the environment, nor about the persistence of synergy over time. This study analyzed the synergistic potential of the fungicides propiconazole and prochloraz toward Daphnia magna, when exposed to a pulse (7.2 h) of α-cypermethrin at different concentrations (average pulse concentrations 0.07-11 nM). Immobilization was monitored during exposure and a subsequent recovery period (87.5h) with and without continuous co-exposure to the azoles (1.4 and 1.7 μM, respectively). EC50 values for immobilization decreased exponentially over time with a higher rate in the presence of the azoles. EC50 values for α-cypermethrin determined at the end of the experiment were 3.3±0.5 nM in the absence of azoles and 0.26±0.04, and 0.08±0.01 nM in the presence of propiconazole and prochloraz, respectively. The synergistic potential of the azoles was strongly dependent on time: no synergism could be detected during the pulse, but with azole co-exposure EC50 values decreased during the recovery period by a factor of up to 13 (propiconazole) and 61 (prochloraz) compared to values without azole exposure. Such high synergistic ratios have not been reported for pesticide mixtures in literature before. Our findings highlight that a pulse of the pyrethroid α-cypermethrin is synergized far beyond the actual pulse and beyond standardized test durations. Long post-exposure times are therefore mandatory in order to capture full synergism. PMID:25797530

  11. The synergistic potential of the azole fungicides prochloraz and propiconazole toward a short α-cypermethrin pulse increases over time in Daphnia magna.

    PubMed

    Kretschmann, Andreas; Gottardi, Michele; Dalhoff, Kristoffer; Cedergreen, Nina

    2015-05-01

    Pyrethroid insecticides are highly toxic to non-target aquatic invertebrates. Their high toxicity is synergized when co-occurring with azole fungicides in the aquatic environment. Little is known about the importance of synergy, when pyrethroids only occur during a short pulse of a few hours, as it is likely to happen in the environment, nor about the persistence of synergy over time. This study analyzed the synergistic potential of the fungicides propiconazole and prochloraz toward Daphnia magna, when exposed to a pulse (7.2 h) of α-cypermethrin at different concentrations (average pulse concentrations 0.07-11 nM). Immobilization was monitored during exposure and a subsequent recovery period (87.5h) with and without continuous co-exposure to the azoles (1.4 and 1.7 μM, respectively). EC50 values for immobilization decreased exponentially over time with a higher rate in the presence of the azoles. EC50 values for α-cypermethrin determined at the end of the experiment were 3.3±0.5 nM in the absence of azoles and 0.26±0.04, and 0.08±0.01 nM in the presence of propiconazole and prochloraz, respectively. The synergistic potential of the azoles was strongly dependent on time: no synergism could be detected during the pulse, but with azole co-exposure EC50 values decreased during the recovery period by a factor of up to 13 (propiconazole) and 61 (prochloraz) compared to values without azole exposure. Such high synergistic ratios have not been reported for pesticide mixtures in literature before. Our findings highlight that a pulse of the pyrethroid α-cypermethrin is synergized far beyond the actual pulse and beyond standardized test durations. Long post-exposure times are therefore mandatory in order to capture full synergism.

  12. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time.

  13. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time. PMID:26803804

  14. The antifungal action of dandruff shampoos.

    PubMed

    Bulmer, A C; Bulmer, G S

    1999-01-01

    The disease commonly known as "dandruff" is caused by numerous host factors in conjunction with the normal flora yeast Malassezia furfur (Pityrosporum ovale). Indeed, clinical studies have shown that administration of antifungal agents correlates with an improved clinical condition. Almost all commercially available hair shampoos publicize that they contain some form of antifungal agent(s). However, few studies have been published in which antifungal activity of commercially available hair shampoos have been contrasted experimentally. In this study six commercially available shampoos (in the Philippines) were assessed for antifungal activity against a human (dandruff) isolate of M. furfur: (a) Head & Shoulders (Proctor & Gamble); (b) Gard Violet (Colgate-Palmolive); (c) Nizoral 1% (Janssen); (d) Nizoral 2% (Janssen); (e) Pantene Blue (Proctor & Gamble); and (f) Selsun Blue (Abbott). The results demonstrated that all six of the assayed hair shampoos have some antifungal effect on the test yeast. However, there was consider variation in potency of antifungal activity. Nizoral 1% and Nizoral 2% shampoo preparations were the most effective. The 1% Nizoral shampoo was consistently 10X better at killing yeast cells than the next closest rival shampoo. The 2% Nizoral shampoo was 10X better than the Nizoral 1% product and 100 times better than any of the other products assayed. The study demonstrated that shampoos containing a proven antifungal compound were the most effective in controlling the causative yeast.

  15. Antifungal properties of halofumarate esters.

    PubMed

    Gershon, H; Shanks, L

    1978-04-01

    Alkyl esters (C1--C4) of the four halofumaric acids were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes at pH 5.6 and 7.0 in the absence and presence of 10% beef serum in Sabouraud dextrose agar. The most toxic compound to each organism was: C. albicans, ethyl iodofumarate (0.054 mmole/liter); A. niger, methyl bromofumarate (0.090 mmole/liter); M. mucedo, methyl fluorofumarate (0.037 mmole/liter); and T. mentagrophytes, ethyl iodofumarate (0.020 mmole/liter). The order of overall activity of the six most toxic compounds was: ethyl iodofumarate greater than ethyl chlorofumarate greater than methyl iodofumarate = methyl bromofumarate greater than methyl chlorofumarate greater than bromofumarate.

  16. Laboratory tests of antifungal drugs.

    PubMed Central

    Holt, R J

    1975-01-01

    The procedures evolved in the author's laboratory over the past 20 years for the microbiological assessment of antifungal drugs are described; methods are detailed for the estimation of the sensitivity of pathogenic fungi to therapeutic agents and for the assay of those agents in body fluids. The preparation and maintenance of stock reference solutions of the drugs, the culture media used, and the incubation temperature and time are discussed. Sensitivity tests by paper disc and by liquid titration for minimal inhibitory and cidal concentrations estimated are described, and the importance of standardized initial inocula is emphasized. Two groups of assay procedures are given, the liquid dilution and the agar diffusion methods, and suitable indicator organisms for both methods are named. The paper concludes with a discussion on the problem of differential assays when two antimycotic agents are in simultaneous clinical use. Images PMID:765359

  17. Antifungal proteins: More than antimicrobials?

    PubMed Central

    Hegedüs, Nikoletta; Marx, Florentine

    2013-01-01

    Antimicrobial proteins (AMPs) are widely distributed in nature. In higher eukaryotes, AMPs provide the host with an important defence mechanism against invading pathogens. AMPs of lower eukaryotes and prokaryotes may support successful competition for nutrients with other microorganisms of the same ecological niche. AMPs show a vast variety in structure, function, antimicrobial spectrum and mechanism of action. Most interestingly, there is growing evidence that AMPs also fulfil important biological functions other than antimicrobial activity. The present review focuses on the mechanistic function of small, cationic, cysteine-rich AMPs of mammals, insects, plants and fungi with antifungal activity and specifically aims at summarizing current knowledge concerning additional biological properties which opens novel aspects for their future use in medicine, agriculture and biotechnology. PMID:23412850

  18. Toxicokinetic-toxicodynamic modelling of survival of Gammarus pulex in multiple pulse exposures to propiconazole: model assumptions, calibration data requirements and predictive power.

    PubMed

    Nyman, Anna-Maija; Schirmer, Kristin; Ashauer, Roman

    2012-10-01

    Toxicokinetic-toxicodynamic (TKTD) models quantify the time-course of internal concentration, which is defined by uptake, elimination and biotransformation (TK), and the processes which lead to the toxic effects (TD). TKTD models show potential in predicting pesticide effects in fluctuating concentrations, but the data requirements and validity of underlying model assumptions are not known. We calibrated TKTD models to predict survival of Gammarus pulex in propiconazole exposure and investigated the data requirements. In order to assess the need of TK in survival models, we included or excluded simulated internal concentrations based on pre-calibrated TK. Adding TK did not improve goodness of fits. Moreover, different types of calibration data could be used to model survival, which might affect model parameterization. We used two types of data for calibration: acute toxicity (standard LC50, 4 d) or pulsed toxicity data (total length 10 d). The calibration data set influenced how well the survival in the other exposure scenario was predicted (acute to pulsed scenario or vice versa). We also tested two contrasting assumptions in ecotoxicology: stochastic death and individual tolerance distribution. Neither assumption fitted to data better than the other. We observed in 10-d toxicity experiments that pulsed treatments killed more organisms than treatments with constant concentration. All treatments received the same dose, i.e. the time-weighted average concentration was equal. We studied mode of toxic action of propiconazole and it likely acts as a baseline toxicant in G. pulex during 10-days of exposure for the endpoint survival.

  19. Topical antifungals for seborrhoeic dermatitis

    PubMed Central

    Okokon, Enembe O; Verbeek, Jos H; Ruotsalainen, Jani H; Ojo, Olumuyiwa A; Bakhoya, Victor Nyange

    2015-01-01

    Background Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy. Objectives To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults. A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS. Search methods We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials. Selection criteria Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life. Data collection and analysis Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high. Main results We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies. Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141

  20. Antifungal susceptibility of Malassezia pachydermatis biofilm.

    PubMed

    Figueredo, Luciana A; Cafarchia, Claudia; Otranto, Domenico

    2013-11-01

    Antifungal resistance has been associated with biofilm formation in many microorganisms, but not yet in Malassezia pachydermatis. This saprophytic yeast can cause otitis and dermatitis in dogs and has emerged as an important human pathogen, responsible for systemic infections in neonates in intensive care units. This study aims to evaluate the in vitro antifungal susceptibility of M. pachydermatis strains, in both their planktonic and sessile forms, to fluconazole, miconazole, ketoconazole, itraconazole, posaconazole, terbinafine and voriconazole using the XTT assay and Clinical and Laboratory Standards Institute (CLSI) microdilution method. The minimum inhibitory concentration (MIC) values recorded for each drug were significantly higher for sessile cells relative to planktonic cells to the extent that ≥ 90% of M. pachydermatis strains in their sessile form were classified as resistant to all antifungal agents tested. Data suggest that M. pachydermatis biofilm formation is associated with antifungal resistance, paving the way towards investigating drug resistance mechanisms in Malassezia spp. PMID:23834283

  1. Antifungal effect of some spice hydrosols.

    PubMed

    Boyraz, Nuh; Ozcan, Musa

    2005-12-01

    The antifungal effects of rosemary, cumin, sater (savory), basil and pickling herb hydrosols were investigated against Rhizoctonia solani, Fusarium oxysporum f. sp tulipae, Botrytis cinerea and Alternaria citri. Hydrosols of sater and pickling herb showed the most relevant fungicidal activity.

  2. Antifungal activities of some indole derivatives.

    PubMed

    Xu, Hui; Wang, Qin; Yang, Wen-Bin

    2010-01-01

    Nine indole derivatives were evaluated in vitro against Fusarium graminearum, Alternaria alternata, Helminthosporium sorokinianum, Pyricularia oryzae, Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. cucumarinum, and Alternaria brassicae. Most of the compounds were found to possess antifungal activities. Especially compounds 2, 5, 8, and 9 exhibited broad-spectrum antifungal activities against the above-mentioned seven phytopathogenic fungi, and showed more potent activities than hymexazole, a commercial agricultural fungicide. PMID:20737910

  3. ASDCD: antifungal synergistic drug combination database.

    PubMed

    Chen, Xing; Ren, Biao; Chen, Ming; Liu, Ming-Xi; Ren, Wei; Wang, Quan-Xin; Zhang, Li-Xin; Yan, Gui-Ying

    2014-01-01

    Finding effective drugs to treat fungal infections has important clinical significance based on high mortality rates, especially in an immunodeficient population. Traditional antifungal drugs with single targets have been reported to cause serious side effects and drug resistance. Nowadays, however, drug combinations, particularly with respect to synergistic interaction, have attracted the attention of researchers. In fact, synergistic drug combinations could simultaneously affect multiple subpopulations, targets, and diseases. Therefore, a strategy that employs synergistic antifungal drug combinations could eliminate the limitations noted above and offer the opportunity to explore this emerging bioactive chemical space. However, it is first necessary to build a powerful database in order to facilitate the analysis of drug combinations. To address this gap in our knowledge, we have built the first Antifungal Synergistic Drug Combination Database (ASDCD), including previously published synergistic antifungal drug combinations, chemical structures, targets, target-related signaling pathways, indications, and other pertinent data. Its current version includes 210 antifungal synergistic drug combinations and 1225 drug-target interactions, involving 105 individual drugs from more than 12,000 references. ASDCD is freely available at http://ASDCD.amss.ac.cn.

  4. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    PubMed Central

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

  5. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action.

    PubMed

    Currie, Richard A; Peffer, Richard C; Goetz, Amber K; Omiecinski, Curtis J; Goodman, Jay I

    2014-07-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA.

  6. Antifungal drug discovery: the process and outcomes

    PubMed Central

    Calderone, Richard; Sun, Nuo; Gay-Andrieu, Francoise; Groutas, William; Weerawarna, Pathum; Prasad, Sridhar; Alex, Deepu; Li, Dongmei

    2014-01-01

    New data suggest that the global incidence of several types of fungal diseases have traditionally been under-documented. Of these, mortality caused by invasive fungal infections remains disturbingly high, equal to or exceeding deaths caused by drug-resistant tuberculosis and malaria. It is clear that basic research on new antifungal drugs, vaccines and diagnostic tools is needed. In this review, we focus upon antifungal drug discovery including in vitro assays, compound libraries and approaches to target identification. Genome mining has made it possible to identify fungal-specific targets; however, new compounds to these targets are apparently not in the antimicrobial pipeline. We suggest that ‘repurposing’ compounds (off patent) might be a more immediate starting point. Furthermore, we examine the dogma on antifungal discovery and suggest that a major thrust in technologies such as structural biology, homology modeling and virtual imaging is needed to drive discovery. PMID:25046525

  7. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the...

  8. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the...

  9. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the...

  10. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the...

  11. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the...

  12. Mutation Spectrum Induced by Conazole Fungicides in LacI Transgenic C57BL/6 Mouse Liver.

    EPA Science Inventory

    Conazoles are antifungal agents used in both agricultural and pharmaceutical settings. Some conazoles, including propiconazole and triadimefon, induce hepatocellular tumors in mice, while other conazoles do not. We reported in a previous study that both propiconazole and triadime...

  13. Cinnamaldehyde and its derivatives, a novel class of antifungal agents.

    PubMed

    Shreaz, Sheikh; Wani, Waseem A; Behbehani, Jawad M; Raja, Vaseem; Irshad, Md; Karched, Maribasappa; Ali, Intzar; Siddiqi, Weqar A; Hun, Lee Ting

    2016-07-01

    The last few decades have seen an alarming rise in fungal infections, which currently represent a global health threat. Despite extensive research towards the development of new antifungal agents, only a limited number of antifungal drugs are available in the market. The routinely used polyene agents and many azole antifungals are associated with some common side effects such as severe hepatotoxicity and nephrotoxicity. Also, antifungal resistance continues to grow and evolve and complicate patient management, despite the introduction of new antifungal agents. This suitation requires continuous attention. Cinnamaldehyde has been reported to inhibit bacteria, yeasts, and filamentous molds via the inhibition of ATPases, cell wall biosynthesis, and alteration of membrane structure and integrity. In this regard, several novel cinnamaldehyde derivatives were synthesized with the claim of potential antifungal activities. The present article describes antifungal properties of cinnamaldehyde and its derivatives against diverse classes of pathogenic fungi. This review will provide an overview of what is currently known about the primary mode of action of cinnamaldehyde. Synergistic approaches for boosting the effectiveness of cinnamaldehyde and its derivatives have been highlighted. Also, a keen analysis of the pharmacologically active systems derived from cinnamaldehyde has been discussed. Finally, efforts were made to outline the future perspectives of cinnamaldehyde-based antifungal agents. The purpose of this review is to provide an overview of current knowledge about the antifungal properties and antifungal mode of action of cinnamaldehyde and its derivatives and to identify research avenues that can facilitate implementation of cinnamaldehyde as a natural antifungal. PMID:27259370

  14. Evaluation of antifungal combination against Cryptococcus spp.

    PubMed

    Reichert-Lima, Franqueline; Busso-Lopes, Ariane F; Lyra, Luzia; Peron, Isabela Haddad; Taguchi, Hideaki; Mikami, Yuzuru; Kamei, Katsuiko; Moretti, Maria Luiza; Schreiber, Angelica Z

    2016-09-01

    The second cause of death among systemic mycoses, cryptococcosis treatment represents a challenge since that 5-flucytosine is not currently available in Brazil. Looking for alternatives, this study evaluated antifungal agents, alone and combined, correlating susceptibility to genotypes. Eighty Cryptococcus clinical isolates were genotyped by URA5 gene restriction fragment length polymorphism. Antifungal susceptibility was assessed following CLSI-M27A3 for amphotericin (AMB), 5-flucytosine (5FC), fluconazole (FCZ), voriconazole (VRZ), itraconazole (ITZ) and terbinafine (TRB). Drug interaction chequerboard assay evaluated: AMB + 5FC, AMB + FCZ, AMB + TRB and FCZ + TRB. Molecular typing divided isolates into 14 C. deuterogattii (VGII) and C. neoformans isolates were found to belong to genotype VNI (n = 62) and VNII (n = 4). C. neoformans VNII was significantly less susceptible than VNI (P = 0.0407) to AMB; C. deuterogattii was significantly less susceptible than VNI and VNII to VRZ (P < 0.0001). C. deuterogattii was less susceptible than C. neoformans VNI for FCZ (P = 0.0170), ITZ (P < 0.0001) and TRB (P = 0.0090). The combination FCZ + TRB showed 95.16% of synergistic effect against C. neoformans genotype VNI isolates and all combinations showed 100% of synergism against genotype VNII isolates, suggesting the relevance of cryptococcal genotyping as it is widely known that the various genotypes (now species) have significant impact in antifungal susceptibilities and clinical outcome. In difficult-to-treat cryptococcosis, terbinafine and different antifungal combinations might be alternatives to 5FC. PMID:27135278

  15. Antifungal activity of ajoene derived from garlic.

    PubMed

    Yoshida, S; Kasuga, S; Hayashi, N; Ushiroguchi, T; Matsuura, H; Nakagawa, S

    1987-03-01

    The antifungal activity of six fractions derived from garlic was investigated in an in vitro system. Ajoene had the strongest activity in these fractions. The growth of both Aspergillus niger and Candida albicans was inhibited by ajoene at less than 20 micrograms/ml.

  16. Antifungal activity of Cynara scolymus L. extracts.

    PubMed

    Zhu, X F; Zhang, H X; Lo, R

    2005-01-01

    Chloroform, ethanol and ethyl acetate extracts of Cynara scolymus L. leaves, heads and stems were tested for their antifungal activity using the agar-well diffusion assay technique. The leaves extracts and the ethanol fractions were found to be the most effective extract against all the tested organisms.

  17. Efflux-Mediated Antifungal Drug Resistance†

    PubMed Central

    Cannon, Richard D.; Lamping, Erwin; Holmes, Ann R.; Niimi, Kyoko; Baret, Philippe V.; Keniya, Mikhail V.; Tanabe, Koichi; Niimi, Masakazu; Goffeau, Andre; Monk, Brian C.

    2009-01-01

    Summary: Fungi cause serious infections in the immunocompromised and debilitated, and the incidence of invasive mycoses has increased significantly over the last 3 decades. Slow diagnosis and the relatively few classes of antifungal drugs result in high attributable mortality for systemic fungal infections. Azole antifungals are commonly used for fungal infections, but azole resistance can be a problem for some patient groups. High-level, clinically significant azole resistance usually involves overexpression of plasma membrane efflux pumps belonging to the ATP-binding cassette (ABC) or the major facilitator superfamily class of transporters. The heterologous expression of efflux pumps in model systems, such Saccharomyces cerevisiae, has enabled the functional analysis of efflux pumps from a variety of fungi. Phylogenetic analysis of the ABC pleiotropic drug resistance family has provided a new view of the evolution of this important class of efflux pumps. There are several ways in which the clinical significance of efflux-mediated antifungal drug resistance can be mitigated. Alternative antifungal drugs, such as the echinocandins, that are not efflux pump substrates provide one option. Potential therapeutic approaches that could overcome azole resistance include targeting efflux pump transcriptional regulators and fungal stress response pathways, blockade of energy supply, and direct inhibition of efflux pumps. PMID:19366916

  18. Antifungal prophylaxis during neutropenia and immunodeficiency.

    PubMed Central

    Lortholary, O; Dupont, B

    1997-01-01

    Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses. PMID:9227863

  19. Oral Antifungal Drugs in the Treatment of Dermatomycosis.

    PubMed

    Tsunemi, Yuichiro

    2016-01-01

    Oral antifungal drugs are used primarily to treat tinea unguium; however, they are also useful for other types of tinea. For example, a combination of topical and oral antifungal drugs is effective in hyperkeratotic tinea pedis that is unresponsive to topical monotherapy. In cases of tinea facialis adjacent to the eyes, ears, or mouth, or widespread tinea corporis, or tinea cruris involving the complex skin folds of the external genitalia, it is difficult to apply topical drugs to all the lesions; therefore, oral antifungal drugs are necessary. Oral antifungal drugs are also useful not only for tinea but for widespread pityriasis versicolor and Malassezia folliculitis, candidal onychomycosis, and candidal paronychia and onychia. Topical antifungal drugs are in fact unsuitable for some mycoses. In tinea capitis, for example, irritation by topical drugs is likely to enhance inflammation; therefore, oral antifungal drug monotherapy is preferable. In interdigital tinea pedis with erosion or contact dermatitis, topical drugs are difficult to use because they tend to cause irritant dermatitis, resulting in exacerbation of the condition. In such cases, treatment should begin with a combination of topical corticosteroid therapy and oral antifungal drugs active against dermatophytes. Topical antifungal drugs are used after the complications resolve. A combination of topical and oral antifungal drugs can shorten the treatment period, thus improving patient adherence to topical treatment. Oral antifungal drugs are useful because of their wide range of applications in the treatment of dermatomycosis. PMID:27251319

  20. An antifungal peptide from the coconut.

    PubMed

    Wang, H X; Ng, T B

    2005-12-01

    A chromatographic procedure consisting of ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose, and gel filtration by fast performance liquid chromatography on Supedex 75 was utilized to isolate a 10 kDa antifungal peptide from coconut flesh. The peptide was unadsorbed on DEAE-cellulose, but adsorbed on Affi-gel blue gel and CM-cellulose. It displayed antifungal activity against Fusarium oxysporum, Mycosphaerella arachidicola and Physalospora piricola. The IC50 values of its inhibitory activities on mycelial growth in M. arachidicola and HIV-1 reverse transcriptase activity were respectively 1.2 and 52.5 microM.

  1. Photodynamic therapy as an antifungal treatment

    PubMed Central

    LIANG, YI; LU, LI-MING; CHEN, YONG; LIN, YOU-KUN

    2016-01-01

    Photodynamic therapy (PDT) involves the systemic or topical application of a photosensitizer (PS), alongside the selective illumination of the target lesion with light of an appropriate wavelength, in order to promote localized oxidative photodamage and subsequent cell death. Numerous studies have demonstrated that PDT is highly effective in the destruction of fungi in vitro. The mechanism underlying the effects of PDT results from the photons of visible light of an appropriate wavelength interacting with the intracellular molecules of the PS. Reactive species are produced as a result of the oxidative stress caused by the interaction between the visible light and the biological tissue. At present, no antifungal treatment based on PDT has been licensed. However, antifungal PDT is emerging as an area of interest for research. PMID:27347012

  2. Antifungal activity of 10 Guadeloupean plants.

    PubMed

    Biabiany, Murielle; Roumy, Vincent; Hennebelle, Thierry; François, Nadine; Sendid, Boualem; Pottier, Muriel; Aliouat, El Moukhtar; Rouaud, Isabelle; Lohézic-Le Dévéhat, Françoise; Joseph, Henry; Bourgeois, Paul; Sahpaz, Sevser; Bailleul, François

    2013-11-01

    Screening of the antifungal activities of ten Guadeloupean plants was undertaken to find new extracts and formulations against superficial mycoses such as onychomycosis, athlete's foot, Pityriasis versicolor, as well as the deep fungal infection Pneumocystis pneumonia. For the first time, the CMI of these plant extracts [cyclohexane, ethanol and ethanol/water (1:1, v/v)] was determined against five dermatophytes, five Candida species, Scytalidium dimidiatum, a Malassezia sp. strain and Pneumocystis carinii. Cytotoxicity tests of the most active extracts were also performed on an HaCat keratinocyte cell line. Results suggest that the extracts of Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis have interesting activities and could be good candidates for developing antifungal formulations. PMID:23280633

  3. A new antifungal coumarin from Clausena excavata.

    PubMed

    Kumar, Ramashish; Saha, Aniruddha; Saha, Dipanwita

    2012-01-01

    A new γ-lactone coumarin, named as excavarin-A, showing antifungal activity was isolated from the leaves of Clausena excavata by bioassay guided fractionation method. The structure was elucidated by spectroscopic data analysis and identified as 7((2E)-4(4,5-dihydro-3-methylene-2-oxo-5-furanyl)-3-methylbut-2-enyloxy) coumarin. Minimum inhibitory concentration (MIC) was determined against fifteen fungal strains pathogenic against plants and human. The least MIC was recorded against the human pathogen, Candida tropicalis and the plant pathogens Rhizoctonia solani and Sclerotinia sclerotiorum. Antifungal activities against the human pathogens, Aspergillus fumigatus and Mucor circinelloides and plant pathogens, Colletotrichum gloeosporioides, Lasiodiplodia theobromae, Fusarium oxysporum and Rhizopus stolonifer were stronger than that of the standard antimicrobials. PMID:22088496

  4. Econazole imprinted textiles with antifungal activity.

    PubMed

    Hossain, Mirza Akram; Lalloz, Augustine; Benhaddou, Aicha; Pagniez, Fabrice; Raymond, Martine; Le Pape, Patrice; Simard, Pierre; Théberge, Karine; Leblond, Jeanne

    2016-04-01

    In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining drug activity. Lipid microparticles were prepared and characterized by laser diffraction (3.5±0.1 μm). Using an optimized screen-printing method, microparticles were deposited on textiles, as observed by scanning electron microscopy. The drug content of textiles (97±3 μg/cm(2)) was reproducible and stable up to 4 months storage at 25 °C/65% Relative Humidity. Imprinted textiles exhibited a thermosensitive behavior, as witnessed by a fusion temperature of 34.8 °C, which enabled a larger drug release at 32 °C (temperature of the skin) than at room temperature. In vitro antifungal activity of ECN textiles was compared to commercial 1% (wt/wt) ECN cream Pevaryl®. ECN textiles maintained their antifungal activity against a broad range of Candida species as well as major dermatophyte species. In vivo, ECN textiles also preserved the antifungal efficacy of ECN on cutaneous candidiasis infection in mice. Ex vivo percutaneous absorption studies demonstrated that ECN released from pharmaceutical textiles concentrated more in the upper skin layers, where the fungal infections develop, as compared to dermal absorption of Pevaryl®. Overall, these results showed that this technology is promising to develop pharmaceutical garments textiles for the treatment of superficial fungal infections. PMID:26883854

  5. Antifungal potential of Spilanthes calva after inoculation of Piriformospora indica.

    PubMed

    Rai, M K; Varma, A; Pandey, A K

    2004-12-01

    We investigated the influence of Piriformospora indica on the antifungal principle of Spilanthes calva, a plant of high commercial value. An antifungal efficacy was shown by aqueous and petroleum ether extracts of S. calva against Fusarium oxysporum and Trichophyton mentagrophytes. The petroleum ether extract of S. calva was more effective than the aqueous extract in inoculated as well as uninoculated plants. The antifungal activity of the plant was enhanced due to the increase in spilanthol content after inoculation of P. indica. PMID:15601453

  6. Nonanoic Acid, an Antifungal Compound from Hibiscus syriacus Ggoma

    PubMed Central

    Jang, Yun-Woo; Jung, Jin-Young; Lee, In-Kyoung

    2012-01-01

    The root of Hibiscus syriacus (Malvaceae) has been used for treatment of fungal diseases such as tinea pedis (athlete's foot). In this study, we investigated the antifungal constituent of the root of Hibiscus syriacus Ggoma, which was produced by a mutation breeding using gamma ray irradiation, and compared the antifungal activity of H. syriacus Ggoma and its parent type. According to the results, the methanolic extract of H. syriacus Ggoma exhibited four times higher antifungal activity than its parent type against Trichophyton mentagrophytes. Following purification through various column chromatographies, the antifungal substance was identified as nonanoic acid on the basis of spectroscopic analysis. PMID:22870060

  7. Effects of exposure to sublethal propiconazole on the antioxidant defense system and Na+-K+-ATPase activity in brain of rainbow trout, Oncorhynchus mykiss.

    PubMed

    Li, Zhi-Hua; Zlabek, Vladimir; Grabic, Roman; Li, Ping; Machova, Jana; Velisek, Josef; Randak, Tomas

    2010-07-01

    Propiconazole (PCZ), a triazole fungicide, is widely present in the aquatic environment, but little is known regarding its chronic toxicity in the fish brain. This study assessed the effects of long-term exposure to PCZ on the antioxidant defense system and Na(+)-K(+)-ATPase activity of rainbow trout brain. Fish were exposed to sublethal concentrations of PCZ (0.2, 50, and 500 microg/l) for 7, 20, and 30 days, respectively. Oxidative stress indices (reactive oxygen species, lipid peroxidation, and carbonyl protein) and antioxidant parameters (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and reduced glutathione) were measured, as well as Na(+)-K(+)-ATPase activity. Adaptive responses to PCZ-induced stress were observed at 7 days. With prolonged exposure, significantly higher levels of oxidative indices were indicative of oxidative stress, as also were the significant inhibition of antioxidant enzyme activity and reduced glutathione content. Na(+)-K(+)-ATPase activity was significantly inhibited after prolonged exposure. Chemometrics of all parameters by principal component analysis, enabled the separation of sampled individuals into four groups with 93.39% of total accumulated variance. A low level of oxidative stress can induce the adaptive responses of the antioxidant defense system, while prolonged exposure to PCZ may lead to serious oxidative damage in fish brain. We suggest that selected biochemical markers in fish brain could be used as potential biomarkers for monitoring residual fungicides present in the aquatic environments.

  8. Identification of Antifungal Substances of Lactobacillus sakei subsp. ALI033 and Antifungal Activity against Penicillium brevicompactum Strain FI02

    PubMed Central

    Huh, Chang Ki; Hwang, Tae Yean

    2016-01-01

    This study was performed to investigate the antifungal substances and the antifungal activity against fungi of lactic acid bacteria (LAB) isolated from kimchi. LAB from kimchi in Imsil showed antifungal activity against Penicillium brevicompactum strain FI02. LAB LI031 was identified as Lactobacillus sakei subsp. Antifungal substances contained in L. sakei subsp. ALI033 culture media were unstable at high pH levels. Both, the control and proteinase K and protease treated samples showed clear zones, suggesting that the antifungal substances produced by ALI033 were non-protein substances unaffected by protesases. Both, the control and catalase showed clear zones, suggesting that the antifungal metabolite was not H2O2. The molecular weights of the antifungal substances were ≤3,000 Da. The organic acid content of crude antifungal substances produced by L. sakei subsp. ALI033 showed high concentrations of lactic acid (502.47 mg/100 g). Therefore, these results suggest that antifungal substance produced by L. sakei subsp. ALI033 is most likely due to its ability in producing organic acid. PMID:27069906

  9. Optimization of Antifungal Extracts from Ficus hirta Fruits Using Response Surface Methodology and Antifungal Activity Tests.

    PubMed

    Chen, Chuying; Wan, Chunpeng; Peng, Xuan; Chen, Yuhuan; Chen, Ming; Chen, Jinyin

    2015-01-01

    The fruits of Ficus hirta (FH) display strong antifungal activity against Penicillium italicum and Penicillium digitatum. In order to optimize the extraction conditions of antifungal extracts from FH fruit, various extraction parameters, such as ethanol concentration, extraction time, solvent to solid ratio and temperature, were chosen to identify their effects on the diameters of inhibition zones (DIZs) against these two Penicillium molds. Response surface methodology (RSM) was applied to obtain the optimal combination of these parameters. Results showed that the optimal extraction parameters for maximum antifungal activity were: 90% (v/v) ethanol concentration, 65 min extraction time, 31 mL/g solvent to solid ratio and 51 °C temperature. Under the abovementioned extraction conditions, the experimental DIZs values obtained experimentally were 57.17 ± 0.75 and 39.33 ± 0.82 mm, which were very close to the values of 57.26 and 39.29 mm predicted by the model. Further, nine kinds of phytopathogens were tested in vitro to explore the antifungal activity of the FH extracts. It was found for the first time that the FH extracts showed significant inhibition on the growth of P. italicum, A. citri, P. vexans, P. cytosporella and P. digitatum. PMID:26528961

  10. In vitro antifungal effect of human milk.

    PubMed

    Mete, Emin; Bavbek, Nüket; Dayi, Sabriye; Erkmen, Mehtap; Andiran, Fatih

    2006-01-01

    A lower incidence of infection occurs among breast-fed babies because of the presence of antibacterial, antiviral, and antiparasitic effects, but little is known about the antifungal effects to fungi other than Candida albicans. This study was undertaken to assess the antifungal effect of human milk to the fungi in the environmental air, which also may be allergenic. Milk samples were obtained from lactating mothers of healthy term infants between the 3rd and 8th days of lactation. Ninety-six Sabouraud agar petri dishes were separated into three groups, closed, and incubated in the same location after 15 minutes uncovered. The first group (group 1, n=48 dishes) was used to detect the fungal flora of the environmental air. The second group (group 2, n=24 dishes) was rubbed with a thin layer of human milk by a sterile pipette. The last group (group 3, n=24 dishes) was rubbed with 0.9% NaCIlsolution. After 7 days of incubation, the colony-forming fungal growths of all dishes were evaluated by a microbiologist who did not know the groups of the dishes. The number offungal colonies grown in human milk-rubbed dishes in group 2 was less than both of the other groups (group 1 and 3; p < 0.001 and p < 0.001, respectively). These results indicated that human milk may have antifungal effects to fungi present in the environmental air as tested by Sabouraud agar petri dishes. To prevent infections and allergic diseases, human milk must be considered the ideal food for newborns. PMID:17063672

  11. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Screening natural product extracts from National Cancer Institute Open Repository for antifungal discovery afforded hits for bioassay-guided fractionation. Upon LC-MS analysis of column fractions with antifungal activities to generate information on chemical structure, two new cyclic hexapeptides, m...

  12. Cuticular antifungals in spiders: density- and condition dependence.

    PubMed

    González-Tokman, Daniel; Ruch, Jasmin; Pulpitel, Tamara; Ponton, Fleur

    2014-01-01

    Animals living in groups face a high risk of disease contagion. In many arthropod species, cuticular antimicrobials constitute the first protective barrier that prevents infections. Here we report that group-living spiders produce cuticular chemicals which inhibit fungal growth. Given that cuticular antifungals may be costly to produce, we explored whether they can be modulated according to the risk of contagion (i.e. under high densities). For this purpose, we quantified cuticular antifungal activity in the subsocial crab spider Diaea ergandros in both natural nests and experimentally manipulated nests of varying density. We quantified the body-condition of spiders to test whether antifungal activity is condition dependent, as well as the effect of spider density on body-condition. We predicted cuticular antifungal activity to increase and body-condition to decrease with high spider densities, and that antifungal activity would be inversely related to body-condition. Contrary to our predictions, antifungal activity was neither density- nor condition-dependent. However, body-condition decreased with density in natural nests, but increased in experimental nests. We suggest that pathogen pressure is so important in nature that it maintains high levels of cuticular antifungal activity in spiders, impacting negatively on individual energetic condition. Future studies should identify the chemical structure of the isolated antifungal compounds in order to understand the physiological basis of a trade-off between disease prevention and energetic condition caused by group living, and its consequences in the evolution of sociality in spiders.

  13. Nosocomial Candidiasis: Antifungal Stewardship and the Importance of Rapid Diagnosis.

    PubMed

    Pfaller, Michael A; Castanheira, Mariana

    2016-01-01

    Candidemia and other forms of candidiasis are associated with considerable excess mortality and costs. Despite the addition of several new antifungal agents with improved spectrum and potency, the frequency of Candida infection and associated mortality have not decreased in the past two decades. The lack of rapid and sensitive diagnostic tests has led to considerable overuse of antifungal agents resulting in increased costs, selection pressure for resistance, unnecessary drug toxicity, and adverse drug interactions. Both the lack of timely diagnostic tests and emergence of antifungal resistance pose considerable problems for antifungal stewardship. Whereas antifungal stewardship with a focus on nosocomial candidiasis should be able to improve the administration of antifungal therapy in terms of drug selection, proper dose and duration, source control and de-escalation therapy, an important parameter, timeliness of antifungal therapy, remains a victim of slow and insensitive diagnostic tests. Fortunately, new proteomic and molecular diagnostic tools are improving the time to species identification and detection. In this review we will describe the potential impact that rapid diagnostic testing and antifungal stewardship can have on the management of nosocomial candidiasis.

  14. Antifungal activity of Piper diospyrifolium Kunth (Piperaceae) essential oil

    PubMed Central

    Vieira, Silvia Cristina Heredia; de Paulo, Luis Fernando; Svidzinski, Terezinha Inez Estivaleti; Dias Filho, Benedito Prado; Nakamura, Celso Vataru; de Souza, Amanda; Young, Maria Cláudia Marx; Cortez, Diógenes Aparício Garcia

    2011-01-01

    In vitro activity of the essential oil from Piper diospyrifolium leaves was tested using disk diffusion techniques. The antifungal assay showed significant potencial antifungal activity: the oil was effective against several clinical fungal strains. The majority compounds in the essential oil were identified as sesquiterpenoids by GC-MS and GC-FID techniques. PMID:24031717

  15. Cuticular Antifungals in Spiders: Density- and Condition Dependence

    PubMed Central

    González-Tokman, Daniel; Ruch, Jasmin; Pulpitel, Tamara; Ponton, Fleur

    2014-01-01

    Animals living in groups face a high risk of disease contagion. In many arthropod species, cuticular antimicrobials constitute the first protective barrier that prevents infections. Here we report that group-living spiders produce cuticular chemicals which inhibit fungal growth. Given that cuticular antifungals may be costly to produce, we explored whether they can be modulated according to the risk of contagion (i.e. under high densities). For this purpose, we quantified cuticular antifungal activity in the subsocial crab spider Diaea ergandros in both natural nests and experimentally manipulated nests of varying density. We quantified the body-condition of spiders to test whether antifungal activity is condition dependent, as well as the effect of spider density on body-condition. We predicted cuticular antifungal activity to increase and body-condition to decrease with high spider densities, and that antifungal activity would be inversely related to body-condition. Contrary to our predictions, antifungal activity was neither density- nor condition-dependent. However, body-condition decreased with density in natural nests, but increased in experimental nests. We suggest that pathogen pressure is so important in nature that it maintains high levels of cuticular antifungal activity in spiders, impacting negatively on individual energetic condition. Future studies should identify the chemical structure of the isolated antifungal compounds in order to understand the physiological basis of a trade-off between disease prevention and energetic condition caused by group living, and its consequences in the evolution of sociality in spiders. PMID:24637563

  16. Chemical modification of antifungal polyene macrolide antibiotics

    NASA Astrophysics Data System (ADS)

    Solovieva, S. E.; Olsufyeva, E. N.; Preobrazhenskaya, M. N.

    2011-02-01

    The review summarizes advances in the methods for the synthesis of polyene antibiotics (amphotericin B, partricin A, etc.) and investigations of the structure-activity relationship made in the last 15 years. State-of-the-art approaches based on the combination of the chemical synthesis and genetic engineering are considered. Emphasis is given to the design of semisynthetic antifungal agents against chemotherapy-resistant pathogens having the highest therapeutic indices. Recent results of research on the mechanisms of action of polyenes are outlined.

  17. Antifungal ether diglycosides from Matayba guianensis Aublet.

    PubMed

    de Assis, Polyana A; Theodoro, Phellipe N E T; de Paula, José E; Araújo, Ana J; Costa-Lotufo, Letícia V; Michel, Sylvie; Grougnet, Raphaël; Kritsanida, Marina; Espindola, Laila S

    2014-03-01

    Since the 1960s, fungal infections have become a major worldwide public health problem. Antifungal treatments have many limitations, such as toxicity and resistance. Matayba guianensis Aublet (Sapindaceae) was chemically investigated as part of our ongoing search for lead molecules against fungi in the Brazilian Cerrado biome. The ethanolic extract of M. guianensis root bark revealed the presence of two previously unreported ether diglycosides: matayoside E (1) and F (2) with anti Candida activity, along with two known compounds: cupanioside (3) and stigmasterol (4).

  18. Synthesis and investigation of novel benzimidazole derivatives as antifungal agents.

    PubMed

    Chandrika, Nishad Thamban; Shrestha, Sanjib K; Ngo, Huy X; Garneau-Tsodikova, Sylvie

    2016-08-15

    The rise and emergence of resistance to antifungal drugs by diverse pathogenic fungal strains have resulted in an increase in demand for new antifungal agents. Various heterocyclic scaffolds with different mechanisms of action against fungi have been investigated in the past. Herein, we report the synthesis and antifungal activities of 18 alkylated mono-, bis-, and trisbenzimidazole derivatives, their toxicities against mammalian cells, as well as their ability to induce reactive oxygen species (ROS) in yeast cells. Many of our bisbenzimidazole compounds exhibited moderate to excellent antifungal activities against all tested fungal strains, with MIC values ranging from 15.6 to 0.975μg/mL. The fungal activity profiles of our bisbenzimidazoles were found to be dependent on alkyl chain length. Our most potent compounds were found to display equal or superior antifungal activity when compared to the currently used agents amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole against many of the strains tested. PMID:27301676

  19. Advances in synthetic approach to and antifungal activity of triazoles

    PubMed Central

    Kumar, Nitin; Drabu, Sushma; Sharma, Pramod Kumar

    2011-01-01

    Summary Several five membered ring systems, e.g., triazole, oxadiazole dithiazole and thiadiazole with three heteroatoms at symmetrical or asymmetrical positions have been studied because of their interesting pharmacological properties. In this article our emphasis is on synthetic development and pharmacological activity of the triazole moiety which exhibit a broad spectrum of pharmacological activity such as antifungal, antibacterial, anti-inflammatory and anticancer etc. Triazoles have increased our ability to treat many fungal infections, for example, candidiasis, cryptococcal meningitis, aspergillosis etc. However, mortality due to these infections even with antifungal therapy is still unacceptably high. Therefore, the development of new antifungal agents targeting specific fungal structures or functions is being actively pursued. Rapid developments in molecular mycology have led to a concentrated search for more target antifungals. Although we are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases, the options for treatment will have greatly expanded. PMID:21804864

  20. Microbial Biotransformation to Obtain New Antifungals

    PubMed Central

    Bianchini, Luiz F.; Arruda, Maria F. C.; Vieira, Sergio R.; Campelo, Patrícia M. S.; Grégio, Ana M. T.; Rosa, Edvaldo A. R.

    2015-01-01

    Antifungal drugs belong to few chemical groups and such low diversity limits the therapeutic choices. The urgent need of innovative options has pushed researchers to search new bioactive molecules. Literature regarding the last 15 years reveals that different research groups have used different approaches to achieve such goal. However, the discovery of molecules with different mechanisms of action still demands considerable time and efforts. This review was conceived to present how Pharmaceutical Biotechnology might contribute to the discovery of molecules with antifungal properties by microbial biotransformation procedures. Authors present some aspects of (1) microbial biotransformation of herbal medicines and food; (2) possibility of major and minor molecular amendments in existing molecules by biocatalysis; (3) methodological improvements in processes involving whole cells and immobilized enzymes; (4) potential of endophytic fungi to produce antimicrobials by bioconversions; and (5) in silico research driving to the improvement of molecules. All these issues belong to a new conception of transformation procedures, so-called “green chemistry,” which aims the highest possible efficiency with reduced production of waste and the smallest environmental impact. PMID:26733974

  1. Antifungal Quinoline Alkaloids from Waltheria indica.

    PubMed

    Cretton, Sylvian; Dorsaz, Stéphane; Azzollini, Antonio; Favre-Godal, Quentin; Marcourt, Laurence; Ebrahimi, Samad Nejad; Voinesco, Francine; Michellod, Emilie; Sanglard, Dominique; Gindro, Katia; Wolfender, Jean-Luc; Cuendet, Muriel; Christen, Philippe

    2016-02-26

    Chemical investigation of a dichloromethane extract of the aerial parts of Waltheria indica led to the isolation and characterization of five polyhydroxymethoxyflavonoids, namely, oxyanin A (1), vitexicarpin (3), chrysosplenol E (4), flindulatin (5), 5-hydroxy-3,7,4'-trimethoxyflavone (6), and six quinolone alkaloids, waltheriones M-Q (2, 7, 8, 10, 11) and 5(R)-vanessine (9). Among these, compounds 2, 7, 8, 10, and 11 have not yet been described in the literature. Their chemical structures were established by means of spectroscopic data interpretation including (1)H and (13)C, HSQC, HMBC, COSY, and NOESY NMR experiments and UV, IR, and HRESIMS. The absolute configurations of the compounds were established by ECD. The isolated constituents and 10 additional quinoline alkaloids previously isolated from the roots of the plant were evaluated for their in vitro antifungal activity against the human fungal pathogen Candida albicans, and 10 compounds (7, 9, 11-16, 18, 21) showed growth inhibitory activity on both planktonic cells and biofilms (MIC ≤ 32 μg/mL). Their spectrum of activity against other pathogenic Candida species and their cytotoxicity against human HeLa cells were also determined. In addition, the cytological effect of the antifungal isolated compounds on the ultrastructure of C. albicans was evaluated by transmission electron microscopy.

  2. Antifungal Th Immunity: Growing up in Family

    PubMed Central

    Borghi, Monica; Renga, Giorgia; Puccetti, Matteo; Oikonomou, Vasileios; Palmieri, Melissa; Galosi, Claudia; Bartoli, Andrea; Romani, Luigina

    2014-01-01

    Fungal diseases represent an important paradigm in immunology since they can result from either the lack of recognition or over-activation of the inflammatory response. Current understanding of the pathophysiology underlying fungal infections and diseases highlights the multiple cell populations and cell-signaling pathways involved in these conditions. A systems biology approach that integrates investigations of immunity at the systems-level is required to generate novel insights into this complexity and to decipher the dynamics of the host–fungus interaction. It is becoming clear that a three-way interaction between the host, microbiota, and fungi dictates the types of host–fungus relationship. Tryptophan metabolism helps support this interaction, being exploited by the mammalian host and commensals to increase fitness in response to fungi via resistance and tolerance mechanisms of antifungal immunity. The cellular and molecular mechanisms that provide immune homeostasis with the fungal biota and its possible rupture in fungal infections and diseases will be discussed within the expanding role of antifungal Th cell responses. PMID:25360137

  3. Mechanisms of echinocandin antifungal drug resistance

    PubMed Central

    Perlin, David S.

    2015-01-01

    Fungal infections due to Candida and Aspergillus species cause extensive morbidity and mortality, especially among immunosuppressed patients, and antifungal therapy is critical to patient management. Yet only a few drug classes are available to treat invasive fungal diseases, and this problem is compounded by the emergence of antifungal resistance. Echinocandin drugs are the preferred choice to treat candidiasis. They are the first cell wall–active agents and target the fungal-specific enzyme glucan synthase, which catalyzes the biosynthesis of β-1,3-glucan, a key cell wall polymer. Therapeutic failures occur rarely among common Candida species, with the exception of Candida glabrata, which are frequently multidrug resistant. Echinocandin resistance in susceptible species is always acquired during therapy. The mechanism of resistance involves amino acid changes in hot-spot regions of Fks subunits of glucan synthase, which decrease the sensitivity of the enzyme to drug. Cellular stress response pathways lead to drug adaptation, which promote the formation of resistant fks strains. Clinical factors promoting echinocandin resistance include empiric therapy, prophylaxis, gastrointestinal reservoirs, and intra-abdominal infections. A better understanding of the echinocandin resistance mechanism, along with cellular and clinical factors promoting resistance, will promote more effective strategies to overcome and prevent echinocandin resistance. PMID:26190298

  4. Synergistic Antifungal Effect of Glabridin and Fluconazole

    PubMed Central

    Liu, Wei; Li, Li Ping; Zhang, Jun Dong; Li, Qun; Shen, Hui; Chen, Si Min; He, Li Juan; Yan, Lan; Xu, Guo Tong; An, Mao Mao; Jiang, Yuan Ying

    2014-01-01

    The incidence of invasive fungal infections is increasing in recent years. The present study mainly investigated glabridin (Gla) alone and especially in combination with fluconazole (FLC) against Cryptococcus neoformans and Candida species (Candida albicans, Candida tropicalis, Candida krusei, Candida parapsilosis and Candida Glabratas) by different methods. The minimal inhibitory concentration (MIC) and the minimal fungicidal concentration (MFC) indicated that Gla possessed a broad-spectrum antifungal activity at relatively high concentrations. After combining with FLC, Gla exerted a potent synergistic effect against drug-resistant C. albicans and C. tropicalis at lower concentrations when interpreted by fractional inhibitory concentration index (FICI). Disk diffusion test and time-killing test confirming the synergistic fungicidal effect. Cell growth tests suggested that the synergistic effect of the two drugs depended more on the concentration of Gla. The cell envelop damage including a significant decrease of cell size and membrane permeability increasing were found after Gla treatment. Together, our results suggested that Gla possessed a synergistic effect with FLC and the cell envelope damage maybe contributed to the synergistic effect, which providing new information for developing novel antifungal agents. PMID:25058485

  5. Microbial Biotransformation to Obtain New Antifungals.

    PubMed

    Bianchini, Luiz F; Arruda, Maria F C; Vieira, Sergio R; Campelo, Patrícia M S; Grégio, Ana M T; Rosa, Edvaldo A R

    2015-01-01

    Antifungal drugs belong to few chemical groups and such low diversity limits the therapeutic choices. The urgent need of innovative options has pushed researchers to search new bioactive molecules. Literature regarding the last 15 years reveals that different research groups have used different approaches to achieve such goal. However, the discovery of molecules with different mechanisms of action still demands considerable time and efforts. This review was conceived to present how Pharmaceutical Biotechnology might contribute to the discovery of molecules with antifungal properties by microbial biotransformation procedures. Authors present some aspects of (1) microbial biotransformation of herbal medicines and food; (2) possibility of major and minor molecular amendments in existing molecules by biocatalysis; (3) methodological improvements in processes involving whole cells and immobilized enzymes; (4) potential of endophytic fungi to produce antimicrobials by bioconversions; and (5) in silico research driving to the improvement of molecules. All these issues belong to a new conception of transformation procedures, so-called "green chemistry," which aims the highest possible efficiency with reduced production of waste and the smallest environmental impact. PMID:26733974

  6. Identification of antifungal compounds produced by Lactobacillus casei AST18.

    PubMed

    Li, Hongjuan; Liu, Lu; Zhang, Shuwen; Cui, Wenming; Lv, Jiaping

    2012-08-01

    Lactobacillus casei AST18 was screened as an antifungal lactic acid bacteria which we have reported before. In this research, the antifungal properties of cell-free culture filtrate (CCF) from L. casei AST18 were detected, and the antifungal compounds of CCF were prepared by ultrafiltration, and semi-preparative HPLC, and then determined by GC-MS. CCF was sensitive to pH and heat treatment but it was not affected by the treatment of trypsin and pepsin. Through the treatment of ultrafiltration and semi-preparative HPLC there were two parts of CCF which showed antifungal activities: part 1 and part 4. Lactic acid was identified as the main antifungal compound in part 1. In part 4, three small molecular substances were detected with GC-MS. The three potential antifungal substances were cyclo-(Leu-Pro), 2,6-diphenyl-piperidine, and 5,10-diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo[1,2-a;1',2'-d]pyrazine. The antifungal activity of L. casei AST18 was a synergistic effect of lactic acid and cyclopeptides. PMID:22580887

  7. ALTERATIONS IN mRNA GENE EXPRESSION ASSOCIATED WITH CHOLESTEROL METABOLISM, CELL CYCLE, AND OXIDATIVE STRESS INDUCED BY TRIAZOLE CONTAINING CONAZOLES IN RAT LIVER

    EPA Science Inventory

    Conazoles are fungicides used as pharmaceuticals and in agriculture. Triadimefon was hepatotoxic and induced follicular cell adenomas in the thyroid gland. In contrast,propiconazole and myclobutanil were hepatotoxic but had no effect on the thyroid gland. It was proposed that tri...

  8. Antifungal activities of ethanolic extract from Jatropha curcas seed cake.

    PubMed

    Saetae, Dolaporn; Suntornsuk, Worapot

    2010-02-01

    Phorbol ester extraction was carried out from Jatropha curcas seed cake, a by-product from the bio-diesel fuel industry. Four repeated extractions from 5 g J. curcas seed cake using 15 ml of 90% (v/v) ethanol and a shaking speed of 150 rev/min gave the highest yield of phosbol esters. The ethanolic extract of J. curcas seed cake showed antifungal activities against important phytofungal pathogens: Fusarium oxysporum, Pythium aphanidermatum, Lasiodiplodia theobromae, Curvularia lunata, Fusarium semitectum, Colletotrichum capsici and Colletotrichum gloeosporiodes. The extract contained phorbol esters mainly responsible for antifungal activities. The extract could therefore be used as an antifungal agent for agricultural applications. PMID:20208435

  9. Antifungal activity of Brevibacillus laterosporus JX-5 and characterization of its antifungal components.

    PubMed

    Jiang, Hongxia; Wang, Xiaohui; Xiao, Chengze; Wang, Weiyan; Zhao, Xu; Sui, Junkang; Sa, Rongbo; Guo, Tai L; Liu, Xunli

    2015-10-01

    The establishment of safe and effective methods for controlling fungal disease is an urgent issue in agriculture and forestry. Microbiological control of plant disease is expected to achieve better results than use of chemically derived fungicides. This study aimed to establish Brevibacillus laterosporus JX-5 as a potential microbiological control agent of poplar canker. The bacterium was isolated from the poplar rhizosphere and demonstrated significant growth inhibition of several pathogenic fungi in vitro. The antifungal components of Br. laterosporus JX-5 were isolated and identified. The fermentation broth of Br. laterosporus JX-5 and its main antifungal component, designated as component B, reduced Botryosphaeria dothidea associated canker of the excised poplar branch by 70 and 90%, respectively. Component B is considerably heat-stable, adaptable to a broad pH range, and UV-resistant. It could inhibit Bo. dothidea by permeating the fungal membrane, fracturing the nuclei, damaging the cell wall, and eventually killing the pathogenic fungus. The antifungal activity exhibited by Br. laterosporus JX-5 and its bioactive metabolic products indicate its feasibility as a potential biocontrol agent for plant diseases. PMID:26265360

  10. Antifungal combination therapy for invasive aspergillosis.

    PubMed

    Martín-Peña, Almudena; Aguilar-Guisado, Manuela; Espigado, Ildefonso; Cisneros, José Miguel

    2014-11-15

    The outcome of invasive aspergillosis (IA) continues to be associated with significant attributable mortality, especially in patients with hematological malignancies and in hematopoietic stem cell transplant recipients. In this context, antifungal combined therapy (ACT) has become an emerging strategy against IA. In an attempt to evaluate the benefits of ACT, a large number of experimental studies, clinical series, and randomized trials have been performed, with varying results. In addition, several controlled trials have been registered; however, in most cases, their final results have not been made available. In summary, there is an imbalance between the lack of published evidence regarding the benefits of ACT and its extensive and increasing use in current clinical practice, despite its associated cost. Here, we present a critical analysis of the available information regarding ACT for the treatment of IA as well as the authors' opinion with respect to its use.

  11. Overview of medically important antifungal azole derivatives.

    PubMed Central

    Fromtling, R A

    1988-01-01

    Fungal infections are a major burden to the health and welfare of modern humans. They range from simply cosmetic, non-life-threatening skin infections to severe, systemic infections that may lead to significant debilitation or death. The selection of chemotherapeutic agents useful for the treatment of fungal infections is small. In this overview, a major chemical group with antifungal activity, the azole derivatives, is examined. Included are historical and state of the art information on the in vitro activity, experimental in vivo activity, mode of action, pharmacokinetics, clinical studies, and uses and adverse reactions of imidazoles currently marketed (clotrimazole, miconazole, econazole, ketoconazole, bifonazole, butoconazole, croconazole, fenticonazole, isoconazole, oxiconazole, sulconazole, and tioconazole) and under development (aliconazole and omoconazole), as well as triazoles currently marketed (terconazole) and under development (fluconazole, itraconazole, vibunazole, alteconazole, and ICI 195,739). PMID:3069196

  12. Antifungal activity of fruit pulp extract from Bromelia pinguin.

    PubMed

    Camacho-Hernández, I L; Chávez-Velázquez, J A; Uribe-Beltrán, M J; Ríos-Morgan, A; Delgado-Vargas, F

    2002-08-01

    The methanol extract of the fruit pulp of Bromelia pinguin was evaluated for its antifungal activity. The extract showed a significant activity against some Trichophyton strains, although Candida strains were generally insensitive.

  13. Solubility, photostability and antifungal activity of phenylpropanoids encapsulated in cyclodextrins.

    PubMed

    Kfoury, Miriana; Lounès-Hadj Sahraoui, Anissa; Bourdon, Natacha; Laruelle, Frédéric; Fontaine, Joël; Auezova, Lizette; Greige-Gerges, Hélène; Fourmentin, Sophie

    2016-04-01

    Effects of the encapsulation in cyclodextrins (CDs) on the solubility, photostability and antifungal activities of some phenylpropanoids (PPs) were investigated. Solubility experiments were carried out to evaluate the effect of CDs on PPs aqueous solubility. Loading capacities and encapsulation efficiencies of freeze-dried inclusion complexes were determined. Moreover, photostability assays for both inclusion complexes in solution and solid state were performed. Finally, two of the most widespread phytopathogenic fungi, Fusarium oxysporum and Botrytis cinerea, were chosen to examine the antifungal activity of free and encapsulated PPs. Results showed that encapsulation in CDs significantly increased the solubility and photostability of studied PPs (by 2 to 17-fold and 2 to 44-fold, respectively). Free PPs revealed remarkable antifungal properties with isoeugenol showing the lowest half-maximal inhibitory concentration (IC50) values of mycelium growth and spore germination inhibition. Encapsulated PPs, despite their reduced antifungal activity, could be helpful to solve drawbacks such as solubility and stability.

  14. Research to Identify Effective Antifungal Agents, 1991 Annual Report.

    SciTech Connect

    Schreck, Carl

    1991-09-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990). The objectives of the present study was to evaluate up to 10 candidate fungicides.

  15. Cryptic antifungal compounds active by synergism with polyene antibiotics.

    PubMed

    Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya

    2016-04-01

    The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity.

  16. Research to Identify Effective Antifungal Agents, 1993 Annual Report.

    SciTech Connect

    Schreck, Carl

    1993-10-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990, 1991, and 1992). The objectives of the present study were to select and evaluate candidate fungicides.

  17. Antifungal effect of (+)-pinoresinol isolated from Sambucus williamsii.

    PubMed

    Hwang, Bomi; Lee, Juneyoung; Liu, Qing-He; Woo, Eun-Rhan; Lee, Dong Gun

    2010-05-14

    In this study, we investigated the antifungal activity and mechanism of action of (+)-pinoresinol, a biphenolic compound isolated from the herb Sambucus williamsii,used in traditional medicine. (+)-Pinoresinol displays potent antifungal properties without hemolytic effects on human erythrocytes. To understand the antifungal mechanism of (+)-pinoresinol, we conducted fluorescence experiments on the human pathogen Candida albicans. Fluorescence analysis using 1,6-diphenyl-1,3,5-hexatriene (DPH) indicated that the (+)-pinoresinol caused damage to the fungal plasma membrane. This result was confirmed by using rhodamine-labeled giant unilamellar vesicle (GUV) experiments. Therefore, the present study indicates that (+)-pinoresinol possesses fungicidal activities and therapeutic potential as an antifungal agent for the treatment of fungal infectious diseases in humans.

  18. Antifungal activity of Bacillus sp. isolated from compost.

    PubMed

    Czaczyk, K; Stachowiak, B; Trojanowska, K; Gulewicz, K

    2000-01-01

    Four strains of Bacillus isolated from lupine compost exhibited an antifungal activity against six plant fungal pathogens (Rhizoctonia solani, Bipolaris sorokiniana, Sclerotinia sclerotiorum, Trichothecium roseum, Fusarium solani, Fusarium oxysporum). It was significantly influenced by the composition of the cultivation media.

  19. In Vitro Antifungal Susceptibilities of Five Species of Sporothrix▿

    PubMed Central

    Marimon, Rita; Serena, Carolina; Gené, Josepa; Cano, Josep; Guarro, Josep

    2008-01-01

    Ninety-two isolates belonging to five species of the Sporothrix schenckii complex were tested in vitro against 12 antifungal agents, using a reference microdilution method. There were significant differences among the species; Sporothrix brasiliensis was the species that showed the best response to antifungals, and S. mexicana had the worst response. In general, terbinafine was the most active drug, followed by ketoconazole and posaconazole. PMID:18039919

  20. Chemosensitization as a Means to Augment Commercial Antifungal Agents

    PubMed Central

    Campbell, Bruce C.; Chan, Kathleen L.; Kim, Jong H.

    2012-01-01

    Antimycotic chemosensitization and its mode of action are of growing interest. Currently, use of antifungal agents in agriculture and medicine has a number of obstacles. Foremost of these is development of resistance or cross-resistance to one or more antifungal agents. The generally high expense and negative impact, or side effects, associated with antifungal agents are two further issues of concern. Collectively, these problems are exacerbated by efforts to control resistant strains, which can evolve into a treadmill of higher dosages for longer periods. This cycle in turn, inflates cost of treatment, dramatically. A further problem is stagnation in development of new and effective antifungal agents, especially for treatment of human mycoses. Efforts to overcome some of these issues have involved using combinations of available antimycotics (e.g., combination therapy for invasive mycoses). However, this approach has had inconsistent success and is often associated with a marked increase in negative side effects. Chemosensitization by natural compounds to increase effectiveness of commercial antimycotics is a somewhat new approach to dealing with the aforementioned problems. The potential for safe natural products to improve antifungal activity has been observed for over three decades. Chemosensitizing agents possess antifungal activity, but at insufficient levels to serve as antimycotics, alone. Their main function is to disrupt fungal stress response, destabilize the structural integrity of cellular and vacuolar membranes or stimulate production of reactive oxygen species, augmenting oxidative stress and apoptosis. Use of safe chemosensitizing agents has potential benefit to both agriculture and medicine. When co-applied with a commercial antifungal agent, an additive or synergistic interaction may occur, augmenting antifungal efficacy. This augmentation, in turn, lowers effective dosages, costs, negative side effects and, in some cases, countermands resistance

  1. Potent heterologous antifungal proteins from cheeseweed (Malva parviflora).

    PubMed

    Wang, X; Bunkers, G J

    2000-12-20

    Two novel antifungal proteins were purified and characterized from cheeseweed (Malva parviflora). Both proteins, designated CW-1 and CW-2, are composed of two different subunits of 5000 and 3000 Da, respectively. These proteins possess very potent antifungal activities, and more interestingly the inhibition is fungicidal instead of fungistatic. At low salt condition, the IC(50) of CW-1 and CW-2 against Fusarium graminearum (Fg) is 2.5 ppm. At high salt condition which diminishes the antifungal activity of many antifungal proteins, both CW-1 and CW-2 still maintain potent activity against Fg with IC(50) of 10 ppm. The two subunits could be separated by gel filtration in the presence of 6 M urea, but their antifungal activity cannot be recovered after the removal of urea. Amino acid sequence analysis indicates that both subunits of CW-1 show homology to 2S albumin, whereas the two subunits of CW-2 have homology to vicilin protein from cotton. To our knowledge, this is the first report of isolation and characterization of heterologous antifungal proteins from any source.

  2. Oral fungi in HIV: challenges in antifungal therapies.

    PubMed

    Nittayananta, W

    2016-04-01

    Oral candidiasis (OC) caused by Candida species is a common fungal infection among HIV-infected individuals. Despite the wide use of antiretroviral therapy (ART) resulting in a declined prevalence, OC remains the most common oral lesions seen in those living with HIV/AIDS. Various topical and systemic antifungal drugs are available to treat OC. However, due to the patients' immunodeficiency and the nature of OC as biofilm-associated infection, relapse is frequently observed after cessation of antifungal therapy. In addition, long-term antifungal therapy may lead to drug resistance. This review article addressed three major challenges in the treatment of OC in HIV infection including antifungal drug resistance, biofilm-associated infection of OC, and the host underlying immunodeficiency. To reduce the risks of antifungal drug resistance, the author recommends that future studies should focus on herbal plant-derived compounds with antifungal activity that may be used in combination with the drugs. Also, it is recommended that more research should be carried out to explore how to enhance the host innate immunity against oral Candida. PMID:27109279

  3. Antifungal effect and mechanism of garlic oil on Penicillium funiculosum.

    PubMed

    Li, Wen-Ru; Shi, Qing-Shan; Liang, Qing; Huang, Xiao-Mo; Chen, Yi-Ben

    2014-10-01

    Garlic oil is a kind of fungicide, but little is known about its antifungal effects and mechanism. In this study, the chemical constituents, antifungal activity, and effects of garlic oil were studied with Penicillium funiculosum as a model strain. Results showed that the minimum fungicidal concentrations (MFCs, v/v) were 0.125 and 0.0313 % in agar medium and broth medium, respectively, suggesting that the garlic oil had a strong antifungal activity. The main ingredients of garlic oil were identified as sulfides, mainly including disulfides (36 %), trisulfides (32 %) and monosulfides (29 %) by gas chromatograph-mass spectrometer (GC/MS), which were estimated as the dominant antifungal factors. The observation results by transmission electron microscope (TEM) and scanning electron microscope (SEM) indicated that garlic oil could firstly penetrate into hyphae cells and even their organelles, and then destroy the cellular structure, finally leading to the leakage of both cytoplasm and macromolecules. Further proteomic analysis displayed garlic oil was able to induce a stimulated or weakened expression of some key proteins for physiological metabolism. Therefore, our study proved that garlic oil can work multiple sites of the hyphae of P. funiculosum to cause their death. The high antifungal effects of garlic oil makes it a broad application prospect in antifungal industries.

  4. Synthesis and antifungal activity of benzimidazole, benzotriazole and aminothiazole derivatives

    PubMed Central

    Khabnadideh, S.; Rezaei, Z.; Pakshir, K.; Zomorodian, K.; Ghafari, N.

    2012-01-01

    In recent years, the use of antifungal drugs in human medicine has increased, especially with the advent of AIDS epidemic. Efforts have focused on the development of new, less toxic and more efficacious antifungal drugs with novel mechanism of action. The purpose of this study was to synthesize of some new benzimidazole, benzotriazole and aminothiazole derivatives and to evaluate their activity against some species of Candida, Aspergillus and dermatophytes. The desired compounds were synthesized by the reaction of benzimidazole and benzotriazole with bromoalkanes and also by the reaction of an amide derivative of aminothiazole with 2-piperazino-1-ethanol in an efficient solvent in the presence of tetraethyl ammounim bromide or triethylamine) as catalyst. Chemical structures of all the new compounds were confirmed by spectrophotometric methods. Antifungal activities of the new compounds were evaluated by broth micro dilution method as recommended by CLSI. Among the tested compounds, 1-nonyl-1H-benzo[d]imidazole and 1-decyl-1H-benzo[d]imidazole exhibited the best antifungal activities. Of the examined synthetic compounds in different categories, benzimidazole derivatives established better antifungal activities than benzotriazole derivatives, and the piperazine analogue had no significant antifungal effect. PMID:23181082

  5. Potentiation of antifungal effect of a mixture of two antifungal fractions obtained from Baccharis glutinosa and Jacquinia macrocarpa plants.

    PubMed

    Medina-López, Carlos F; Plascencia-Jatomea, Maribel; Cinco-Moroyoqui, Francisco J; Yépiz-Gómez, María S; Cortez-Rocha, Mario O; Rosas-Burgos, Ema C

    2016-11-01

    The aim of the present work was to evaluate the effect of mixtures of antifungal fractions extracted from Baccharis glutinosa and Jacquinia macrocarpa plants on the development of the filamentous fungi Aspergillus flavus and Fusarium verticillioides. The minimal inhibitory concentration that inhibited 50% of growth (MIC50) of each plant antifungal fraction was determined from the percentage radial growth inhibition of both fungi. Binomial mixtures made with both plant fractions were used at their MIC50 to determine the Fractional Inhibitory Concentration index (FIC index) for each fungus in order to evaluate their synergistic effect. Each synergistic mixture was analyzed in their effect on spore germination, spore size, spore viability, mitotic divisions, hyphal diameter and length, and number of septa per hypha. Some antifungal mixtures, even at low concentrations, showed higher antifungal effect than those of the individual antifungal fraction. The FIC indices of mixtures that showed the highest antifungal activity against A. flavus and F. verticillioides were 0.5272 and 0.4577, respectively, indicating a synergistic effect against both fungi. Only 12% and 8% of the spores of A. flavus and F. verticillioides, respectively, treated with the synergistic mixtures, were able to germinate, although their viability was not affected. An increase in the number of septa per hypha of both fungi was observed. The results indicated that the synergistic mixtures strongly affected the fungal growth even at lower concentrations than those of the individual plant fractions. PMID:27382921

  6. Nationwide study of candidemia, antifungal use, and antifungal drug resistance in Iceland, 2000 to 2011.

    PubMed

    Asmundsdottir, Lena Ros; Erlendsdottir, Helga; Gottfredsson, Magnus

    2013-03-01

    Candidemia is often a life-threatening infection, with highly variable incidence among countries. We conducted a nationwide study of candidemia in Iceland from 2000 to 2011, in order to determine recent trends in incidence rates, fungal species distribution, antifungal susceptibility patterns, and concurrent antifungal consumption. A total of 208 infection episodes in 199 patients were identified. The average incidence during the 12 years was 5.7 cases/100,000 population/year, which was significantly higher than that from 1990 to 1999 (4.3/100,000/year; P = 0.02). A significant reduction in the use of blood cultures was noted in the last 3 years of the study, coinciding with the economic crisis in the country (P < 0.001). Age-specific incidence rates were highest among patients at the extremes of age, 20.7/100,000 for <1 year of age and 18.1/100,000 for >60 years, and varied by gender. Age-specific incidence among males >80 years old was 28.6/100,000/year, and it was 8.3/100,000/year for females in this age group (P = 0.028). The 30-day survival rate among adult patients remained unchanged compared to that from 1990 to 1999 (70.4% versus 69.5%, P = 0.97). Candida albicans was the predominant species (56%), followed by C. glabrata (16%) and C. tropicalis (13%). The species distribution remained stable compared to that from previous decades. Fluconazole use increased 2.4-fold from 2000 to 2011, with no increase in resistance. In summary, the incidence of candidemia in Iceland has continued to increase but may have reached a steady state, and no increase in antifungal drug resistance has been noted. Decreased use of blood cultures toward the end of the study may have influenced detection rates.

  7. Nationwide Study of Candidemia, Antifungal Use, and Antifungal Drug Resistance in Iceland, 2000 to 2011

    PubMed Central

    Asmundsdottir, Lena Ros; Erlendsdottir, Helga

    2013-01-01

    Candidemia is often a life-threatening infection, with highly variable incidence among countries. We conducted a nationwide study of candidemia in Iceland from 2000 to 2011, in order to determine recent trends in incidence rates, fungal species distribution, antifungal susceptibility patterns, and concurrent antifungal consumption. A total of 208 infection episodes in 199 patients were identified. The average incidence during the 12 years was 5.7 cases/100,000 population/year, which was significantly higher than that from 1990 to 1999 (4.3/100,000/year; P = 0.02). A significant reduction in the use of blood cultures was noted in the last 3 years of the study, coinciding with the economic crisis in the country (P < 0.001). Age-specific incidence rates were highest among patients at the extremes of age, 20.7/100,000 for <1 year of age and 18.1/100,000 for >60 years, and varied by gender. Age-specific incidence among males >80 years old was 28.6/100,000/year, and it was 8.3/100,000/year for females in this age group (P = 0.028). The 30-day survival rate among adult patients remained unchanged compared to that from 1990 to 1999 (70.4% versus 69.5%, P = 0.97). Candida albicans was the predominant species (56%), followed by C. glabrata (16%) and C. tropicalis (13%). The species distribution remained stable compared to that from previous decades. Fluconazole use increased 2.4-fold from 2000 to 2011, with no increase in resistance. In summary, the incidence of candidemia in Iceland has continued to increase but may have reached a steady state, and no increase in antifungal drug resistance has been noted. Decreased use of blood cultures toward the end of the study may have influenced detection rates. PMID:23269738

  8. Antifungal agents, Part 11. Biphenyl analogues of naftifine: synthesis and antifungal activities.

    PubMed

    Porretta, G C; Fioravanti, R; Biava, M; Artico, M; Villa, A; Simonetti, N

    1995-09-01

    A series of naftifine analogues having the biphenyl instead of the naphthyl moiety have been synthesized in a search devoted to study bioanalogues of clinically efficacious antifungal agents. The new derivatives were tested against Candida albicans by the direct contact method. They were also assayed against Gram-positive and Gram-negative bacteria and against some isolates of plant pathogenic fungi. Derivatives 8a, 8c, and 9a were found to be active against Candida albicans, derivative 5a was active against E. coli, a very resistant species to antimycotic agents, and derivatives 8a and 8b inhibited the plant pathogenic Rhizoctonia solani.

  9. Antifungal and molluscicidal saponins from Serjania salzmanniana.

    PubMed

    Ekabo, O A; Farnsworth, N R; Henderson, T O; Mao, G; Mukherjee, R

    1996-04-01

    An investigation of Serjania salzmanniana for biologically active substances has led to the isolation of two novel saponins, salzmannianoside A (3-O-[[beta-D- glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl] gypsogenin) [3] and salzmannianoside B (3-O-[[beta-D-glucopyranosyl-(1-->4)]-[alpha-L- arabinopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)] -alpha-L-arabinopyranosyl] hederagenin) (4). Two known saponins, pulsatilla saponin D (3-O-[[beta-D- glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl] hederagenin) (1) and 3-O-[[beta-D-glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-a lpha-L- arabinopyranosyl] oleanolic acid (2) were also isolated from this plant. The structures of 3 and 4 were elucidated by FABMS and 2D NMR techniques. All these four saponins were mollusicidal, causing 70-100% mortality at 10 ppm against Biomphalaria alexandrina, a vector of Schistosoma mansoni in the Nile Valley. The saponins also showed antifungal activity against Cryptococcus neoformans and Candida albicans at minimal inhibitory concentrations of 8 and 16 micrograms/mL, respectively.

  10. Antifungal and antibacterial activity of marine microorganisms.

    PubMed

    El Amraoui, B; El Amraoui, M; Cohen, N; Fassouane, A

    2014-03-01

    In order to explore marine microorganisms with pharmaceutical potential, marine bacteria, collected from different coastal areas of the Moroccan Atlantic Ocean, were previously isolated from seawater, sediment, marine invertebrates and seaweeds. The antimicrobial activities of these microorganisms were investigated against the pathogens involved in human pathologies. Whole cultures of 34 marine microorganisms were screened for antimicrobial activities using the method of agar diffusion against three Gram-positive bacteria, two Gram-negative bacteria, and against yeast. The results showed that among the 34 isolates studied, 28 (82%) strains have antimicrobial activity against at least one pathogen studied, 11 (32%) strains have antifungal activity and 24 (76%) strains are active against Gram-positive bacteria, while 21 (62%) strains are active against Gram-negative bacteria. Among isolates having antimicrobial activity, 14 were identified and were assigned to the genera Acinetobacter, Aeromonas, Alcaligenes, Bacillus, Chromobacterium, Enterococcus, Pantoea and Pseudomonas. Due to a competitive role for space and nutrient, the marine microorganisms can produce antibiotic substance; therefore, these marine microorganisms were expected to be potential resources of natural antibiotic products.

  11. Macrocyclic trichothecenes as antifungal and anticancer compounds.

    PubMed

    de Carvalho, Maira Peres; Weich, Herbert; Abraham, Wolf-Rainer

    2016-01-01

    Trichothecenes are sesquiterpenoid metabolites produced by fungi and species of the plant genus Baccharis, family Asteraceae. They comprise a tricyclic core with an epoxide at C-12 and C-13 and can be grouped into non-macrocyclic and macrocyclic compounds. While many of these compounds are of concern in agriculture, the macrocyclic metabolites have been evaluated as antiviral, anti-cancer, antimalarial and antifungal compounds. Some known cytotoxic responses on eukaryotic cells include inhibition of protein, DNA and RNA syntheses, interference with mitochondrial function, effects on cell division and membranes. These targets however have been elucidated essentially employing non-macrocyclic trichothecenes and only one or two closely related macrocyclic compounds. For several macrocyclic trichothecenes high selectivity against fungal species and against cancer cell lines have been reported suggesting that the macrocycle and its stereochemistry are of crucial importance regarding biological activity and selectivity. This review is focused on compounds belonging to the macrocyclic type, where a cyclic diester or triester ring binds to the trichothecane moiety at C-4 and C- 15 leading to natural products belonging to the groups of satratoxins, verrucarins, roridins, myrotoxins and baccharinoids. Their biological activities, cytotoxic mechanisms and structure-activity relationships (SAR) are discussed. From the reported data it becomes evident that even small changes in the molecules can lead to pronounced effects on biological activity or selectivity against cancer cells lines. Understanding the underlying mechanisms may help to design highly specific drugs for cancer therapy.

  12. Antifungal innate immunity: recognition and inflammatory networks.

    PubMed

    Becker, Katharina L; Ifrim, Daniela C; Quintin, Jessica; Netea, Mihai G; van de Veerdonk, Frank L

    2015-03-01

    A large variety of fungi are present in the environment, among which a proportion colonizes the human body, usually without causing any harm. However, depending on the host immune status, commensals can become opportunistic pathogens that induce diseases ranging from superficial non-harmful infection to life-threatening systemic disease. The interplay between the host and the fungal commensal flora is being orchestrated by an efficient recognition of the microorganisms, which in turn ensures a proper balance between tolerance of the normal fungal flora and induction of immune defense mechanisms when invasion occurs. Pattern recognition receptors (PRRs) play a significant role in maintaining this balance due to their capacity to sense fungi and induce host responses such as the induction of proinflammatory cytokines involved in the activation of innate and adaptive immune responses. In the present review, we will discuss the most recent findings regarding the recognition of Candida albicans and Aspergillus fumigatus and the different types of immune cells that play a role in antifungal host defense. PMID:25527294

  13. Potato Dextrose Agar Antifungal Susceptibility Testing for Yeasts and Molds: Evaluation of Phosphate Effect on Antifungal Activity of CMT-3

    PubMed Central

    Liu, Yu; Tortora, George; Ryan, Maria E.; Lee, Hsi-Ming; Golub, Lorne M.

    2002-01-01

    The broth macrodilution method (BMM) for antifungal susceptibility testing, approved by the National Committee for Clinical Laboratory Standards (NCCLS), was found to have deficiencies in testing of the antifungal activity of a new type of antifungal agent, a nonantibacterial chemically modified tetracycline (CMT-3). The high content of phosphate in the medium was found to greatly increase the MICs of CMT-3. To avoid the interference of phosphate in the test, a new method using potato dextrose agar (PDA) as a culture medium was developed. Eight strains of fungi, including five American Type Culture Collection strains and three clinical isolates, were used to determine the MICs of amphotericin B and itraconazole with both the BMM and the PDA methods. The MICs of the two antifungal agents determined with the PDA method showed 99% agreement with those determined with the BMM method within 1 log2 dilution. Similarly, the overall reproducibility of the MICs with the PDA method was above 97%. Three other antifungal agents, fluconazole, ketoconazole, and CMT-3, were also tested in parallel against yeasts and molds with both the BMM and the PDA methods. The MICs of fluconazole and ketoconazole determined with the PDA method showed 100% agreement within 1 log2 dilution of those obtained with the BMM method. However, the MICs of CMT-3 determined with the BMM method were as high as 128 times those determined with the PDA method. The effect of phosphate on the antifungal activity of CMT-3 was evaluated by adding Na2HPO4 to PDA in the new method. It was found that the MIC of CMT-3 against a Penicillium sp. increased from 0.5 μg/ml (control) to 2.0 μg/ml when the added phosphate was used at a concentration of 0.8 mg/ml, indicating a strong interference of Na2HPO4 with the antifungal activity of CMT-3. Except for fluconazole, all the other antifungal agents demonstrated clear end points among the yeasts and molds tested. Nevertheless, with its high reproducibility, good

  14. Antifungal hydroxy fatty acids produced during sourdough fermentation: microbial and enzymatic pathways, and antifungal activity in bread.

    PubMed

    Black, Brenna A; Zannini, Emanuele; Curtis, Jonathan M; Gänzle, Michael G

    2013-03-01

    Lactobacilli convert linoleic acid to hydroxy fatty acids; however, this conversion has not been demonstrated in food fermentations and it remains unknown whether hydroxy fatty acids produced by lactobacilli have antifungal activity. This study aimed to determine whether lactobacilli convert linoleic acid to metabolites with antifungal activity and to assess whether this conversion can be employed to delay fungal growth on bread. Aqueous and organic extracts from seven strains of lactobacilli grown in modified De Man Rogosa Sharpe medium or sourdough were assayed for antifungal activity. Lactobacillus hammesii exhibited increased antifungal activity upon the addition of linoleic acid as a substrate. Bioassay-guided fractionation attributed the antifungal activity of L. hammesii to a monohydroxy C(18:1) fatty acid. Comparison of its antifungal activity to those of other hydroxy fatty acids revealed that the monohydroxy fraction from L. hammesii and coriolic (13-hydroxy-9,11-octadecadienoic) acid were the most active, with MICs of 0.1 to 0.7 g liter(-1). Ricinoleic (12-hydroxy-9-octadecenoic) acid was active at a MIC of 2.4 g liter(-1). L. hammesii accumulated the monohydroxy C(18:1) fatty acid in sourdough to a concentration of 0.73 ± 0.03 g liter(-1) (mean ± standard deviation). Generation of hydroxy fatty acids in sourdough also occurred through enzymatic oxidation of linoleic acid to coriolic acid. The use of 20% sourdough fermented with L. hammesii or the use of 0.15% coriolic acid in bread making increased the mold-free shelf life by 2 to 3 days or from 2 to more than 6 days, respectively. In conclusion, L. hammesii converts linoleic acid in sourdough and the resulting monohydroxy octadecenoic acid exerts antifungal activity in bread.

  15. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis.

    PubMed

    Tabata, Yuji; Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2016-02-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. PMID:26643333

  16. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis

    PubMed Central

    Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2015-01-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. PMID:26643333

  17. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis.

    PubMed

    Tabata, Yuji; Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2016-02-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation.

  18. Antifungal susceptibilities of Candida species isolated from urine culture.

    PubMed

    Toka Özer, Türkan; Durmaz, Süleyman; Yula, Erkan

    2016-09-01

    Candida spp. are the most common opportunistic mycosis worldwide. Although Candida albicans is the most common cause of urinary tract infections, the frequency of non-albicans Candida species is increasing with common use of antifungal in the prophylaxis and treatment. This may lead to difficulties in treatment. Antifungal tests should be applied with identification of species for effective treatment. In this study, identification of Candida species isolated from urine culture and investigation of susceptibility of these strains to amphotericin B, flucytosine, fluconazole, voriconazole was aimed. In this study, 58 Candida strains isolated from urine cultures at Osmaniye State Hospital between January 2012 and April 2013 were included. Urine culture and antifungal susceptibility tests were applied. Incidence rate of Candida spp. was determined as C. albicans (56.9%), Candida glabrata (20.6%), Candida tropicalis (10.3%), Candida parapsilosis (7%), Candida krusei (3.4%), Candida kefyr (1.8%). Most of the isolates were susceptible to amphotericin B, flucytosine, fluconazole, voriconazole. Twenty three (39.7%) Candida strains were isolated from internal medical branches and Intensive Care Unit and 12 (20.6%) from the Surgical Medical Branches. C. albicans and C. glabrata species were isolated most frequently as a candiduria factor in this hospital between January 2012 and April 2013. The analysis of antifungal susceptibility profile shows no significant resistance to antifungals.

  19. Chloroquine sensitizes biofilms of Candida albicans to antifungal azoles.

    PubMed

    Shinde, Ravikumar Bapurao; Raut, Jayant Shankar; Chauhan, Nitin Mahendra; Karuppayil, Sankunny Mohan

    2013-01-01

    Biofilms formed by Candida albicans, a human pathogen, are known to be resistant to different antifungal agents. Novel strategies to combat the biofilm associated Candida infections like multiple drug therapy are being explored. In this study, potential of chloroquine to be a partner drug in combination with four antifungal agents, namely fluconazole, voriconazole, amphotericin B, and caspofungin, was explored against biofilms of C. albicans. Activity of various concentrations of chloroquine in combination with a particular antifungal drug was analyzed in a checkerboard format. Growth of biofilm in presence of drugs was analyzed by XTT-assay, in terms of relative metabolic activity compared to that of drug free control. Results obtained by XTT-metabolic assay were confirmed by scanning electron microscopy. The interactions between chloroquine and four antifungal drugs were determined by calculating fractional inhibitory concentration indices. Azole resistance in biofilms was reverted significantly (p<0.05) in presence of 250μg/mL of chloroquine, which resulted in inhibition of biofilms at very low concentrations of antifungal drugs. No significant alteration in the sensitivity of biofilms to caspofungin and amphotericin B was evident in combination with chloroquine. This study for the first time indicates that chloroquine potentiates anti-biofilm activity of fluconazole and voriconazole. PMID:23602464

  20. Antifungal activity of essential oils against selected terverticillate penicillia.

    PubMed

    Felšöciová, Soňa; Kačániová, Miroslava; Horská, Elena; Vukovič, Nenad; Hleba, Lukáš; Petrová, Jana; Rovná, Katarina; Stričík, Michal; Hajduová, Zuzana

    2015-01-01

    The aim of this study was to screen 15 essential oils of selected plant species, viz. Lavandula angustifolia, Carum carvi, Pinus mungo var. pulmilio, Mentha piperita, Chamomilla recutita L., Pinus sylvestris, Satureia hortensis L., Origanum vulgare L., Pimpinella anisum, Rosmarinus officinalis L., Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Thymus vulgaris L., Origanum vulgare L. for antifungal activity against five Penicillium species: Penicillium brevicompactum, Penicillium citrinum, Penicillium crustosum, Penicillium expansum and Penicillium griseofulvum. The method used for screening included the disc diffusion method. The study points out the wide spectrum of antifungal activity of essential oils against Penicillium fungi. There were five essential oils of the 15 mentioned above which showed a hopeful antifungal activity: Pimpinella anisum, Chamomilla recutita L., Thymus vulgaris, Origanum vulgare L. The most hopeful antifungal activity and killing effect against all tested penicillia was found to be Origanum vulgare L. and Pimpinella anisum. The lowest level of antifungal activity was demonstrated by the oils Pinus mungo var. pulmilio, Salvia officinalis L., Abietis albia etheroleum, Chamomilla recutita L. Rausch, Rosmarinus officinalis. PMID:25780826

  1. Exploring the molecular basis of antifungal synergies using genome-wide approaches

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This is a review article summarizing genomic profiling strategies for determining the mechanism of action of antifungal synergies, and highlighting the potential applications of these technologies. Given the limitations of currently available antifungal agents and the development of drug resistance...

  2. Antifungal activity of alkyl gallates against plant pathogenic fungi.

    PubMed

    Ito, Shinsaku; Nakagawa, Yasutaka; Yazawa, Satoru; Sasaki, Yasuyuki; Yajima, Shunsuke

    2014-04-01

    The antifungal activity of alkyl gallates against plant pathogenic fungi was evaluated. All of the fungi tested in this study were susceptible to some alkyl gallates, and the effect of linear alkyl gallates against plant pathogenic fungi was similar to the previously reported effects against Gram-negative and Gram-positive bacteria. We found that branched alkyl gallates showed stronger activity than did linear alkyl gallates with similar logP values. In addition, the antifungal activity of alkyl gallates was correlated with gallate-induced inhibition of the activity of mitochondrial complex II. The antifungal activity of alkyl gallates likely originates, at least in part, from their ability to inhibit the membrane respiratory chain.

  3. Comparison of antifungal activities of Vietnamese citrus essential oils.

    PubMed

    Van Hung, Pham; Chi, Pham Thi Lan; Phi, Nguyen Thi Lan

    2013-03-01

    Citrus essential oils (EOs) are volatile compounds from citrus peels and widely used in perfumes, cosmetics, soaps and aromatherapy. In this study, inhibition of citrus EOs extracted from Vietnamese orange (Citrus sinensis), mandarin (Citrus reticulata Blanco), pomelo (Citrus grandis Osbeck) and lime (Citrus aurantifolia Swingle) on the growth of plant pathogenic fungi, Mucor hiemalis, Penicillium expansum and Fusarium proliferatum was investigated. The EOs of the citrus peels were obtained by cold-pressing method and the antifungal activity of EOs was evaluated using the agar dilution method. The results show that the EOs had significant antifungal activity. Lime EO was the best inhibitor of M. hiemalis and F. proliferatum while pomelo EO was the most effective against P. expansum. These results indicate that citrus EOs can be used as antifungal natural products in the food, pharmaceutical and cosmetic industries.

  4. Antifungal Effect of Chitosan as Ca2+ Channel Blocker

    PubMed Central

    Lee, Choon Geun; Koo, Ja Choon; Park, Jae Kweon

    2016-01-01

    The aim of this study was to investigate antifungal activity of a range of different molecular weight (MW) chitosan against Penicillium italicum. Our results demonstrate that the antifungal activity was dependent both the MW and concentration of the chitosan. Among a series of chitosan derived from the hydrolysis of high MW chitosan, the fractions containing various sizes of chitosan ranging from 3 to 15 glucosamine units named as chitooligomers-F2 (CO-F2) was found to show the highest antifungal activity against P. italicum. Furthermore, the effect of CO-F2 toward this fungus was significantly reduced in the presence of Ca2+, whereas its effect was recovered by ethylenediaminetetraacetic acid, suggesting that the CO-F2 acts via disruption of Ca2+ gradient required for survival of the fungus. Our results suggest that CO-F2 may serve as potential compounds to develop alternatives to synthetic fungicides for the control of the postharvest diseases. PMID:27298599

  5. Peptide-based Antifungal Therapies against Emerging Infections

    PubMed Central

    Matejuk, A.; Leng, Q.; Begum, M.D.; Woodle, M.C.; Scaria, P.; Chou, S-T; Mixson, A.J.

    2010-01-01

    Acquired drug resistance to mycotic infections is rapidly emerging as a major medical problem. Opportunistic fungal infections create therapeutic challenges, particularly in high risk immunocompromised patients with AIDS, cancer, and those undergoing transplantation. Higher mortality and/or morbidity rates due to invasive mycosis have been increasing over the last 20 years, and in light of growing resistance to commonly used antibiotics, novel antifungal drugs and approaches are required. Currently there is considerable interest in antifungal peptides that are ubiquitous in plant and animal kingdoms. These small cationic peptides may have specific targets or may be multifunctional in their mechanism of action. On the basis of recent advances in protein engineering and solid phase syntheses, the utility and potential of selected peptides as efficient antifungal drugs with acceptable toxicity profiles are being realized. This review will discuss recent advances in peptide therapy for opportunistic fungal infections. PMID:20495663

  6. Solid lipid nanoparticles for antifungal drugs delivery for topical applications.

    PubMed

    Trombino, Sonia; Mellace, Silvia; Cassano, Roberta

    2016-09-01

    Systemic and local infections caused by fungi, in particular those concerning the skin and nails, are increasing. Various drugs are used for mycoses treatment such as amphotericin B, nystatin and ketoconazole, fluconazole, itraconazole and fluconazole, among others. Unfortunately, many of these antifungal agents can cause side effects such as allergic and severe skin reaction. With the aim to reduce these side effects and maximize the antifungal drug activity, various drug-delivery systems have been formulated and been investigated in the last few years. In this context, solid lipid nanoparticles are attracting great attention. The aim of this review is to highlight the role of solid lipid nanoparticles as carriers of antifungal drugs for topical applications. PMID:27582235

  7. Antifungal drug resistance among Candida species: mechanisms and clinical impact.

    PubMed

    Sanguinetti, Maurizio; Posteraro, Brunella; Lass-Flörl, Cornelia

    2015-06-01

    The epidemiology of Candida infections has changed in recent years. Although Candida albicans is still the main cause of invasive candidiasis in most clinical settings, a substantial proportion of patients is now infected with non-albicans Candida species. The various Candida species vary in their susceptibility to the most commonly used antifungal agents, and the intrinsic resistance to antifungal therapy seen in some species, along with the development of acquired resistance during treatment in others, is becoming a major problem in the management of Candida infection. A better understanding of the mechanisms and clinical impact of antifungal drug resistance is essential for the efficient treatment of patients with Candida infection and for improving treatment outcomes. Herein, we report resistance to the azoles and echinocandins among Candida species.

  8. Targeting efflux pumps to overcome antifungal drug resistance.

    PubMed

    Holmes, Ann R; Cardno, Tony S; Strouse, J Jacob; Ivnitski-Steele, Irena; Keniya, Mikhail V; Lackovic, Kurt; Monk, Brian C; Sklar, Larry A; Cannon, Richard D

    2016-08-01

    Resistance to antifungal drugs is an increasingly significant clinical problem. The most common antifungal resistance encountered is efflux pump-mediated resistance of Candida species to azole drugs. One approach to overcome this resistance is to inhibit the pumps and chemosensitize resistant strains to azole drugs. Drug discovery targeting fungal efflux pumps could thus result in the development of azole-enhancing combination therapy. Heterologous expression of fungal efflux pumps in Saccharomyces cerevisiae provides a versatile system for screening for pump inhibitors. Fungal efflux pumps transport a range of xenobiotics including fluorescent compounds. This enables the use of fluorescence-based detection, as well as growth inhibition assays, in screens to discover compounds targeting efflux-mediated antifungal drug resistance. A variety of medium- and high-throughput screens have been used to identify a number of chemical entities that inhibit fungal efflux pumps. PMID:27463566

  9. Enhancement of Commercial Antifungal Agents by Kojic Acid

    PubMed Central

    Kim, Jong H.; Chang, Perng-Kuang; Chan, Kathleen L.; Faria, Natália C. G.; Mahoney, Noreen; Kim, Young K.; Martins, Maria de L.; Campbell, Bruce C.

    2012-01-01

    Natural compounds that pose no significant medical or environmental side effects are potential sources of antifungal agents, either in their nascent form or as structural backbones for more effective derivatives. Kojic acid (KA) is one such compound. It is a natural by-product of fungal fermentation commonly employed by food and cosmetic industries. We show that KA greatly lowers minimum inhibitory (MIC) or fungicidal (MFC) concentrations of commercial medicinal and agricultural antifungal agents, amphotericin B (AMB) and strobilurin, respectively, against pathogenic yeasts and filamentous fungi. Assays using two mitogen-activated protein kinase (MAPK) mutants, i.e., sakAΔ, mpkCΔ, of Aspergillus fumigatus, an agent for human invasive aspergillosis, with hydrogen peroxide (H2O2) or AMB indicate such chemosensitizing activity of KA is most conceivably through disruption of fungal antioxidation systems. KA could be developed as a chemosensitizer to enhance efficacy of certain conventional antifungal drugs or fungicides. PMID:23203038

  10. Antifungal activity of Mexican oregano (Lippia berlandieri Shauer).

    PubMed

    Portillo-Ruiz, Martha Cristina; Viramontes-Ramos, Sabina; Muñoz-Castellanos, Laila Nayzzel; Gastélum-Franco, María Guadalupe; Nevárez-Moorillón, Guadalupe Virginia

    2005-12-01

    Antifungal and sensorial properties of spices have been recognized for years. The antifungal compounds are products of the plant's secondary metabolism, and the action of those compounds could be used to inhibit the growth of spoilage and pathogenic microorganisms in food. Mexican oregano (Lippia berlandieri) grows wildly in the desert zone of Mexico and is usually added to regional foods. The goal of this study was to evaluate the antifungal activity of Mexican oregano versus food-contaminant fungi. Fungi were isolated from spoiled fruit and vegetables and identified according to morphological characteristics. The antifungal activity of oregano was evaluated by radial growth measurement on potato dextrose agar added with dried oregano (0.25 to 4.0%). The essential oil antifungal activity of oregano was also evaluated by the diffusion well test. Twenty-one fungal strains were isolated, which included Penicillium, Geotrichum, Aspergillus, and Bipolaris. In seven of the 21 strains, no inhibitory effect was observed at either concentration of oregano. An increase in growth at the lower or higher concentrations of oregano, when compared to the control, was observed in two fungal strains; in 12 strains, a strong inhibitory effect of oregano was evident. The oregano essential oil was inhibitory to all fungal strains, but there were differences in the extent of the effect. Although the antifungal effect of oregano is strongly established, there was a differential effect with the fungal strains studied. Besides pathogenic fungi and bacteria, microbial spoilage flora should be considered when the addition of spices for food preservation is proposed. PMID:16355848

  11. Antifungal activities of selected aromatic plants growing wild in Greece.

    PubMed

    Soković, M; Tzakou, O; Pitarokili, D; Couladis, M

    2002-10-01

    Essential oils of Origanum onites, Satureja thymbra, Salvia fruticosa (Greek sage), and Salvia pomifera subsp. calycina plants growing wild in Greece and their components carvacrol, camphor, and 1,8-cineole, were assayed for antifungal activity against 13 fungal species. Among the fungi tested were food poisoning, plant, animals and human pathogenic species. The oils presented various degrees of inhibition against all the fungi investigated. The highest and broadest activity was shown by the carvacrol content oils (O. onites and S. thymbra), while the oil of sage was the least effective. Carvacrol exhibited the highest and 1,8-cineole the lowest level of antifungal activity among the components tested. PMID:12428445

  12. Fungal virulence genes as targets for antifungal chemotherapy.

    PubMed Central

    Perfect, J R

    1996-01-01

    Fungal virulence genes have now met the age of molecular pathogenesis. The definition of virulence genes needs to be broad so that it encompasses the focus on molecular antifungal targets and vaccine epitopes. However, in the broad but simple definition of a virulence gene, there will be many complex genetic and host interactions which investigators will need to carefully define. Nevertheless, with the increasing numbers of serious fungal infections produced by old and newly reported organisms, the paucity of present antifungal drugs, and the likelihood of increasing drug resistance, the need for investigations into understanding fungal virulence at the molecular level has never been more important. PMID:8807043

  13. BIOSYNTHESIS OF MYCOBACILLIN, A NEW ANTIFUNGAL PEPTIDE II.

    PubMed Central

    Banerjee, Arun B.; Bose, S. K.

    1964-01-01

    Banerjee, Arun B. (University of Calcutta, Calcutta, India), and S. K. Bose. Biosynthesis of mycobacillin, a new antifungal peptide. II. Relation between streptomycin dependence and biosynthesis. J. Bacteriol. 87:1402–1405. 1964.—A streptomycin-dependent variant was isolated by a single-step mutation process from a strain of Bacillus subtilis capable of producing mycobacillin, a cyclic polypeptide antifungal antibiotic. Streptomycin inhibited the growth of this variant in concentrations exceeding the optimal level. Studies on the biosynthesis of mycobacillin and protein in this variant indicate that the two processes are different and that the deprivation of streptomycin has no effect on mycobacillin synthesis. PMID:14188720

  14. Antibacterial and antifungal metal based triazole Schiff bases.

    PubMed

    Chohan, Zahid H; Hanif, Muhammad

    2013-10-01

    A new series of four biologically active triazole derived Schiff base ligands (L(1)-L(4)) and their cobalt(II), nickel(II), copper(II) and zinc(II) complexes (1-16) have been synthesized and characterized. The ligands were prepared by the condensation reaction of 3-amino-5-methylthio-1H-1,2,4-triazole with chloro-, bromo- and nitro-substituted 2-hydroxybenzaldehyde in an equimolar ratio. The antibacterial and antifungal bioactivity data showed the metal(II) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species.

  15. Antifungal activity of three mouth rinses--in vitro study.

    PubMed

    Abirami, C P; Venugopal, Pankajalakshmi V

    2005-01-01

    Mouthrinses are nowadays routinely included in the home care oral hygiene maintenance besides dentifrice/tooth paste. Mouthrinses prevent bacterial attachment and prevent or slow down bacterial proliferation. Fungal organisms have now gained more importance due to increased incidence of AIDS/HIV. This has necessitated for mouthrinses to possess antifungal activity also. The mouthrinses used were Povidone iodine ( Wokadine), Thymol with Eucalyptol and Benzoic acid (Listerine) and fluoride with Triclosan (Colgate Plax), which were tested against oral isolates of different species of Candida. The agar diffusion test was used to evaluate the inhibitory activity of the mouthrinses and all of them exhibited antifungal activity especially against Candida albicans. PMID:16758789

  16. Recent advances in topical formulation carriers of antifungal agents.

    PubMed

    Bseiso, Eman Ahmed; Nasr, Maha; Sammour, Omaima; Abd El Gawad, Nabaweya A

    2015-01-01

    Fungal infections are amongst the most commonly encountered diseases affecting the skin. Treatment approaches include both topical and oral antifungal agents. The topical route is generally preferred due to the possible side effects of oral medication. Advances in the field of formulation may soon render outdated conventional products such as creams, ointments and gels. Several carrier systems loaded with antifungal drugs have demonstrated promising results in the treatment of skin fungal infections. Examples of these newer carriers include micelles, lipidic systems such as solid lipid nanoparticles and nanostructured lipid carriers, microemulsions and vesicular systems such as liposomes, niosomes, transfersomes, ethosomes, and penetration enhancer vesicles. PMID:26261140

  17. Antifungal activity of three mouth rinses--in vitro study.

    PubMed

    Abirami, C P; Venugopal, Pankajalakshmi V

    2005-01-01

    Mouthrinses are nowadays routinely included in the home care oral hygiene maintenance besides dentifrice/tooth paste. Mouthrinses prevent bacterial attachment and prevent or slow down bacterial proliferation. Fungal organisms have now gained more importance due to increased incidence of AIDS/HIV. This has necessitated for mouthrinses to possess antifungal activity also. The mouthrinses used were Povidone iodine ( Wokadine), Thymol with Eucalyptol and Benzoic acid (Listerine) and fluoride with Triclosan (Colgate Plax), which were tested against oral isolates of different species of Candida. The agar diffusion test was used to evaluate the inhibitory activity of the mouthrinses and all of them exhibited antifungal activity especially against Candida albicans.

  18. Antifungal Drugs for Onychomycosis: Efficacy, Safety, and Mechanisms of Action.

    PubMed

    Rosen, Theodore; Stein Gold, Linda F

    2016-03-01

    In 1996, oral terbinafine joined itraconazole and fluconazole on the short list of systemic medications that could be used to treat onychomycosis (although fluconazole was not approved for this indication by the US Food and Drug Administration [FDA], it was commonly used for this purpose). In 1999, ciclopirox was the first topical treatment to be FDA approved. The addition of the topical antifungal agents efinaconazole and tavaborole in 2014 expanded the roster of medications available to more effectively manage onychomycosis in a wide range of patients, including those for whom comorbid conditions, concomitant medications, or patient preference limited the use of systemic antifungals. PMID:27074700

  19. Antifungal susceptibility profile of cryptic species of Aspergillus.

    PubMed

    Alastruey-Izquierdo, Ana; Alcazar-Fuoli, Laura; Cuenca-Estrella, Manuel

    2014-12-01

    The use of molecular tools has led to the description of new cryptic species among different Aspergillus species complexes. Their frequency in the clinical setting has been reported to be between 10 and 15%. The susceptibility to azoles and amphotericin B of many of these species is low, and some of them, such as Aspergillus calidoustus or Aspergillus lentulus, are considered multi-resistant. The changing epidemiology, the frequency of cryptic species, and the different susceptibility profiles make antifungal susceptibility testing an important tool to identify the optimal antifungal agent to treat the infections caused by these species.

  20. Impact of brief exposure to antifungal agents on the post-antifungal effect and hemolysin activity of oral Candida albicans

    PubMed Central

    ELLEPOLA, Arjuna Nishantha; KHAJAH, Rana; JAYATILAKE, Sumedha; SAMARANAYAKE, Lakshman; SHARMA, Prem; KHAN, Zia

    2015-01-01

    Post-antifungal effect (PAFE) of Candida and its production of hemolysin are determinants of candidal pathogenicity. Candida albicans is the foremost aetiological agent of oral candidosis, which can be treated with polyene, azole, and echinocandin antifungals. However, once administered, the intraoral concentrations of these drugs tend to be subtherapeutic and transient due to the diluent effect of saliva and cleansing effect of the oral musculature. Hence, intra-orally, Candida may undergo a brief exposure to antifungal drugs. Objective Therefore, the PAFE and hemolysin production of oral C. albicans isolates following brief exposure to sublethal concentrations of the foregoing antifungals were evaluated. Material and Methods A total of 50 C. albicans oral isolates obtained from smokers, diabetics, asthmatics using steroid inhalers, partial denture wearers and healthy individuals were exposed to sublethal concentrations of nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole for 60 min. Thereafter, the drugs were removed and the PAFE and hemolysin production were determined by previously described turbidometric and plate assays, respectively. Results Nystatin, amphotericin B, caspofungin and ketoconazole induced mean PAFE (hours) of 2.2, 2.18, 2.2 and 0.62, respectively. Fluconazole failed to produce a PAFE. Hemolysin production of these isolates was suppressed with a percentage reduction of 12.27, 13.47, 13.33, 8.53 and 4.93 following exposure to nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole, respectively. Conclusions Brief exposure to sublethal concentrations of antifungal drugs appears to exert an antifungal effect by interfering with the growth as well as hemolysin production of C. albicans. PMID:26398514

  1. Antifungal activities of SCY-078 (MK-3118) and standard antifungal agents against clinical non-Aspergillus mold isolates.

    PubMed

    Lamoth, Frédéric; Alexander, Barbara D

    2015-07-01

    The limited armamentarium of active and oral antifungal drugs against emerging non-Aspergillus molds is of particular concern. Current antifungal agents and the new orally available beta-1,3-d-glucan synthase inhibitor SCY-078 were tested in vitro against 135 clinical non-Aspergillus mold isolates. Akin to echinocandins, SCY-078 showed no or poor activity against Mucoromycotina and Fusarium spp. However, SCY-078 was highly active against Paecilomyces variotii and was the only compound displaying some activity against notoriously panresistant Scedosporium prolificans.

  2. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology

    PubMed Central

    Ashbee, H. Ruth; Barnes, Rosemary A.; Johnson, Elizabeth M.; Richardson, Malcolm D.; Gorton, Rebecca; Hope, William W.

    2014-01-01

    The burden of human disease related to medically important fungal pathogens is substantial. An improved understanding of antifungal pharmacology and antifungal pharmacokinetics–pharmacodynamics has resulted in therapeutic drug monitoring (TDM) becoming a valuable adjunct to the routine administration of some antifungal agents. TDM may increase the probability of a successful outcome, prevent drug-related toxicity and potentially prevent the emergence of antifungal drug resistance. Much of the evidence that supports TDM is circumstantial. This document reviews the available literature and provides a series of recommendations for TDM of antifungal agents. PMID:24379304

  3. [Recent advances in the study of antifungal lead compounds with new chemical scaffolds].

    PubMed

    Shao, Lü-cheng; Sheng, Chun-quan; Zhang, Wan-nian

    2007-11-01

    In recent years, the incidence of infections caused by invasive fungal pathogens has increased dramatically. However, most antifungal agents used in clinic have many drawbacks and cannot meet the demand of the clinical use. Therefore, for the development of new generation of antifungal agents, it is of great significance to find antifungal lead compounds with novel chemical scaffolds and new mode of action. Novel antifungal lead compounds reported in recent years are reviewed. Their chemical structures, antifungal activity and structure-activity relationship are discussed in detail, and current problems and trends in future research are also emphasized. PMID:18300466

  4. Human Pharmacogenomic Variations and Their Implications for Antifungal Efficacy

    PubMed Central

    Meletiadis, Joseph; Chanock, Stephen; Walsh, Thomas J.

    2006-01-01

    Pharmacogenomics is defined as the study of the impacts of heritable traits on pharmacology and toxicology. Candidate genes with potential pharmacogenomic importance include drug transporters involved in absorption and excretion, phase I enzymes (e.g., cytochrome P450-dependent mixed-function oxidases) and phase II enzymes (e.g., glucuronosyltransferases) contributing to metabolism, and those molecules (e.g., albumin, A1-acid glycoprotein, and lipoproteins) involved in the distribution of antifungal compounds. By using the tools of population genetics to define interindividual differences in drug absorption, distribution, metabolism, and excretion, pharmacogenomic models for genetic variations in antifungal pharmacokinetics can be derived. Pharmacogenomic factors may become especially important in the treatment of immunocompromised patients or those with persistent or refractory mycoses that cannot be explained by elevated MICs and where rational dosage optimization of the antifungal agent may be particularly critical. Pharmacogenomics has the potential to shift the paradigm of therapy and to improve the selection of antifungal compounds and adjustment of dosage based upon individual variations in drug absorption, metabolism, and excretion. PMID:17041143

  5. Research to Identify Effective Antifungal Agents, 1992 Annual Report.

    SciTech Connect

    Schreck, Carl

    1993-03-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990 and Schreck et al. 1991). The objectives of the present study were to select and evaluate up to 10 candidate fungicides.

  6. Simplifungin and Valsafungins, Antifungal Antibiotics of Fungal Origin.

    PubMed

    Ishijima, Hiroyuki; Uchida, Ryuji; Ohtawa, Masaki; Kondo, Ariko; Nagai, Kenichiro; Shima, Keisuke; Nonaka, Kenichi; Masuma, Rokuro; Iwamoto, Susumu; Onodera, Hideyuki; Nagamitsu, Tohru; Tomoda, Hiroshi

    2016-09-01

    The targets of antifungal antibiotics in clinical use are more limited than those of antibacterial antibiotics. Therefore, new antifungal antibiotics with different mechanisms of action are desired. In the course of our screening for antifungal antibiotics of microbial origins, new antifungal antibiotics, simplifungin (1) and valsafungins A (2) and B (3), were isolated from cultures of the fungal strains Simplicillium minatense FKI-4981 and Valsaceae sp. FKH-53, respectively. The structures of 1 to 3 including their absolute stereochemistries were elucidated using various spectral analyses including NMR and collision-induced dissociation (CID)-MS/MS as well as chemical approaches including modifications to the Mosher's method. They were structurally related to myriocin. They inhibited the growth of yeast-like and zygomycetous fungi with MICs ranging between 0.125 and 8.0 μg/mL. An examination of their mechanisms of action by the newly established assay using LC-MS revealed that 1 and 2 inhibited serine palmitoyltransferase activity, which is involved in sphingolipid biosynthesis, with IC50 values of 224 and 24 nM, respectively. PMID:27400027

  7. Synthesis of isosteric triterpenoid derivatives and antifungal activity.

    PubMed

    Innocente, Adrine; Casanova, Bruna B; Klein, Fernanda; Lana, Aline D; Pereira, Dariane; Muniz, Mauro N; Sonnet, Pascal; Gosmann, Grace; Fuentefria, Alexandre M; Gnoatto, Simone C B

    2014-03-01

    Dermatomycoses are among the most widespread and common superficial and cutaneous fungal infections in humans. There is an urgent need to develop efficient and non-toxic antimycotic agents with a specific spectrum of activity. Triterpenes have been demonstrated to exhibit a wide range of biological activities, including antifungal activities. In this study, through hemisynthesis, we aimed to obtain triterpene-isosteric molecules from betulinic and ursolic acids to improve the antifungal activity and spectrum of action of these compounds. Six compounds were resynthesized and tested against eleven mucocutaneous and cutaneous mycotic agents. The results of the susceptibility assays were expressed as the minimal inhibitory concentration (MIC). The MIC values of the piperazinyl derivatives of ursolic and betulinic acids that were active against pathogenic yeasts were in the range of 16-32 μg/mL and 4-16 μg/mL, respectively, whereas fungicidal effects were observed at concentrations ranging from 16 to 128 μg/mL and 8 to 128 μg/mL, respectively. The piperazinyl derivative of betulinic acid exhibited an antifungal profile similar to that of terbinafine and was the most effective derivative against dermatophytes. This strategy led to a promising candidate for the development of a new antifungal agent.

  8. Identification of Ebsulfur Analogues with Broad-Spectrum Antifungal Activity.

    PubMed

    Ngo, Huy X; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2016-07-19

    Invasive fungal infections are on the rise due to an increased population of critically ill patients as a result of HIV infections, chemotherapies, and organ transplantations. Current antifungal drugs are helpful, but are insufficient in addressing the problem of drug-resistant fungal infections. Thus, there is a growing need for novel antimycotics that are safe and effective. The ebselen scaffold has been evaluated in clinical trials and has been shown to be safe in humans. This makes ebselen an attractive scaffold for facile translation from bench to bedside. We recently reported a library of ebselen-inspired ebsulfur analogues with antibacterial properties, but their antifungal activity has not been characterized. In this study, we repurposed ebselen, ebsulfur, and 32 additional ebsulfur analogues as antifungal agents by evaluating their antifungal activity against a panel of 13 clinically relevant fungal strains. The effect of induction of reactive oxygen species (ROS) by three of these compounds was evaluated. Their hemolytic and cytotoxicity activities were also determined using mouse erythrocytes and mammalian cells. The MIC values of these compounds were found to be in the range of 0.02-12.5 μg mL(-1) against the fungal strains tested. Notably, yeast cells treated with our compounds showed an accumulation of ROS, which may further contribute to the growth-inhibitory effect against fungi. This study provides new lead compounds for the development of antimycotic agents. PMID:27334363

  9. Two new antifungal alkaloids produced by Streptoverticillium morookaense.

    PubMed

    Feng, Na; Ye, Wanhui; Wu, Ping; Huang, Yicun; Xie, Haihui; Wei, Xiaoyi

    2007-03-01

    A new carbazole alkaloid, streptoverticillin, and a new 2-azetidinone, streptoverticillinone, along with three known cyclodipeptides were isolated from the mycelial solid culture of Streptoverticillium morookaense. Their structures were elucidated by analysis of 1D and 2D NMR, mass spectra and optical rotation data. Two new compounds exhibited antifungal activity against Peronophythora litchii. PMID:17446689

  10. Activation of Melanin Synthesis in Alternaria infectoria by Antifungal Drugs

    PubMed Central

    Fernandes, Chantal; Prados-Rosales, Rafael; Silva, Branca M. A.; Nakouzi-Naranjo, Antonio; Zuzarte, Mónica; Chatterjee, Subhasish; Stark, Ruth E.; Casadevall, Arturo

    2015-01-01

    The importance of Alternaria species fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on Alternaria infectoria, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced by A. infectoria, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate that A. infectoria increased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate that A. infectoria activates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organized A. infectoria cell walls. In summary, A. infectoria synthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis. PMID:26711773

  11. Using Aspergillus nidulans to identify antifungal drug resistance mutations.

    PubMed

    He, Xiaoxiao; Li, Shengnan; Kaminskyj, Susan G W

    2014-02-01

    Systemic fungal infections contribute to at least 10% of deaths in hospital settings. Most antifungal drugs target ergosterol (polyenes) or its biosynthetic pathway (azoles and allylamines), or beta-glucan synthesis (echinocandins). Antifungal drugs that target proteins are prone to the emergence of resistant strains. Identification of genes whose mutations lead to targeted resistance can provide new information on those pathways. We used Aspergillus nidulans as a model system to exploit its tractable sexual cycle and calcofluor white as a model antifungal agent to cross-reference our results with other studies. Within 2 weeks from inoculation on sublethal doses of calcofluor white, we isolated 24 A. nidulans adaptive strains from sectoring colonies. Meiotic analysis showed that these strains had single-gene mutations. In each case, the resistance was specific to calcofluor white, since there was no cross-resistance to caspofungin (echinocandin). Mutation sites were identified in two mutants by next-generation sequencing. These were confirmed by reengineering the mutation in a wild-type strain using a gene replacement strategy. One of these mutated genes was related to cell wall synthesis, and the other one was related to drug metabolism. Our strategy has wide application for many fungal species, for antifungal compounds used in agriculture as well as health care, and potentially during protracted drug therapy once drug resistance arises. We suggest that our strategy will be useful for keeping ahead in the drug resistance arms race. PMID:24363365

  12. Prediction of Antifungal Activity of Gemini Imidazolium Compounds

    PubMed Central

    Pałkowski, Łukasz; Błaszczyński, Jerzy; Skrzypczak, Andrzej; Błaszczak, Jan; Nowaczyk, Alicja; Wróblewska, Joanna; Kożuszko, Sylwia; Gospodarek, Eugenia; Słowiński, Roman; Krysiński, Jerzy

    2015-01-01

    The progress of antimicrobial therapy contributes to the development of strains of fungi resistant to antimicrobial drugs. Since cationic surfactants have been described as good antifungals, we present a SAR study of a novel homologous series of 140 bis-quaternary imidazolium chlorides and analyze them with respect to their biological activity against Candida albicans as one of the major opportunistic pathogens causing a wide spectrum of diseases in human beings. We characterize a set of features of these compounds, concerning their structure, molecular descriptors, and surface active properties. SAR study was conducted with the help of the Dominance-Based Rough Set Approach (DRSA), which involves identification of relevant features and relevant combinations of features being in strong relationship with a high antifungal activity of the compounds. The SAR study shows, moreover, that the antifungal activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds. We also show that molecular descriptors MlogP, HOMO-LUMO gap, total structure connectivity index, and Wiener index may be useful in prediction of antifungal activity of new chemical compounds. PMID:25961015

  13. Antifungal activity of heartwood extracts from three Juniperus species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heartwood samples from three species of Juniperus (i.e., J. virginianna, J. occidentalis, and J. ashei) were extracted with hexane, ethanol and methanol and the hexane and ethanol extracts were tested for antifungal activity against four species of wood-rot fungi. These three species represent the ...

  14. Chemosensitization as a means to augment commercial antifungal agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is growing list of papers on antimycotic chemosensitization and the mechanisms by which they function. Currently, antifungal agents used in agriculture and in human or veterinary medicine are confronted by a number of obstacles, the main one being continual development of resistance to one, or...

  15. Identification and biological activity of antifungal saponins from shallot ( Allium cepa L. Aggregatum group).

    PubMed

    Teshima, Yoshiki; Ikeda, Tsuyoshi; Imada, Kiyoshi; Sasaki, Kazunori; El-Sayed, Magdi A; Shigyo, Masayoshi; Tanaka, Shuhei; Ito, Shin-Ichi

    2013-08-01

    The n-butanol extract of shallot basal plates and roots showed antifungal activity against plant pathogenic fungi. The purified compounds from the extract were examined for antifungal activity to determine the predominant antifungal compounds in the extract. Two major antifungal compounds purified were determined to be alliospiroside A (ALA) and alliospiroside B. ALA had prominent antifungal activity against a wide range of fungi. The products of acid hydrolysis of ALA showed a reduced antifungal activity, suggesting that the compound's sugar chain is essential for its antifungal activity. Fungal cells treated with ALA showed rapid production of reactive oxygen species. The fungicidal action of ALA was partially inhibited by a superoxide scavenger, Tiron, suggesting that superoxide anion generation in the fungal cells may be related to the compound's action. Inoculation experiments showed that ALA protected strawberry plants against Colletotrichum gloeosporioides , indicating that ALA has the potential to control anthracnose of the plant.

  16. Antifungal effect and action mechanism of antimicrobial peptide polybia-CP.

    PubMed

    Wang, Kairong; Jia, Fengjing; Dang, Wen; Zhao, Yanyan; Zhu, Ranran; Sun, Mengyang; Qiu, Shuai; An, Xiaoping; Ma, Zelin; Zhu, Yuanyuan; Yan, Jiexi; Kong, Ziqing; Yan, Wenjin; Wang, Rui

    2016-01-01

    The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option. PMID:26680221

  17. Identification and biological activity of antifungal saponins from shallot ( Allium cepa L. Aggregatum group).

    PubMed

    Teshima, Yoshiki; Ikeda, Tsuyoshi; Imada, Kiyoshi; Sasaki, Kazunori; El-Sayed, Magdi A; Shigyo, Masayoshi; Tanaka, Shuhei; Ito, Shin-Ichi

    2013-08-01

    The n-butanol extract of shallot basal plates and roots showed antifungal activity against plant pathogenic fungi. The purified compounds from the extract were examined for antifungal activity to determine the predominant antifungal compounds in the extract. Two major antifungal compounds purified were determined to be alliospiroside A (ALA) and alliospiroside B. ALA had prominent antifungal activity against a wide range of fungi. The products of acid hydrolysis of ALA showed a reduced antifungal activity, suggesting that the compound's sugar chain is essential for its antifungal activity. Fungal cells treated with ALA showed rapid production of reactive oxygen species. The fungicidal action of ALA was partially inhibited by a superoxide scavenger, Tiron, suggesting that superoxide anion generation in the fungal cells may be related to the compound's action. Inoculation experiments showed that ALA protected strawberry plants against Colletotrichum gloeosporioides , indicating that ALA has the potential to control anthracnose of the plant. PMID:24138065

  18. Antifungal effect and action mechanism of antimicrobial peptide polybia-CP.

    PubMed

    Wang, Kairong; Jia, Fengjing; Dang, Wen; Zhao, Yanyan; Zhu, Ranran; Sun, Mengyang; Qiu, Shuai; An, Xiaoping; Ma, Zelin; Zhu, Yuanyuan; Yan, Jiexi; Kong, Ziqing; Yan, Wenjin; Wang, Rui

    2016-01-01

    The incidence of life-threatening invasive fungal infections increased significantly in recent years. However, the antifungal therapeutic options are very limited. Antimicrobial peptides are a class of potential lead chemical for the development of novel antifungal agents. Antimicrobial peptide polybia-CP was purified from the venom of the social wasp Polybia paulista. In this study, we synthesized polybia-CP and determined its antifungal effects against a series of Candidian species. Our results showed that polybia-CP has potent antifungal activity and fungicidal activity against the tested fungal cells with a proposed membrane-active action mode. In addition, polybia-CP could induce the increase of cellular reactive oxygen species production, which would attribute to its antifungal activity. In conclusion, the present study suggests that polybia-CP has potential as an antifungal agent or may offer a new strategy for antifungal therapeutic option.

  19. Disruption of testosterone homeostasis as a mode of action for the reproductive toxicity of triazole fungicides in the male rat.

    PubMed

    Goetz, Amber K; Ren, Hongzu; Schmid, Judith E; Blystone, Chad R; Thillainadarajah, Inthirany; Best, Deborah S; Nichols, Harriette P; Strader, Lillian F; Wolf, Douglas C; Narotsky, Michael G; Rockett, John C; Dix, David J

    2007-01-01

    Triazole fungicides associated with a range of reported male reproductive effects in experimental animals were selected to assess potential toxic modes of action. Wistar Han rats were fed myclobutanil (M: 100, 500, or 2000 ppm), propiconazole (P: 100, 500, or 2500 ppm), or triadimefon (T: 100, 500, or 1800 ppm) from gestation day 6 to postnatal day (PND) 120. One male per litter was necropsied on PND1, 22, 50, or 92. Measurements included anogenital distance (AGD) at PND0, body and organ weights, serum hormone levels, age at preputial separation (PPS), sperm morphology and motility, and fertility and fecundity. AGD was increased by the high dose of all three triazoles, indicating hypervirilization. Triadimefon delayed PPS, consistent with delayed puberty, at 1800 ppm. Relative liver weights were increased at PND1, 50, and 92 by all three triazoles. Hepatocellular hypertrophy was present at PND50 from propiconazole and triadimefon and at PND92 from all three high-dose triazole treatments. Relative pituitary weights were decreased at PND92 by middle- and high-dose myclobutanil treatment. Absolute testis weights were increased at PND1 by myclobutanil, at PND22 by myclobutanil and triadimefon, and at PND50 by propiconazole and triadimefon treatment. Relative ventral prostate weights were increased at PND92 by myclobutanil and triadimefon treatment. Serum testosterone was increased at PND50 by triadimefon and at PND92/99 by all three triazole treatments. Insemination and fertility were impaired by myclobutanil and triadimefon treatment. In addition to the reproductive system effects, total serum thyroxine levels were decreased at PND92 by high-dose triadimefon. These reproductive effects are consistent with the disruption of testosterone homeostasis as a key event in the mode of action for triazole-induced reproductive toxicity.

  20. Sporothrix schenckii complex in Iran: Molecular identification and antifungal susceptibility.

    PubMed

    Mahmoudi, Shahram; Zaini, Farideh; Kordbacheh, Parivash; Safara, Mahin; Heidari, Mansour

    2016-08-01

    Sporotrichosis is a global subcutaneous fungal infection caused by the Sporothrix schenckii complex. Sporotrichosis is an uncommon infection in Iran, and there have been no phenotypic, molecular typing or antifungal susceptibility studies of Sporothrix species. This study aimed to identify nine Iranian isolates of the S. schenckii complex to the species level using colony morphology, carbohydrate assimilation tests, and PCR-sequencing of the calmodulin gene. The antifungal susceptibilities of these Sporothrix isolates to five antifungal agents (amphotericin B (AMB), voriconazole (VRC), itraconazole (ITC), fluconazole (FLC), and terbinafine (TRB)) were also evaluated according to the M27-A3 and M38-A2 protocols of the Clinical and Laboratory Standards Institute for yeast and mycelial phases, respectively. Five of seven clinical isolates were identified as S. schenckii, and two clinical and two environmental isolates were identified as S. globosa. This is the first report of S. globosa in Iran. There was significant agreement (73%) between the results of the phenotypic and genotypic identification methods. TRB and ITC were the most effective antifungals against the Sporothrix isolates. The minimum inhibitory concentration (MIC) values of TRB for the yeast and mycelial phases of S. schenckii differed significantly. There was also a significant difference in the minimum fungicidal concentration (MFC) values of AMB and TRB for the two phases. Considering the low efficacy of VRC and FLC and the wide MIC ranges of AMB (1-16 μg/ml and 1-8 μg/ml for yeast and mycelial forms, respectively) observed in the present study, in vitro antifungal susceptibility testing should be performed to determine appropriate therapeutic regimens.

  1. In Vitro Antifungal Activities against Moulds Isolated from Dermatological Specimens

    PubMed Central

    Mohd Nizam, Tzar; Binting, Rabiatul Adawiyah AG.; Mohd Saari, Shafika; Kumar, Thivyananthini Vijaya; Muhammad, Marianayati; Satim, Hartini; Yusoff, Hamidah; Santhanam, Jacinta

    2016-01-01

    Background This study aimed to determine the minimum inhibitory concentrations (MICs) of various antifungal agents against moulds isolated from dermatological specimens. Methods We identified 29 moulds from dermatological specimens between October 2012 and March 2013 by conventional methods. We performed antifungal susceptibility testing on six antifungal agents, amphotericin B, clotrimazole, itraconazole, ketoconazole, miconazole and terbinafine, according to the Clinical and Laboratory Standards Institute guidelines contained in the M38-A2 document. Results Most antifungal agents were active against the dermatophytes, except for terbinafine against Trichophyton rubrum (geometric mean MIC, MICGM 3.17 μg/mL). The dematiaceous moulds were relatively susceptible to amphotericin B and azoles (MICGM 0.17–0.34 μg/mL), but not to terbinafine (MICGM 3.62 μg/mL). Septate hyaline moulds showed variable results between the relatively more susceptible Aspergillus spp. (MICGM 0.25–4 μg/mL) and the more resistant Fusarium spp. (MICGM 5.66–32 μg/mL). The zygomycetes were susceptible to amphotericin B (MICGM 0.5 μg/mL) and clotrimazole (MICGM 0.08 μg/mL), but not to other azoles (MICGM 2.52–4 μg/mL). Conclusion Amphotericin B and clotrimazole were the most effective antifungal agents against all moulds excepting Fusarium spp., while terbinafine was useful against dermatophytes (except T. rubrum) and Aspergillus spp. However, a larger study is required to draw more solid conclusions. PMID:27418867

  2. Evaluation of the antifungal activity and modulation between Cajanus cajan (L.) Millsp. leaves and roots ethanolic extracts and conventional antifungals

    PubMed Central

    Brito, Samara A.; Rodrigues, Fabíola F. G.; Campos, Adriana R.; da Costa, José G. M.

    2012-01-01

    Background: The use and investigation of natural products with antimicrobial activity from vegeral source have been reported by several researchers. Cajanus cajan (Fabaceae) is a multiple use specie mainly as human food. In popular medicine, diverse parts of the plant are used as sedative and to treat cough, hepatitis, and diabetes. Materials and Methods: This study shows the characterization of secondary metabolites present in ehtanolic extracts from leaves and roots of Cajanus cajan by phytochemical prospection. The evaluation of the antifungal activity was performed by the microdilution method, and from the subinhibitory concentrations (MIC 1/8) the modulatory activity of antifungical (fluconazole and ketoconazole) was analyzed by the direct contact assay against C. albicans ATCC40006, Candida krusei ATCC 6538 and Candida tropicalis ATCC 40042. Results: The results showed the presence of tannins, flavonoids, and alkaloids in both extracts as the clinically relevant antifungal activity. The modulatory potential is presented by the antifungal tested against yeasts. Conclusion: The extracts studied here have demonstrated to be a new therapeutic source to treat these microorganism-associated diseases. PMID:22701281

  3. Conventional and alternative antifungal therapies to oral candidiasis.

    PubMed

    Anibal, Paula Cristina; de Cássia Orlandi Sardi, Janaina; Peixoto, Iza Teixeira Alves; de Carvalho Moraes, Julianna Joanna; Höfling, José Francisco

    2010-10-01

    Candida-associated denture stomatitis is the most common form of oral candidal infection, with Candida albicans being the principal etiological agent. Candida adheres directly or via an intermediary layer of plaque-forming bacteria to denture acrylic. Despite antifungal therapy to treat denture stomatitis, infection is reestablished soon after the treatment ceases. In addition, many predisposing factors have been identified as important in the development of oral candidiasis, including malnourishment, common endocrine disorders, such as diabetis mellitus, antibacterial drug therapy, corticosteroids, radiotherapy and other immunocompromised conditions, such as acquired immunodeficiency syndrome (AIDS). These often results in increased tolerance to the most commonly used antifungals. So this review suggests new therapies to oral candidiasis.

  4. Synthesis of heterocycle-attached methylidenebenzenesulfonohydrazones as antifungal agents.

    PubMed

    Gao, Zhinan; Lv, Min; Li, Qin; Xu, Hui

    2015-11-15

    A series of heterocycle-attached methylidenebenzenesulfonohydrazone derivatives were synthesized and evaluated for their antifungal activities against seven phytopathogenic fungi such as Fusarium graminearum, Alternaria solani, Valsa mali, Phytophthora capsici, Fusarium solani, Botrytis cinerea, and Glomerella cingulata. Compounds 7b, 8d, 9a, 9b and 9d exhibited a good and broad-spectrum of antifungal activities against at least five phytopathogenic fungi at the concentration of 100 μg/mL. It demonstrated that addition of one double bond between the phenylsulfonylhydrazone fragment and the furan ring of 6a,b,d could afford more active compounds 9a,b,d; however, introduction of the nitro group on the phenyl ring of 6a-9a gave less potent compounds 6e-9e. PMID:26471091

  5. Synthesis of chitosan derivative with diethyldithiocarbamate and its antifungal activity.

    PubMed

    Qin, Yukun; Xing, Ronge; Liu, Song; Li, Kecheng; Hu, Linfeng; Yu, Huahua; Chen, Xiaolin; Li, Pengcheng

    2014-04-01

    With an aim to discover novel chitosan derivatives with enhanced antifungal properties compared with chitosan. Diethyl dithiocarbamate chitosan (EtDTCCS) was investigated and its structure was well identified. The antifungal activity of EtDTCCS against Alternaria porri (A. porri), Gloeosporium theae sinensis Miyake (G. theae sinensis), and Stemphylium solani Weber (S. solani) was tested at 0.25, 0.5, and 1.0 mg/mL, respectively. Compared with plain chitosan, EtDTCCS shows better inhibitory effect with 93.2% inhibitory index on G. theae sinensis at 1.0 mg/mL, even stronger than for polyoxin (82.5%). It was inferred derivatives of this kind may find potential applications for the treatment of various crop-threatening diseases. PMID:24530333

  6. BIOSYNTHESIS OF MYCOBACILLIN, A NEW ANTIFUNGAL PEPTIDE I.

    PubMed Central

    Banerjee, Arun B.; Bose, S. K.

    1964-01-01

    Banerjee, Arun B. (University of Calcutta, Calcutta, India), and S. K. Bose. Biosynthesis of mycobacillin, a new antifungal peptide. I. Role of nucleic acid. J. Bacteriol. 87:1397–1401. 1964.—The biosynthesis of mycobacillin, a cyclic polypeptide antifungal antibiotic, was studied in relation to the effect of chloramphenicol, 6-azathymine, and 5-bromouracil on the process. It was found that chloramphenicol inhibits both mycobacillin synthesis and growth, whereas nucleic acid base analogues inhibit only growth and nucleic acid synthesis but not mycobacillin formation. A change in the concentration of labeled aspartic acid in the general metabolic pool led to a corresponding change in the specific activity of aspartic acid isolated from different peptide fragments of the mycobacillin molecule, suggesting that mycobacillin synthesis occurs by way of linear addition of amino acid to the peptide chain. PMID:14188719

  7. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani

    PubMed Central

    Zhang, Xiaohui; Jacob, Melissa R; Rao, R Ranga; Wang, Yan-Hong; Agarwal, Ameeta K; Newman, David J; Khan, Ikhlas A; Clark, Alice M; Li, Xing-Cong

    2013-01-01

    Screening natural product extracts from the National Cancer Institute Open Repository for antifungal discovery afforded hits for bioassay-guided fractionation. Using LC–MS analysis to generate chemical structure information on potentially active compounds, two new cyclic hexapeptides, microsclerodermins J (1) and K (2), were isolated from the deep-water sponge Microscleroderma herdmani, along with microsclerodermins A (3) and B (4), previously isolated from an unidentified Microscleroderma species. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. In vitro antifungal testing showed that the four compounds possessed strong activities against the opportunistic fungal pathogens Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and Aspergillus fumigatus. PMID:23936761

  8. Inhibitors of amino acids biosynthesis as antifungal agents.

    PubMed

    Jastrzębowska, Kamila; Gabriel, Iwona

    2015-02-01

    Fungal microorganisms, including the human pathogenic yeast and filamentous fungi, are able to synthesize all proteinogenic amino acids, including nine that are essential for humans. A number of enzymes catalyzing particular steps of human-essential amino acid biosynthesis are fungi specific. Numerous studies have shown that auxotrophic mutants of human pathogenic fungi impaired in biosynthesis of particular amino acids exhibit growth defect or at least reduced virulence under in vivo conditions. Several chemical compounds inhibiting activity of one of these enzymes exhibit good antifungal in vitro activity in minimal growth media, which is not always confirmed under in vivo conditions. This article provides a comprehensive overview of the present knowledge on pathways of amino acids biosynthesis in fungi, with a special emphasis put on enzymes catalyzing particular steps of these pathways as potential targets for antifungal chemotherapy.

  9. Virulence and Resistance to Antifungal Therapies of Scopulariopsis Species

    PubMed Central

    Paredes, Katihuska; Mayayo, Emilio; Guarro, Josep

    2016-01-01

    Scopulariopsis is an emerging opportunistic fungus characterized by its high resistance to antifungal therapies. We have developed a murine model of disseminated infection in immunosuppressed animals by intravenous inoculation of Scopulariopsis brevicaulis and Scopulariopsis brumptii, the most clinically relevant species, in order to evaluate their virulence and their responses to conventional antifungal treatments. Survival and tissue burden studies showed that S. brumptii was more virulent than S. brevicaulis. The three drugs tested, liposomal amphotericin B, posaconazole, and voriconazole, prolonged the survival of mice infected with S. brumptii, but none showed efficacy against S. brevicaulis. The different therapies were only able to modestly reduce the fungal burden of infected tissue; however, in general, despite the high serum levels reached, they showed poor efficacy in the treatment of the infection. Unfortunately, the most effective therapy for Scopulariopsis infections remains unresolved. PMID:26787688

  10. Conventional and alternative antifungal therapies to oral candidiasis

    PubMed Central

    Anibal, Paula Cristina; de Cássia Orlandi Sardi, Janaina; Peixoto, Iza Teixeira Alves; de Carvalho Moraes, Julianna Joanna; Höfling, José Francisco

    2010-01-01

    Candida-associated denture stomatitis is the most common form of oral candidal infection, with Candida albicans being the principal etiological agent. Candida adheres directly or via an intermediary layer of plaque-forming bacteria to denture acrylic. Despite antifungal therapy to treat denture stomatitis, infection is reestablished soon after the treatment ceases. In addition, many predisposing factors have been identified as important in the development of oral candidiasis, including malnourishment, common endocrine disorders, such as diabetis mellitus, antibacterial drug therapy, corticosteroids, radiotherapy and other immunocompromised conditions, such as acquired immunodeficiency syndrome (AIDS). These often results in increased tolerance to the most commonly used antifungals. So this review suggests new therapies to oral candidiasis. PMID:24031562

  11. Purification of castamollin, a novel antifungal protein from Chinese chestnuts.

    PubMed

    Wang, H X; Ng, T B

    2003-11-01

    A novel antifungal protein, designated castamollin, was isolated from Chinese chestnut (Castanea mollisima) seeds with a procedure involving ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-Sepharose and FPLC-gel filtration on Superdex 75. Castamollin possessed a novel N-terminal sequence demonstrating little similarity to N-terminal sequences of Castanea sativa chitinase. Castamollin exhibited a molecular mass of 37kDa in gel filtration and SDS-PAGE. It inhibited the activity of human immunodeficiency virus-1 reverse transcriptase with an IC(50) of 7microM and translation in a cell-free rabbit reticulocyte lysate system with an IC(50) of 2.7microM. Castamollin displayed antifungal activity against Botrytis cinerea, Mycosphaerella arachidicola, Physalospora piricola, and Coprinus comatus but was devoid of lectin activity.

  12. Synthesis, antifungal activity, and QSAR study of novel trichodermin derivatives.

    PubMed

    Cheng, Jing-Li; Zheng, Min; Yao, Ting-Ting; Li, Xiao-Liang; Zhao, Jin-Hao; Xia, Min; Zhu, Guo-Nian

    2015-01-01

    In an attempt to discover more potential antifungal agents, in this study, 21 novel trichodermin derivatives containing conjugated oxime ester (5a-5u) were designed and synthesized and were screened for in vitro antifungal activity. The bioassay tests showed that some of them exhibited good inhibitory activity against the tested pathogenic fungi. Compound 5a exhibited better activity against Pyricularia oryzae and Sclerotonia sclerotiorum than trichodermin, and compound 5j showed particular activity against P.oryzae and Botrytis cinerea. The quantitative structure-activity relationship (QSAR) indicated that log P and hardness were two critical parameters for the biological activities. The result suggested that these would be potential lead compounds for the development of fungicides with further structure modification. PMID:25290081

  13. [Composition, antifungal and radical scavenging activities of 4 propolis].

    PubMed

    Inouye, Shigeharu; Takahashi, Miki; Abe, Shigeru

    2011-01-01

    HPLC/MS analysis revealed that the main constituents of Brazilian propolis A and B were artepillin C and drupanin, while those of New Zealand propolis C were pinocembrin, galangin and alkylphenol. No flavonoid or phenolic acid was detected in Japanese propolis D. Propolis C showed comparatively potent activity against growth of Trichophyton mentagrophytes, against filament formation of Candida albicans and potent scavenging activity against 1,1-diphenyl-2-picrylhyrazyl radical, but was less active against growth of C. albicans, as compared with those of thyme thymol essential oil, which was used as a positive control. Propolis A, B, and D were weak in antifungal activity, but showed more potent radical scavenging activity than thyme thymol oil. These results reveal the unique bioactivity of propolis, suggesting a possible application for antifungal therapy. PMID:22123329

  14. Antifungal amphiphilic aminoglycoside K20: bioactivities and mechanism of action

    PubMed Central

    Shrestha, Sanjib K.; Chang, Cheng-Wei T.; Meissner, Nicole; Oblad, John; Shrestha, Jaya P.; Sorensen, Kevin N.; Grilley, Michelle M.; Takemoto, Jon Y.

    2014-01-01

    K20 is a novel amphiphilic antifungal aminoglycoside that is synthetically derived from the antibiotic kanamycin A. Reported here are investigations of K20′s antimicrobial activities, cytotoxicity, and fungicidal mechanism of action. In vitro growth inhibitory activities against a variety of human and plant pathogenic yeasts, filamentous fungi, and bacteria were determined using microbroth dilution assays and time-kill curve analyses, and hemolytic and animal cell cytotoxic activities were determined. Effects on Cryptococcus neoformans H-99 infectivity were determined with a preventive murine lung infection model. The antifungal mechanism of action was studied using intact fungal cells, yeast lipid mutants, and small unilamellar lipid vesicles. K20 exhibited broad-spectrum in vitro antifungal activities but not antibacterial activities. Pulmonary, single dose-administration of K20 reduced C. neoformans lung infection rates 4-fold compared to controls. Hemolysis and half-maximal cytotoxicities of mammalian cells occurred at concentrations that were 10 to 32-fold higher than fungicidal MICs. With fluorescein isothiocyanate (FITC), 20–25 mg/L K20 caused staining of >95% of C. neoformans and Fusarium graminearum cells and at 31.3 mg/L caused rapid leakage (30–80% in 15 min) of calcein from preloaded small unilamellar lipid vesicles. K20 appears to be a broad-spectrum fungicide, capable of reducing the infectivity of C. neoformans, and exhibits low hemolytic activity and mammalian cell toxicity. It perturbs the plasma membrane by mechanisms that are lipid modulated. K20 is a novel amphiphilic aminoglycoside amenable to scalable production and a potential lead antifungal for therapeutic and crop protection applications. PMID:25538692

  15. Trichoharzianol, a new antifungal from Trichoderma harzianum F031.

    PubMed

    Jeerapong, Chotika; Phupong, Worrapong; Bangrak, Phuwadol; Intana, Warin; Tuchinda, Patoomratana

    2015-04-15

    A new decalin derivative, trichoharzianol (1), together with three known compounds, eujavanicol A (2), 5-hydroxy-3-hydroxymethyl-2-methyl-7-methoxychromone (3), and 4,6-dihydroxy-5-methylphthalide (4), were isolated from Trichoderma harzianum F031. For the first time, compounds 2-4 were reported from the Trichoderma species. Their structures were characterized by spectroscopic methods. Trichoharzianol (1) showed the highest antifungal activity against Colletotrichum gloeosporioides, with a minimum inhibitory concentration (MIC) of 128 μg/mL.

  16. Antifungal amphiphilic aminoglycoside K20: bioactivities and mechanism of action.

    PubMed

    Shrestha, Sanjib K; Chang, Cheng-Wei T; Meissner, Nicole; Oblad, John; Shrestha, Jaya P; Sorensen, Kevin N; Grilley, Michelle M; Takemoto, Jon Y

    2014-01-01

    K20 is a novel amphiphilic antifungal aminoglycoside that is synthetically derived from the antibiotic kanamycin A. Reported here are investigations of K20's antimicrobial activities, cytotoxicity, and fungicidal mechanism of action. In vitro growth inhibitory activities against a variety of human and plant pathogenic yeasts, filamentous fungi, and bacteria were determined using microbroth dilution assays and time-kill curve analyses, and hemolytic and animal cell cytotoxic activities were determined. Effects on Cryptococcus neoformans H-99 infectivity were determined with a preventive murine lung infection model. The antifungal mechanism of action was studied using intact fungal cells, yeast lipid mutants, and small unilamellar lipid vesicles. K20 exhibited broad-spectrum in vitro antifungal activities but not antibacterial activities. Pulmonary, single dose-administration of K20 reduced C. neoformans lung infection rates 4-fold compared to controls. Hemolysis and half-maximal cytotoxicities of mammalian cells occurred at concentrations that were 10 to 32-fold higher than fungicidal MICs. With fluorescein isothiocyanate (FITC), 20-25 mg/L K20 caused staining of >95% of C. neoformans and Fusarium graminearum cells and at 31.3 mg/L caused rapid leakage (30-80% in 15 min) of calcein from preloaded small unilamellar lipid vesicles. K20 appears to be a broad-spectrum fungicide, capable of reducing the infectivity of C. neoformans, and exhibits low hemolytic activity and mammalian cell toxicity. It perturbs the plasma membrane by mechanisms that are lipid modulated. K20 is a novel amphiphilic aminoglycoside amenable to scalable production and a potential lead antifungal for therapeutic and crop protection applications.

  17. Efficacy of some natural compounds as antifungal agents

    PubMed Central

    Vengurlekar, Sudha; Sharma, Rajesh; Trivedi, Piyush

    2012-01-01

    Natural sources have been important for the development of new active molecules for many years. Various small molecules with unique chemical skeleton and potent bioactivities were discovered through various sources like plants, marine products, and microorganisms, etc., which are considered as very important part of the nature. A number of potent antifungals have been originated from various natural sources. This account describes structure and activities of selected agents isolated from various natural sources. PMID:23055634

  18. Experimental evaluation of antifungal and antiseptic agents against Rhodotorula spp.

    PubMed

    Preney, L; Théraud, M; Guiguen, C; Gangneux, J P

    2003-12-01

    We studied the susceptibility of 21 strains of Rhodotorula rubra and nine strains of R. glutinis to eight antifungals and tested eight antiseptic agents on one strain of R. rubra. The tested strains were susceptible to ketoconazole, 5-fluorocytosine, amphotericin B, and nystatin, intermediate to econazole and resistant to fluconazole, itraconazole and miconazole. After 5-min contact, six of the eight antiseptic agents tested showed a fungicidal activity on the tested R. rubra strain.

  19. Synthesis and antifungal activity of cinnamic acid esters.

    PubMed

    Tawata, S; Taira, S; Kobamoto, N; Zhu, J; Ishihara, M; Toyama, S

    1996-05-01

    Cinnamic, p-coumaric and ferulic acids were isolated from pineapple stems (Ananas comosus var. Cayenne). Twenty-four kinds of esters were prepared from these acids, alcohols and the components of Alpinia. Isopropyl 4-hydroxycinnamate (11) and butyl 4-hydroxycinnamate (12) were found to have almost the same effectiveness in antifungal activity against Pythium sp. at 10 ppm as that of the commercial fungicide iprobenfos (kitazin P).

  20. Antifungal and anthelmintic activities of Cleistopholis patens (Annonaceae).

    PubMed

    Akendengué, Blandine; Champy, Pierre; Nzamba, Joseph; Roblot, François; Loiseau, Philippe M; Bories, Christian

    2009-08-01

    Basic CH2Cl2 extract of the trunk bark of Cleistopholis patens (Annonaceae) exhibited antifungal activities against Candida albicans, C. parapsilosis, and C. glabrata using an agar well-diffusion assay method. Bioassay-guided fractionation of the extract led to the isolation of 8-hydroxysampangine. The methanolic extract displayed anthelmintic activity against Rhabditis pseudoelongata. Purification of the neutral CH2Cl2 extract yielded bornyl-p-transcoumarate and bornyl-p-cis-coumarate.

  1. Antifungal activity of tuberose absolute and some of its constituents.

    PubMed

    Nidiry, Eugene Sebastian J; Babu, C S Bujji

    2005-05-01

    The antifungal activity of the absolute of tuberose (Polianthes tuberosa ) and some of its constituents were evaluated against the mycelial growth of Colletotrichum gloeosporioides on potato-dextrose-agar medium. Tuberose absolute showed only mild activity at a concentration of 500 mg/L. However, three constituents present in the absolute, namely geraniol, indole and methyl anthranilate exhibited significant activity showing total inhibition of the mycelial growth at this concentration.

  2. Synthesis of Novel Pyrimethanil Grafted Chitosan Derivatives with Enhanced Antifungal Activity

    PubMed Central

    Liu, Song; Xing, Ronge; Chen, Xiaolin

    2016-01-01

    In this study, three pyrimethanil grafted chitosan (PML-g-CS) derivatives were obtained. The structures of the conjugates were confirmed by FT-IR, 1H NMR, and EA. The grafting ratios were measured by HPLC. Antifungal properties of pyrimethanil grafted chitosan (PML-g-CS) derivatives against the plant pathogenic fungi Rhizoctonia solani and Gibberella zeae were investigated at concentrations of 100, 200, and 400 mg/L. The PML-g-CS derivatives showed enhanced antifungal activity in comparison with chitosan. The PML-g-CS-1 showed the best antifungal activity against R. solani, whose antifungal index was 58.32%. The PML-g-CS-2 showed the best antifungal activity against G. zeae, whose antifungal index was 53.48%. The conjugation of chitosan and pyrimethanil showed synergistic effect. The PML-g-CS derivatives we developed showed potential for further study and application in crop protection. PMID:27529072

  3. The fungal resistome: a risk and an opportunity for the development of novel antifungal therapies.

    PubMed

    Reales-Calderón, Jose A; Molero, Gloria; Gil, Concha; Martínez, José L

    2016-08-01

    The risks for toxicity of novel antifungal compounds, together with the emergence of resistance, makes the use of inhibitors of resistance, in combination with antifungal compounds, a suitable strategy for developing novel antifungal formulations. Among them, inhibitors of efflux pumps are suitable candidates. Increasing drug influx or interfering with the stress response may also improve the efficacy of antifungals. Therapies as induction of fungal apoptosis or immunostimulation are also good strategies for reducing the risks for resistance and to improve antifungals' efficacy. Understanding the effect of the acquisition of resistance on the fungal physiology and determining the collateral sensitivity networks are useful for the development of novel strategies based on combination of antifungals for improving the efficacy of the therapy. PMID:27485839

  4. Phylogenetic Relationships Matter: Antifungal Susceptibility among Clinically Relevant Yeasts

    PubMed Central

    Schmalreck, A. F.; Becker, K.; Fegeler, W.; Czaika, V.; Ulmer, H.; Lass-Flörl, C.

    2014-01-01

    The objective of this study was 2-fold: to evaluate whether phylogenetically closely related yeasts share common antifungal susceptibility profiles (ASPs) and whether these ASPs can be predicted from phylogeny. To address this question, 9,627 yeast strains were collected and tested for their antifungal susceptibility. Isolates were reidentified by considering recent changes in taxonomy and nomenclature. A phylogenetic (PHYLO) code based on the results of multilocus sequence analyses (large-subunit rRNA, small-subunit rRNA, translation elongation factor 1α, RNA polymerase II subunits 1 and 2) and the classification of the cellular neutral sugar composition of coenzyme Q and 18S ribosomal DNA was created to group related yeasts into PHYLO groups. The ASPs were determined for fluconazole, itraconazole, and voriconazole in each PHYLO group. The majority (95%) of the yeast strains were Ascomycetes. After reclassification, a total of 23 genera and 54 species were identified, resulting in an increase of 64% of genera and a decrease of 5% of species compared with the initial identification. These taxa were assigned to 17 distinct PHYLO groups (Ascomycota, n = 13; Basidiomycota, n = 4). ASPs for azoles were similar among members of the same PHYLO group and different between the various PHYLO groups. Yeast phylogeny may be an additional tool to significantly enhance the assessment of MIC values and to predict antifungal susceptibility, thereby more rapidly initiating appropriate patient management. PMID:24366735

  5. An overview of antifungal peptides derived from insect.

    PubMed

    Faruck, Mohammad Omer; Yusof, Faridah; Chowdhury, Silvia

    2016-06-01

    Fungi are not classified as plants or animals. They resemble plants in many ways but do not produce chlorophyll or make their own food photosynthetically like plants. Fungi are useful for the production of beer, bread, medicine, etc. More complex than viruses or bacteria; fungi can be destructive human pathogens responsible for various diseases in humans. Most people have a strong natural immunity against fungal infection. However, fungi can cause diseases when this immunity breaks down. In the last few years, fungal infection has increased strikingly and has been accompanied by a rise in the number of deaths of cancer patients, transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients owing to fungal infections. The growth rate of fungi is very slow and quite difficult to identify. A series of molecules with antifungal activity against different strains of fungi have been found in insects, which can be of great importance to tackle human diseases. Insects secrete such compounds, which can be peptides, as a part of their immune defense reactions. Active antifungal peptides developed by insects to rapidly eliminate infectious pathogens are considered a component of the defense munitions. This review focuses on naturally occurring antifungal peptides from insects and their challenges to be used as armaments against human diseases.

  6. First report of an antifungal amidase from Peltophorum pterocarpum. [corrected].

    PubMed

    Lam, Sze Kwan; Ng, Tzi Bun

    2010-05-01

    A 60 kDa antifungal amidase was purified from Peltophorum pterocarpum [corrected] seeds using an isolation procedure that entailed ion-exchange chromatography on Q-Sepharose, ion-exchange chromatography on DEAE-cellulose and FPLC-gel filtration on Superdex 75. Unlike most other antifungal proteins isolated previously, it was adsorbed on Q-Sepharose and DEAE-cellulose. The isolated protein, designated as peltopterin, exhibited an N-terminal amino acid sequence closely resembling those of amidases. It exhibited amidase activity and digested iodoacetamide with an optimum pH and temperature at pH 9 and 50 degrees C, respectively. It also hydrolyzed acrylamide and urea. It impeded mycelial growth in Rhizotonia solani with an IC(50) of 0.65 microm. Chitin deposition at hyphal tips in R. solani was observed by staining with Congo red after incubation with peltopterin. Its antifungal activity was stable throughout pH 0-14 and 25-100 degrees C. It potently inhibited HIV-1 reverse transcriptase with an IC(50) of 27 nm. PMID:19688818

  7. Antifungal defensins and their role in plant defense.

    PubMed

    Lacerda, Ariane F; Vasconcelos, Erico A R; Pelegrini, Patrícia Barbosa; Grossi de Sa, Maria F

    2014-01-01

    Since the beginning of the 90s lots of cationic plant, cysteine-rich antimicrobial peptides (AMP) have been studied. However, Broekaert et al. (1995) only coined the term "plant defensin," after comparison of a new class of plant antifungal peptides with known insect defensins. From there, many plant defensins have been reported and studies on this class of peptides encompass its activity toward microorganisms and molecular features of the mechanism of action against bacteria and fungi. Plant defensins also have been tested as biotechnological tools to improve crop production through fungi resistance generation in organisms genetically modified (OGM). Its low effective concentration towards fungi, ranging from 0.1 to 10 μM and its safety to mammals and birds makes them a better choice, in place of chemicals, to control fungi infection on crop fields. Herein, is a review of the history of plant defensins since their discovery at the beginning of 90s, following the advances on its structure conformation and mechanism of action towards microorganisms is reported. This review also points out some important topics, including: (i) the most studied plant defensins and their fungal targets; (ii) the molecular features of plant defensins and their relation with antifungal activity; (iii) the possibility of using plant defensin(s) genes to generate fungi resistant GM crops and biofungicides; and (iv) a brief discussion about the absence of products in the market containing plant antifungal defensins. PMID:24765086

  8. Design, Synthesis, and Antifungal Activity of New α-Aminophosphonates

    PubMed Central

    Rezaei, Zahra; Khabnadideh, Soghra; Zomorodian, Kamiar; Pakshir, Keyvan; Nadali, Setareh; Mohtashami, Nadia; Faghih Mirzaei, Ehsan

    2011-01-01

    α-Aminophosphonates are bioisosteres of amino acids and have several pharmacological activities. These compounds have been synthesized by various routes from reaction between amine, aldehyde, and phosphite compounds. In order to synthesize α-aminophosphonates, catalytic effect of CuCl2 was compared with FeCl3. Also all designed structures as well as griseofulvin were docked into the active site of microtubule (1JFF), using Autodock program. The results showed that the reactions were carried out in the presence of CuCl2 in lower yields, and also the time of reaction was longer in comparison with FeCl3. The chemical structures of the new compounds were confirmed by spectral analyses. The compounds were investigated for antifungal activity against several fungi in comparison with griseofulvin. An indole-derived bis(α-aminophosphonates) with the best negative ΔG in docking study showed maximum antifungal activity against Microsporum canis, and other investigated compounds did not have a good antifungal activity. PMID:25954522

  9. Antifungal activity of topical microemulsion containing a thiophene derivative

    PubMed Central

    Guimarães, Geovani Pereira; de Freitas Araújo Reis, Mysrayn Yargo; da Silva, Dayanne Tomaz Casimiro; Junior, Francisco Jaime Bezerra Mendonça; Converti, Attílio; Pessoa, Adalberto; de Lima Damasceno, Bolívar Ponciano Goulart; da Silva, José Alexsandro

    2014-01-01

    Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05) embedded in a microemulsion (ME). The minimum inhibitory concentration (MIC) was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05) showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270–540 μg.mL−1) and good activity against C. neoformans (MIC = 17 μg.mL−1). Candida species were susceptible to ME-5CN05 (70–140 μg.mL−1), but C. neoformans was much more, presenting a MIC value of 2.2 μg.mL−1. The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans. PMID:25242940

  10. Antifungal and cytotoxic activities of Nannorrhops ritchiana roots extract.

    PubMed

    Rashid, Rehana; Mukhtar, Farah; Khan, Abida

    2014-01-01

    This atudy was designed to evaluate the antifungal and cytotoxic activities of the Nannorrhops ritchiana (Mazari Palm) 80% methanol extract (NR-M) and its four crude extracts i.e., petroleum ether (NR-A), dichloromethane (NR-B), ethyl acetate (NR-C) and butanol (NR-D). The antifungal activity was determined by agar tube dilution method against nine fungal strains; Aspergillus flavus, Trichophyton longifusis, Trichophyton mentagrophytes, Aspergillus flavus and Microsporum canis were susceptible to the extracts with percentage inhibition of (70-80%). Extracts exhibited significant and good antifungal activity against various fungal strains. The results were deduced by comparing with those for miconazole, amphotericin B and ketoconazole as standard drugs. The fractions of methanolic extract were assayed for their brine shrimp cytotoxic activity. They exhibited low toxicity with LC50 values ranging from 285.7 to 4350.75 μg/mL at the concentration of obtained results warrant follow up through bioassay guided isolation of the active principles, future antiinfectious research. PMID:25362807

  11. Pyridine-grafted chitosan derivative as an antifungal agent.

    PubMed

    Jia, Ruixiu; Duan, Yunfei; Fang, Qiang; Wang, Xiangyang; Huang, Jianying

    2016-04-01

    Pyridine moieties were introduced into chitosan by nucleophilic substitution to afford N-(1-carboxybutyl-4-pyridinium) chitosan chloride (pyridine chitosan). The resulting chitosan derivative was well characterized, and its antifungal activity was examined, based on the inhibition of mycelial growth and spore germination. The results indicated that pyridine chitosan exhibited enhanced antifungal activity by comparison with pristine chitosan. The values of the minimum inhibitory concentration and the minimal fungicidal concentration of pyridine chitosan against Fulvia fulva were 0.13 mg/ml and 1 mg/ml, respectively, while the corresponding values against Botrytis cinerea were 0.13 mg/ml and 4 mg/ml, respectively. Severe morphological changes of pyridine chitosan-treated B. cinerea were observed, indicative that pyridine chitosan could damage and deform the structure of fungal hyphae and subsequently inhibit strain growth. Non-toxicity of pyridine chitosan was demonstrated by an acute toxicity study. These results are beneficial for assessing the potential utilization of this chitosan derivative and for exploring new functional antifungal agents with chitosan in the food industry. PMID:26593505

  12. Synthesis and biological evaluation of hydrazone derivatives as antifungal agents.

    PubMed

    Casanova, Bruna B; Muniz, Mauro N; de Oliveira, Thayse; de Oliveira, Luís Flavio; Machado, Michel M; Fuentefria, Alexandre M; Gosmann, Grace; Gnoatto, Simone C B

    2015-05-20

    Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16-32 μg/mL and 8-16 μg/mL, respectively. The compounds' action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents.

  13. Antifungal activity of Artemisia annua endophyte cultures against phytopathogenic fungi.

    PubMed

    Liu, C H; Zou, W X; Lu, H; Tan, R X

    2001-07-12

    Artemisia annua, well recognized for its production of antimalarial drug artemisinin, is seldom attacked by any of phytopathogenic fungi, which could be partially associated with the presence of endophytes. Present investigation is aiming at disclosing whether the endophytes inside A. annua produce antifungal substances. A total of 39 endophytes were isolated and fermented, and the ferment broth was evaluated in vitro for the antifungal activity against crop-threatening fungi Gaeumannomyces graminis var. tritici, Rhizoctonia cerealis, Helminthosporium sativum, Fusarium graminearum, Gerlachia nivalis and Phytophthora capsici. These plant pathogens are still causing wheat take-all, sharp eyespot, common rot, scab, snow mould, and pepper phytophthora blight, respectively. Out of 39 endophytes investigated, 21 can produce in vitro substances that are inhibitory to all or a few of the tested phytopathogens whereas the rest yielded nothing active. Moreover, the most active broth of endophyte IV403 was extracted with EtOAc and n-butanol, and comparisons of the antifungal activity of the extracts indicated that the major active metabolites were EtOAc-extractable.

  14. Antifungal activities and chemical composition of some medicinal plants.

    PubMed

    Mohammadi, A; Nazari, H; Imani, S; Amrollahi, H

    2014-06-01

    The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists and natural-products scientists are combing the earth for phytochemicals and leads, which could be developed for treatment of infectious diseases. The aim of this study was to investigate the antifungal activities of the essential oils of some medicinal plants such as Stachys pubescens, Thymus kotschyanus, Thymus daenensis and Bupleurum falcatum against Fusarium oxysporum, Aspergillus flavus and Alternaria alternata. The essential oils were used to evaluate their MICs and MFCs compared to the amphotricin B as a standard drug. The essential oils were also analyzed by GC/MS. Essential oils isolated from the S. pubescens, T. kotschyanus and B. falcatum showed strong antifungal activities. The essential oil of T. daenensis exhibited a moderate activity against the selected fungi in comparison with the other plants' essential oils. In addition, the results showed that 26, 23, 22 and 15 components were identified from the essential oils of T. kotschyanus, S. pubescens, T. daenensis and B. falcatum, respectively. These oils exhibited a noticeable antifungal activity against the selected fungi. Regarding obtained results and that natural antimicrobial substances are inexpensive and have fewer side effects, they convey potential for implementation in fungal pathogenic systems.

  15. Innovative phytosynthesized silver nanoarchitectures with enhanced antifungal and antioxidant properties

    NASA Astrophysics Data System (ADS)

    Ortan, Alina; Fierascu, Irina; Ungureanu, Camelia; Fierascu, Radu Claudiu; Avramescu, Sorin Marius; Dumitrescu, Ovidiu; Dinu-Pirvu, Cristina Elena

    2015-12-01

    While in the early era of nanotechnology, nanoparticles of noble metals were obtained through expensive methods, using toxic chemical reagents, in the last decade attempts are made to obtain the desired chemical composition, size, morphology, and other properties by eco and green synthesis, using plants. The aim of this paper is to compare two extraction methods (hydroalcoholic extraction and microwave extraction) used to phytosynthesize silver nanoparticles, in terms of nanoparticle (NP) morphology, antioxidant, and antifungal action, using an European native plant, Anthriscus cerefolium (L.) Hoffm. The extracts and the obtained NPs were characterized by modern analytical techniques (GC-MS, UV-Vis, SEM, TEM) and by phytochemical assays (total flavonoids, total terpenoids and total phenolic content). The antifungal activity (evaluated using the Kirby-Bauer method, against Aspergillus niger and Penicillium hirsutum) and the antioxidant activity (determined by the DPPH assay and a chemiluminescence assay) revealed notable differences between the samples, differences due to the extraction procedure followed. Also, preliminary studies regarding the stability and the toxicity of the nanoparticles are presented. By using the microwave-assisted extraction, not only smaller particles (less than 10 nm) were obtained, but also with better antifungal and antioxidant properties than the ones obtained by classical extraction.

  16. Antifungal Properties of Chenopodium ambrosioides Essential Oil Against Candida Species

    PubMed Central

    Chekem, Marie Stéphanie Goka; Lunga, Paul Keilah; Tamokou, Jean De Dieu; Kuiate, Jules Roger; Tane, Pierre; Vilarem, Gerard; Cerny, Muriel

    2010-01-01

    The essential oil of the aerial part (leaves, flowers and stem) of Chenopodium ambrosioides was obtained by hydrodistillation and its chemical composition analyzed by GC and GC/MS, which permitted the identification of 14 components, representing 98.8% of the total oil. Major components were α-terpinene (51.3%), p-cymene (23.4%) and p-mentha-1,8-diène (15.3%). The antifungal properties of this essential oil were investigated in vitro by the well diffusion and broth microdilution methods. The in vitro antifungal activity was concentration dependent and minimum inhibitory concentration values varied from 0.25 to 2 mg/mL. The in vivo antifungal activity was evaluated on an induced vaginal candidiasis rat model. The in vivo activity of the oil on mice vaginal candidiasis was not dose-dependent. Indeed, all the three tested doses; 0.1%, 1% and 10% led to the recovery of mice from the induced infection after 12 days of treatment. The effect of the essential oil on C. albicans ATCC 1663 fatty acid profile was studied. This oil has a relatively important dose-dependent effect on the fatty acids profile. PMID:27713382

  17. Antifungal activities and chemical composition of some medicinal plants.

    PubMed

    Mohammadi, A; Nazari, H; Imani, S; Amrollahi, H

    2014-06-01

    The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists and natural-products scientists are combing the earth for phytochemicals and leads, which could be developed for treatment of infectious diseases. The aim of this study was to investigate the antifungal activities of the essential oils of some medicinal plants such as Stachys pubescens, Thymus kotschyanus, Thymus daenensis and Bupleurum falcatum against Fusarium oxysporum, Aspergillus flavus and Alternaria alternata. The essential oils were used to evaluate their MICs and MFCs compared to the amphotricin B as a standard drug. The essential oils were also analyzed by GC/MS. Essential oils isolated from the S. pubescens, T. kotschyanus and B. falcatum showed strong antifungal activities. The essential oil of T. daenensis exhibited a moderate activity against the selected fungi in comparison with the other plants' essential oils. In addition, the results showed that 26, 23, 22 and 15 components were identified from the essential oils of T. kotschyanus, S. pubescens, T. daenensis and B. falcatum, respectively. These oils exhibited a noticeable antifungal activity against the selected fungi. Regarding obtained results and that natural antimicrobial substances are inexpensive and have fewer side effects, they convey potential for implementation in fungal pathogenic systems. PMID:24768063

  18. An overview of antifungal peptides derived from insect.

    PubMed

    Faruck, Mohammad Omer; Yusof, Faridah; Chowdhury, Silvia

    2016-06-01

    Fungi are not classified as plants or animals. They resemble plants in many ways but do not produce chlorophyll or make their own food photosynthetically like plants. Fungi are useful for the production of beer, bread, medicine, etc. More complex than viruses or bacteria; fungi can be destructive human pathogens responsible for various diseases in humans. Most people have a strong natural immunity against fungal infection. However, fungi can cause diseases when this immunity breaks down. In the last few years, fungal infection has increased strikingly and has been accompanied by a rise in the number of deaths of cancer patients, transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients owing to fungal infections. The growth rate of fungi is very slow and quite difficult to identify. A series of molecules with antifungal activity against different strains of fungi have been found in insects, which can be of great importance to tackle human diseases. Insects secrete such compounds, which can be peptides, as a part of their immune defense reactions. Active antifungal peptides developed by insects to rapidly eliminate infectious pathogens are considered a component of the defense munitions. This review focuses on naturally occurring antifungal peptides from insects and their challenges to be used as armaments against human diseases. PMID:26093218

  19. Antifungal and Antibacterial Metabolites from a French Poplar Type Propolis

    PubMed Central

    Boisard, Séverine; Le Ray, Anne-Marie; Landreau, Anne; Kempf, Marie; Cassisa, Viviane; Flurin, Catherine; Richomme, Pascal

    2015-01-01

    During this study, the in vitro antifungal and antibacterial activities of different extracts (aqueous and organic) obtained from a French propolis batch were evaluated. Antifungal activity was evaluated by broth microdilution on three pathogenic strains: Candida albicans, C. glabrata, and Aspergillus fumigatus. Antibacterial activity was assayed using agar dilution method on 36 Gram-negative and Gram-positive strains including Staphylococcus aureus. Organic extracts showed a significant antifungal activity against C. albicans and C. glabrata (MIC80 between 16 and 31 µg/mL) but only a weak activity towards A. fumigatus (MIC80 = 250 µg/mL). DCM based extracts exhibited a selective Gram-positive antibacterial activity, especially against S. aureus (SA) and several of its methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains (MIC100 30–97 µg/mL). A new and active derivative of catechin was also identified whereas a synergistic antimicrobial effect was noticed during this study. PMID:25873978

  20. Pyridine-grafted chitosan derivative as an antifungal agent.

    PubMed

    Jia, Ruixiu; Duan, Yunfei; Fang, Qiang; Wang, Xiangyang; Huang, Jianying

    2016-04-01

    Pyridine moieties were introduced into chitosan by nucleophilic substitution to afford N-(1-carboxybutyl-4-pyridinium) chitosan chloride (pyridine chitosan). The resulting chitosan derivative was well characterized, and its antifungal activity was examined, based on the inhibition of mycelial growth and spore germination. The results indicated that pyridine chitosan exhibited enhanced antifungal activity by comparison with pristine chitosan. The values of the minimum inhibitory concentration and the minimal fungicidal concentration of pyridine chitosan against Fulvia fulva were 0.13 mg/ml and 1 mg/ml, respectively, while the corresponding values against Botrytis cinerea were 0.13 mg/ml and 4 mg/ml, respectively. Severe morphological changes of pyridine chitosan-treated B. cinerea were observed, indicative that pyridine chitosan could damage and deform the structure of fungal hyphae and subsequently inhibit strain growth. Non-toxicity of pyridine chitosan was demonstrated by an acute toxicity study. These results are beneficial for assessing the potential utilization of this chitosan derivative and for exploring new functional antifungal agents with chitosan in the food industry.

  1. Clinically relevant drug-drug interactions between antiretrovirals and antifungals

    PubMed Central

    Vadlapatla, Ramya Krishna; Patel, Mitesh; Paturi, Durga K; Pal, Dhananjay; Mitra, Ashim K

    2015-01-01

    Introduction Complete delineation of the HIV-1 life cycle has resulted in the development of several antiretroviral drugs. Twenty-five therapeutic agents belonging to five different classes are currently available for the treatment of HIV-1 infections. Advent of triple combination antiretroviral therapy has significantly lowered the mortality rate in HIV patients. However, fungal infections still represent major opportunistic diseases in immunocompromised patients worldwide. Areas covered Antiretroviral drugs that target enzymes and/or proteins indispensable for viral replication are discussed in this article. Fungal infections, causative organisms, epidemiology and preferred treatment modalities are also outlined. Finally, observed/predicted drug-drug interactions between antiretrovirals and antifungals are summarized along with clinical recommendations. Expert opinion Concomitant use of amphotericin B and tenofovir must be closely monitored for renal functioning. Due to relatively weak interactive potential with the CYP450 system, fluconazole is the preferred antifungal drug. High itraconazole doses (> 200 mg/day) are not advised in patients receiving booster protease inhibitor (PI) regimen. Posaconazole is contraindicated in combination with either efavirenz or fosamprenavir. Moreover, voriconazole is contraindicated with high-dose ritonavir-boosted PI. Echino-candins may aid in overcoming the limitations of existing antifungal therapy. An increasing number of documented or predicted drug-drug interactions and therapeutic drug monitoring may aid in the management of HIV-associated opportunistic fungal infections. PMID:24521092

  2. Cytocompatible antifungal acrylic resin containing silver nanoparticles for dentures

    PubMed Central

    Acosta-Torres, Laura Susana; Mendieta, Irasema; Nuñez-Anita, Rosa Elvira; Cajero-Juárez, Marcos; Castaño, Víctor M

    2012-01-01

    Background Inhibition of Candida albicans on denture resins could play a significant role in preventing the development of denture stomatitis. The safety of a new dental material with antifungal properties was analyzed in this work. Methods Poly(methyl methacrylate) [PMMA] discs and PMMA-silver nanoparticle discs were formulated, with the commercial acrylic resin, Nature-CrylTM, used as a control. Silver nanoparticles were synthesized and characterized by ultraviolet-visible spectroscopy, dispersive Raman spectroscopy, and transmission electron microscopy. The antifungal effect was assessed using a luminescent microbial cell viability assay. Biocompatibility tests were carried out using NIH-3T3 mouse embryonic fibroblasts and a Jurkat human lymphocyte cell line. Cells were cultured for 24 or 72 hours in the presence or absence of the polymer formulations and analyzed using three different tests, ie, cellular viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell proliferation by enzyme-linked immunosorbent assay BrdU, and genomic DNA damage (Comet assay). Finally, the samples were evaluated mechanically, and the polymer-bearing silver nanoparticles were analyzed microscopically to evaluate dispersion of the nanoparticles. Results The results show that PMMA-silver nanoparticle discs significantly reduce adherence of C. albicans and do not affect metabolism or proliferation. They also appear not to cause genotoxic damage to cells. Conclusion The present work has developed a new biocompatible antifungal PMMA denture base material. PMID:22969297

  3. Antifungal defensins and their role in plant defense

    PubMed Central

    Lacerda, Ariane F.; Vasconcelos, Érico A. R.; Pelegrini, Patrícia Barbosa; Grossi de Sa, Maria F.

    2014-01-01

    Since the beginning of the 90s lots of cationic plant, cysteine-rich antimicrobial peptides (AMP) have been studied. However, Broekaert et al. (1995) only coined the term “plant defensin,” after comparison of a new class of plant antifungal peptides with known insect defensins. From there, many plant defensins have been reported and studies on this class of peptides encompass its activity toward microorganisms and molecular features of the mechanism of action against bacteria and fungi. Plant defensins also have been tested as biotechnological tools to improve crop production through fungi resistance generation in organisms genetically modified (OGM). Its low effective concentration towards fungi, ranging from 0.1 to 10 μM and its safety to mammals and birds makes them a better choice, in place of chemicals, to control fungi infection on crop fields. Herein, is a review of the history of plant defensins since their discovery at the beginning of 90s, following the advances on its structure conformation and mechanism of action towards microorganisms is reported. This review also points out some important topics, including: (i) the most studied plant defensins and their fungal targets; (ii) the molecular features of plant defensins and their relation with antifungal activity; (iii) the possibility of using plant defensin(s) genes to generate fungi resistant GM crops and biofungicides; and (iv) a brief discussion about the absence of products in the market containing plant antifungal defensins. PMID:24765086

  4. Antifungal defensins and their role in plant defense.

    PubMed

    Lacerda, Ariane F; Vasconcelos, Erico A R; Pelegrini, Patrícia Barbosa; Grossi de Sa, Maria F

    2014-01-01

    Since the beginning of the 90s lots of cationic plant, cysteine-rich antimicrobial peptides (AMP) have been studied. However, Broekaert et al. (1995) only coined the term "plant defensin," after comparison of a new class of plant antifungal peptides with known insect defensins. From there, many plant defensins have been reported and studies on this class of peptides encompass its activity toward microorganisms and molecular features of the mechanism of action against bacteria and fungi. Plant defensins also have been tested as biotechnological tools to improve crop production through fungi resistance generation in organisms genetically modified (OGM). Its low effective concentration towards fungi, ranging from 0.1 to 10 μM and its safety to mammals and birds makes them a better choice, in place of chemicals, to control fungi infection on crop fields. Herein, is a review of the history of plant defensins since their discovery at the beginning of 90s, following the advances on its structure conformation and mechanism of action towards microorganisms is reported. This review also points out some important topics, including: (i) the most studied plant defensins and their fungal targets; (ii) the molecular features of plant defensins and their relation with antifungal activity; (iii) the possibility of using plant defensin(s) genes to generate fungi resistant GM crops and biofungicides; and (iv) a brief discussion about the absence of products in the market containing plant antifungal defensins.

  5. Ibuprofen potentiates the in vivo antifungal activity of fluconazole against Candida albicans murine infection.

    PubMed

    Costa-de-Oliveira, Sofia; Miranda, Isabel M; Silva-Dias, Ana; Silva, Ana P; Rodrigues, Acácio G; Pina-Vaz, Cidália

    2015-07-01

    Candida albicans is the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression.

  6. Ibuprofen Potentiates the In Vivo Antifungal Activity of Fluconazole against Candida albicans Murine Infection

    PubMed Central

    Miranda, Isabel M.; Silva-Dias, Ana; Silva, Ana P.; Rodrigues, Acácio G.; Pina-Vaz, Cidália

    2015-01-01

    Candida albicans is the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression. PMID:25845879

  7. Antifungal susceptibility patterns of a global collection of fungal isolates: results of the SENTRY Antifungal Surveillance Program (2013).

    PubMed

    Castanheira, Mariana; Messer, Shawn A; Rhomberg, Paul R; Pfaller, Michael A

    2016-06-01

    Among 1846 fungal clinical isolates from 31 countries, echinocandin resistance in Candida spp. ranged from 0.0% to 2.8% (highest for anidulafungin versus Candida glabrata), and fluconazole resistance was noted among 11.9% and 11.6% of the C. glabrata and Candida tropicalis, respectively. Two isolates of Aspergillus fumigatus displayed elevated MICs for itraconazole and carried cyp51a mutations encoding TR34 L98H. All Cryptococcus neoformans had azole MIC values below epidemiological cutoff values. The increasing resistance among certain species and more frequent reports of breakthrough infections in patients undergoing antifungal therapy highlights the importance of antifungal surveillance to guide therapy for patients with invasive fungal infections. PMID:27061369

  8. Identification and characterization of the antifungal substances of a novel Streptomyces cavourensis NA4.

    PubMed

    Pan, Hua-Qi; Yu, Su-Ya; Song, Chun-Feng; Wang, Nan; Hua, Hui-Ming; Hu, Jiang-Chun; Wang, Shu-Jin

    2015-03-01

    A new actinomycete strain NA4 was isolated from a deep-sea sediment collected from the South China Sea and showed promising antifungal activities against soilborne fungal pathogens. It was identified as Streptomyces cavourensis by morphological, physiological, and phylogenetic analyses based on its 16S rRNA gene sequence. The main antifungal components were isolated and identified from the fermentation culture as bafilomycins B1 and C1. These compounds exhibited significant antifungal activities and a broad antifungal spectrum. The results suggest that the Streptomyces cavourensis NA4 and bafilomycins B1 and C1 could be used as potential biocontrol agents for soilborne fungal diseases of plants.

  9. Diversity and antifungal susceptibility of Norwegian Candida glabrata clinical isolates

    PubMed Central

    Andersen, Kari-Mette; Kristoffersen, Anne Karin; Ingebretsen, André; Vikholt, Katharina Johnsen; Örtengren, Ulf Thore; Olsen, Ingar; Enersen, Morten; Gaustad, Peter

    2016-01-01

    Background Increasing numbers of immunocompromised patients have resulted in greater incidence of invasive fungal infections with high mortality. Candida albicans infections dominate, but during the last decade, Candida glabrata has become the second highest cause of candidemia in the United States and Northern Europe. Reliable and early diagnosis, together with appropriate choice of antifungal treatment, is needed to combat these challenging infections. Objectives To confirm the identity of 183 Candida glabrata isolates from different human body sites using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and VITEK®2, and to analyze isolate protein profiles and antifungal susceptibility. The minimum inhibitory concentration (MIC) of seven antifungal drugs was determined for the isolates to elucidate susceptibility. Design A total of 183 C. glabrata isolates obtained between 2002 and 2012 from Norwegian health-care units were analyzed. For species verification and differentiation, biochemical characterization (VITEK®2) and mass spectrometry (MALDI–TOF) were used. MIC determination for seven antifungal drugs was undertaken using E-tests®. Results Using VITEK®2, 92.9% of isolates were identified as C. glabrata, while all isolates (100%) were identified as C. glabrata using MALDI-TOF. Variation in protein spectra occurred for all identified C. glabrata isolates. The majority of isolates had low MICs to amphotericin B (≤1 mg/L for 99.5%) and anidulafungin (≤0.06 mg/L for 98.9%). For fluconazole, 18% of isolates had MICs >32 mg/L and 82% had MICs in the range ≥0.016 mg/L to ≤32 mg/L. Conclusions Protein profiles and antifungal susceptibility characteristics of the C. glabrata isolates were diverse. Clustering of protein profiles indicated that many azole resistant isolates were closely related. In most cases, isolates had highest susceptibility to amphotericin B and anidulafungin. The results confirmed previous observations of high

  10. Antifungal activities of three different Lactobacillus species and their production of antifungal carboxylic acids in wheat sourdough.

    PubMed

    Axel, Claudia; Brosnan, Brid; Zannini, Emanuele; Peyer, Lorenzo C; Furey, Ambrose; Coffey, Aidan; Arendt, Elke K

    2016-02-01

    This study was undertaken to assess the antifungal performance of three different Lactobacillus species.Experiments were conducted in vitro and in situ to extend the shelf life of wheat bread. Standard sourdough analyses were performed characterising acidity and carbohydrate levels. Overall, the strains showed good inhibition in vitro against the indicator mould Fusarium culmorum TMW4.2043. Sourdough bread fermented with Lactobacillus amylovorus DSM19280 performed best in the in situ shelf life experiment. An average shelf life extension of six more mould-free days was reached when compared to the non-acidified control bread. A range of antifungal-active acids like 3-phenyllactic acid, 4-hydroxyphenyllactic acid and 2-hydroxyisocaproic acid in quantities between 0.1 and 360 mg/kg were present in the freeze-dried sourdoughs. Their concentration differed greatly amongst the species.However, a higher concentration of these compounds could not completely justify the growth inhibition of environmental moulds. In particular, although Lb. reuteri R29 produced the highest total concentration of these active compounds in the sourdough, its addition to bread did not result in a longest shelf life. Nevertheless, when the artificial compounds were spiked into a chemically acidified dough, it succeeded in a longer shelf life (+25 %) than achieved only by acidifying the dough. This provides evidence of their contribution to the antifungal activity and their synergy in concentration levels far below their single minimal inhibition concentrations under acidic conditions.

  11. Polyglycolic acid microneedles modified with inkjet-deposited antifungal coatings.

    PubMed

    Boehm, Ryan D; Daniels, Justin; Stafslien, Shane; Nasir, Adnan; Lefebvre, Joe; Narayan, Roger J

    2015-01-01

    In this study, the authors examined use of piezoelectric inkjet printing to apply an antifungal agent, voriconazole, to the surfaces of biodegradable polyglycolic acid microneedles. Polyglycolic acid microneedles with sharp tips (average tip radius = 25 ± 3 μm) were prepared using a combination of injection molding and drawing lithography. The elastic modulus (9.9 ± 0.3 GPa) and hardness (588.2 ± 33.8 MPa) values of the polyglycolic acid material were determined using nanoindentation and were found to be suitable for use in transdermal drug delivery devices. Voriconazole was deposited onto the polyglycolic acid microneedles by means of piezoelectric inkjet printing. It should be noted that voriconazole has poor solubility in water; however, it is readily soluble in many organic solvents. Optical imaging, scanning electron microscopy, energy dispersive x-ray spectrometry, and Fourier transform infrared spectroscopy were utilized to examine the microneedle geometries and inkjet-deposited surface coatings. Furthermore, an in vitro agar plating study was performed on the unmodified, vehicle-modified, and voriconazole-modified microneedles. Unlike the unmodified and vehicle-modified microneedles, the voriconazole-modified microneedles showed antifungal activity against Candida albicans. The unmodified, vehicle-modified, and voriconazole-modified microneedles did not show activity against Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus. The results indicate that piezoelectric inkjet printing may be useful for loading transdermal drug delivery devices such as polyglycolic acid microneedles with antifungal pharmacologic agents and other pharmacologic agents with poor solubility in aqueous solutions.

  12. Polyglycolic acid microneedles modified with inkjet-deposited antifungal coatings.

    PubMed

    Boehm, Ryan D; Daniels, Justin; Stafslien, Shane; Nasir, Adnan; Lefebvre, Joe; Narayan, Roger J

    2015-01-01

    In this study, the authors examined use of piezoelectric inkjet printing to apply an antifungal agent, voriconazole, to the surfaces of biodegradable polyglycolic acid microneedles. Polyglycolic acid microneedles with sharp tips (average tip radius = 25 ± 3 μm) were prepared using a combination of injection molding and drawing lithography. The elastic modulus (9.9 ± 0.3 GPa) and hardness (588.2 ± 33.8 MPa) values of the polyglycolic acid material were determined using nanoindentation and were found to be suitable for use in transdermal drug delivery devices. Voriconazole was deposited onto the polyglycolic acid microneedles by means of piezoelectric inkjet printing. It should be noted that voriconazole has poor solubility in water; however, it is readily soluble in many organic solvents. Optical imaging, scanning electron microscopy, energy dispersive x-ray spectrometry, and Fourier transform infrared spectroscopy were utilized to examine the microneedle geometries and inkjet-deposited surface coatings. Furthermore, an in vitro agar plating study was performed on the unmodified, vehicle-modified, and voriconazole-modified microneedles. Unlike the unmodified and vehicle-modified microneedles, the voriconazole-modified microneedles showed antifungal activity against Candida albicans. The unmodified, vehicle-modified, and voriconazole-modified microneedles did not show activity against Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus. The results indicate that piezoelectric inkjet printing may be useful for loading transdermal drug delivery devices such as polyglycolic acid microneedles with antifungal pharmacologic agents and other pharmacologic agents with poor solubility in aqueous solutions. PMID:25732934

  13. Predictors of choice of initial antifungal treatment in intraabdominal candidiasis.

    PubMed

    Lagunes, L; Borgatta, B; Martín-Gomez, M T; Rey-Pérez, A; Antonelli, M; Righi, E; Merelli, M; Brugnaro, P; Dimopoulos, G; Garnacho-Montero, J; Colombo, A L; Luzzati, R; Menichetti, F; Muñoz, P; Nucci, M; Scotton, G; Viscoli, C; Tumbarello, M; Bassetti, M; Rello, J

    2016-08-01

    Intraabdominal candidiasis (IAC) is the second most frequent form of invasive candidiasis, and is associated with high mortality rates. This study aims to identify current practices in initial antifungal treatment (IAT) in a real-world scenario and to define the predictors of the choice of echinocandins or azoles in IAC episodes. Secondary analysis was performed of a multinational retrospective cohort at 13 teaching hospitals in four countries (Italy, Greece, Spain and Brazil), over a 3-year period (2011-2013). IAC was identified in 481 patients, 323 of whom received antifungal therapy (classified as the treatment group). After excluding 13 patients given amphotericin B, the treatment group was further divided into the echinocandin group (209 patients; 64.7%) and the azole group (101 patients; 32.3%). Median APACHE II scores were significantly higher in the echinocandin group (p 0.013), but IAT did not differ significantly with regard to the Candida species involved. Logistic multivariate stepwise regression analysis, adjusted for centre effect, identified septic shock (adjusted OR (aOR) 1.54), APACHE II >15 (aOR 1.16) and presence in surgical ward at diagnosis (aOR 1.16) as the top three independent variables associated with an empirical echinocandin regimen. No differences in 30-day mortality were observed between groups. Echinocandin regimen was the first choice for IAT in patients with IAC. No statistical differences in mortality were observed between regimens, but echinocandins were administered to patients with more severe disease. Some disagreements were identified between current clinical guidelines and prescription of antifungals for IAC at the bedside, so further educational measures are required to optimize therapies. PMID:27432766

  14. Time to Initiation of Antifungal Therapy for Neonatal Candidiasis

    PubMed Central

    Tran, Tu T.; Bui, Ivilynn; Wang, Mike K.; Vo, Andrew

    2013-01-01

    The effect of delayed antifungal therapy in critically ill infants with invasive candidiasis has not been studied. Our objective was to evaluate the effect of time to initiation of antifungal therapy (TIA) on mortality, disseminated disease, and postinfection hospital stay. We conducted a cohort study of critically ill infants with cultures positive for Candida from 1990 to 2008. TIA was defined as the number of hours from the collection of the first positive culture until the start of antifungal therapy. Of 96 infants, 57% were male, the median gestational age was 27 weeks (range, 23 to 41 weeks), and the median birth weight was 956 g (range, 415 to 6,191 g). Most subjects received amphotericin B deoxycholate. TIA was ≤24 h for 35% of infants, between 25 and 48 h for 42%, and >48 h for 23%. Eleven subjects died during hospitalization, and 22% had disseminated candidiasis. The median duration of hospital stay postinfection was 53 days (range, 6 to 217 days). Both univariate and multivariate analyses demonstrated that TIA was not associated with mortality, disseminated disease, or hospital stay postinfection. However, ventilator use for >60 days significantly increased the risk of death (odds ratio [OR], 9.5; 95% confidence interval [CI], 2.2 to 66.7; P = 0.002). Prolonged candidemia increased the risk of disseminated disease by 10% per day of positive culture (OR, 1.1; 95% CI, 1.08 to 1.2; P = 0.007), and low gestational age was associated with increased neonatal intensive care unit (NICU) stay after the first positive Candida culture by 0.94 weeks (95% CI, 0.70 to 0.98; P < 0.001). The TIA was not associated with all-cause mortality, disseminated candidiasis, and postinfection length of hospital stay. PMID:23507285

  15. Antifungal Therapy in Hematopoietic Stem Cell Transplant Recipients.

    PubMed

    Busca, Alessandro; Pagano, Livio

    2016-01-01

    Invasive fungal infections (IFI) represent a major hindrance to the success of hematopoietic stem cell transplantation (HSCT), contributing substantially to morbidity and infection-related mortality. During the most recent years several reports indicate an overall increase of IFI among hematologic patients, in particular, invasive aspergillosis, that may be explained, at least partially, by the fact that diagnoses only suspected in the past, are now more easily established due to the application of serum biomarkers and early use of CT scan. Along with new diagnostic options, comes the recent development of novel antifungal agents that expanded the spectrum of activity over traditional treatments contributing to the successful management of fungal diseases. When introduced in 1959, Amphotericin B deoxycholate (d-AmB) was a life-saving drug, and the clinical experience over 50 years has proven that this compound is effective although toxic. Given the superior safety profile, lipid formulations of AmB have now replaced d-AmB in many circumstances. Similarly, echinocandins have been investigated as initial therapy for IA in several clinical trials including HSCT recipients, although the results were moderately disappointing leading to a lower grade of recommendation in the majority of published guidelines. Azoles represent the backbone of therapy for treating immunocompromised patients with IFI, including voriconazole and the newcomer isavuconazole; in addition, large studies support the use of mold-active azoles, namely voriconazole and posaconazole, as antifungal prophylaxis in HSCT recipients. The aim of the present review is to summarize the clinical application of antifungal agents most commonly employed in the treatment of IFI. PMID:27648202

  16. Antifungal activity of gold nanoparticles prepared by solvothermal method

    SciTech Connect

    Ahmad, Tokeer; Wani, Irshad A.; Lone, Irfan H.; Ganguly, Aparna; Manzoor, Nikhat; Ahmad, Aijaz; Ahmed, Jahangeer; Al-Shihri, Ayed S.

    2013-01-15

    Graphical abstract: Gold nanoparticles (7 and 15 nm) of very high surface area (329 and 269 m{sup 2}/g) have been successfully synthesized through solvothermal method by using tin chloride and sodium borohydride as reducing agents. As-prepared gold nanoparticles shows very excellent antifungal activity against Candida isolates and activity increases with decrease in the particle size. Display Omitted Highlights: ► Effect of reducing agents on the morphology of gold nanoparticles. ► Highly uniform and monodisperse gold nanoparticles (7 nm). ► Highest surface area of gold nanoparticles (329 m{sup 2/}g). ► Excellent antifungal activity of gold nanoparticles against Candida strains. -- Abstract: Gold nanoparticles have been successfully synthesized by solvothermal method using SnCl{sub 2} and NaBH{sub 4} as reducing agents. X-ray diffraction studies show highly crystalline and monophasic nature of the gold nanoparticles with face centred cubic structure. The transmission electron microscopic studies show the formation of nearly spherical gold nanoparticles of average size of 15 nm using SnCl{sub 2}, however, NaBH{sub 4} produced highly uniform, monodispersed and spherical gold nanoparticles of average grain size of 7 nm. A high surface area of 329 m{sup 2}/g for 7 nm and 269 m{sup 2}/g for 15 nm gold nanoparticles was observed. UV–vis studies assert the excitations over the visible region due to transverse and longitudinal surface plasmon modes. The gold nanoparticles exhibit excellent size dependant antifungal activity and greater biocidal action against Candida isolates for 7 nm sized gold nanoparticles restricting the transmembrane H{sup +} efflux of the Candida species than 15 nm sized gold nanoparticles.

  17. Antifungal Therapy in Hematopoietic Stem Cell Transplant Recipients

    PubMed Central

    Busca, Alessandro; Pagano, Livio

    2016-01-01

    Invasive fungal infections (IFI) represent a major hindrance to the success of hematopoietic stem cell transplantation (HSCT), contributing substantially to morbidity and infection-related mortality. During the most recent years several reports indicate an overall increase of IFI among hematologic patients, in particular, invasive aspergillosis, that may be explained, at least partially, by the fact that diagnoses only suspected in the past, are now more easily established due to the application of serum biomarkers and early use of CT scan. Along with new diagnostic options, comes the recent development of novel antifungal agents that expanded the spectrum of activity over traditional treatments contributing to the successful management of fungal diseases. When introduced in 1959, Amphotericin B deoxycholate (d-AmB) was a life-saving drug, and the clinical experience over 50 years has proven that this compound is effective although toxic. Given the superior safety profile, lipid formulations of AmB have now replaced d-AmB in many circumstances. Similarly, echinocandins have been investigated as initial therapy for IA in several clinical trials including HSCT recipients, although the results were moderately disappointing leading to a lower grade of recommendation in the majority of published guidelines. Azoles represent the backbone of therapy for treating immunocompromised patients with IFI, including voriconazole and the newcomer isavuconazole; in addition, large studies support the use of mold-active azoles, namely voriconazole and posaconazole, as antifungal prophylaxis in HSCT recipients. The aim of the present review is to summarize the clinical application of antifungal agents most commonly employed in the treatment of IFI.

  18. Antifungal Therapy in Hematopoietic Stem Cell Transplant Recipients

    PubMed Central

    Busca, Alessandro; Pagano, Livio

    2016-01-01

    Invasive fungal infections (IFI) represent a major hindrance to the success of hematopoietic stem cell transplantation (HSCT), contributing substantially to morbidity and infection-related mortality. During the most recent years several reports indicate an overall increase of IFI among hematologic patients, in particular, invasive aspergillosis, that may be explained, at least partially, by the fact that diagnoses only suspected in the past, are now more easily established due to the application of serum biomarkers and early use of CT scan. Along with new diagnostic options, comes the recent development of novel antifungal agents that expanded the spectrum of activity over traditional treatments contributing to the successful management of fungal diseases. When introduced in 1959, Amphotericin B deoxycholate (d-AmB) was a life-saving drug, and the clinical experience over 50 years has proven that this compound is effective although toxic. Given the superior safety profile, lipid formulations of AmB have now replaced d-AmB in many circumstances. Similarly, echinocandins have been investigated as initial therapy for IA in several clinical trials including HSCT recipients, although the results were moderately disappointing leading to a lower grade of recommendation in the majority of published guidelines. Azoles represent the backbone of therapy for treating immunocompromised patients with IFI, including voriconazole and the newcomer isavuconazole; in addition, large studies support the use of mold-active azoles, namely voriconazole and posaconazole, as antifungal prophylaxis in HSCT recipients. The aim of the present review is to summarize the clinical application of antifungal agents most commonly employed in the treatment of IFI. PMID:27648202

  19. Antifungal activity of topical microemulsion containing a thiophene derivative.

    PubMed

    Guimarães, Geovani Pereira; de Freitas Araújo Reis, Mysrayn Yargo; da Silva, Dayanne Tomaz Casimiro; Junior, Francisco Jaime Bezerra Mendonça; Converti, Attílio; Pessoa, Adalberto; de Lima Damasceno, Bolívar Ponciano Goulart; da Silva, José Alexsandro

    2014-01-01

    Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05) embedded in a microemulsion (ME). The minimum inhibitory concentration (MIC) was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05) showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270-540 μg . mL(-1)) and good activity against C. neoformans (MIC = 17 μg . mL(-1)). Candida species were susceptible to ME-5CN05 (70-140 μg . mL(-1)), but C. neoformans was much more, presenting a MIC value of 2.2 μg . mL(-1). The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans. PMID:25242940

  20. Antifungal activity of the essential oil from Calendula officinalis L. (asteraceae) growing in Brazil.

    PubMed

    Gazim, Zilda Cristiane; Rezende, Claudia Moraes; Fraga, Sandra Regina; Svidzinski, Terezinha Inez Estivaleti; Cortez, Diógenes Aparicio Garcia

    2008-01-01

    This study tested in vitro activity of the essential oil from flowers of Calendula officinalis using disk-diffusion techniques. The antifungal assay results showed for the first time that the essential oil has good potential antifungal activity: it was effective against all 23 clinical fungi strains tested. PMID:24031180

  1. Antifungal compounds from turmeric and nutmeg with activity against plant pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The antifungal activity of twenty-two common spices was evaluated against plant pathogens using direct-bioautography coupled Colletotrichum bioassays. Turmeric, nutmeg, ginger, clove, oregano, cinnamon, anise, fennel, basil, black cumin, and black pepper showed antifungal activity against the plant ...

  2. Optimization of Spore and Antifungal Lipopeptide Production during the Solid State Fermentation of Bacillus subtilis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacillus subtilis strain TrigoCor 1448 was grown on wheat middlings in 0.5-liter solid state fermentation (SSF) bioreactors for the production of an antifungal biological control agent. Total antifungal activity was quantified using a 96-well microplate bioassay against the plant pathogen Fusarium ...

  3. Augmenting antifungal activity of oxidizing agent with kojic acid: Control of Penicillium strains infecting crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative treatment is a strategy for preventing Penicillium contamination in foods or crops. Antifungal efficacy of oxidant [hydrogen peroxide (H2O2)], biotic effector [kojic acid (KA)] and abiotic stress (heat), alone or in combination, was investigated in Penicillium. The levels of antifungal int...

  4. Development of a novel in vitro onychomycosis model for the evaluation of topical antifungal activity.

    PubMed

    Sleven, Reindert; Lanckacker, Ellen; Boulet, Gaëlle; Delputte, Peter; Maes, Louis; Cos, Paul

    2015-05-01

    A novel in vitro onychomycosis model was developed to easily predict the topical activity potential of novel antifungal drugs. The model encompasses drug activity and diffusion through bovine hoof slices in a single experimental set-up. Results correspond well with the antifungal susceptibility assay and Franz cell diffusion test.

  5. Some Antifungal Properties of Sorbic Acid Extracted from Berries of Rowan (Sorbus Aucuparia).

    ERIC Educational Resources Information Center

    Brunner, Ulrich

    1985-01-01

    The food preservative sorbic acid can be extracted from Eurasian mountain ash berries (commercially available) and used to show antifungal properties in microbiological investigations. Techniques for extraction, purification, ultraviolet analysis, and experiments displaying antifungal activity are described. A systematic search for similar…

  6. In Vitro Activities of 35 Double Combinations of Antifungal Agents against Scedosporium apiospermum and Scedosporium prolificans▿

    PubMed Central

    Cuenca-Estrella, Manuel; Alastruey-Izquierdo, Ana; Alcazar-Fuoli, Laura; Bernal-Martinez, Leticia; Gomez-Lopez, Alicia; Buitrago, Maria J.; Mellado, Emilia; Rodriguez-Tudela, Juan L.

    2008-01-01

    Activities of 35 combinations of antifungal agents against Scedosporium spp. were analyzed by a checkerboard microdilution design and the summation of fractional concentration index. An average indifferent effect was detected apart from combinations of azole agents and echinocandins against Scedosporium apiospermum. Antagonism was absent for all antifungal combinations against both species. PMID:18195067

  7. Purification and characterization of antifungal compounds from Lactobacillus plantarum HD1 isolated from kimchi.

    PubMed

    Ryu, Eun Hye; Yang, Eun Ju; Woo, Eun Rhan; Chang, Hae Choon

    2014-08-01

    Strain HD1 with antifungal activity was isolated from kimchi and identified as Lactobacillus plantarum. Antifungal compounds from Lb. plantarum HD1 were active against food- and feed-borne filamentous fungi and yeasts in a spot-on-the-lawn assay. Antifungal activity of Lb. plantarum HD1 was stronger against filamentous fungi than yeast. Antifungal compounds were purified using solid phase extraction (SPE) and recycling preparative-HPLC. Structures of the antifungal compounds were elucidated by electrospray ionization-mass spectrometry and nuclear magnetic resonance. Active compounds from Lb. plantarum HD1 were identified as 5-oxododecanoic acid (MW 214), 3-hydroxy decanoic acid (MW 188), and 3-hydroxy-5-dodecenoic acid (MW 214). To investigate the potential application of these antifungal compounds for reduction of fungal spoilage in foods, Korean draft rice wine was used as a food model. White film-forming yeasts were observed in control draft rice wine after 11 days of incubation. However, film-forming yeasts were not observed in draft rice wine treated with SPE-prepared culture supernatant of Lb. plantarum HD1 (equivalent to 2.5% addition of culture supernatant) until 27 days of incubation. The addition of antifungal compounds to Korean draft rice wine extended shelf-life up to 27 days at 10 °C without any sterilization process. Therefore, the antifungal activity of Lb. plantarum HD1 may lead to the development of powerful biopreservative systems capable of preventing food- and feed-borne fungal spoilage.

  8. Antifungal activities of Hedychium essential oils and plant extracts against mycotoxigenic fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant-derived antifungal compounds are preferred to chemicals to reduce the risk of toxic effects on humans, livestock and the environment. Essential oil extracted from rhizomes and plant extracts of ornamental ginger lily (Hedychium spp.) were evaluated for their antifungal activity against two fu...

  9. Antifungal activity of the essential oil from Calendula officinalis L. (asteraceae) growing in Brazil

    PubMed Central

    Gazim, Zilda Cristiane; Rezende, Claudia Moraes; Fraga, Sandra Regina; Svidzinski, Terezinha Inez Estivaleti; Cortez, Diógenes Aparicio Garcia

    2008-01-01

    This study tested in vitro activity of the essential oil from flowers of Calendula officinalis using disk-diffusion techniques. The antifungal assay results showed for the first time that the essential oil has good potential antifungal activity: it was effective against all 23 clinical fungi strains tested. PMID:24031180

  10. Antifungal, mosquito deterrent, and larvicidal activity of N-(benzylidene)-3-cyclohexylpropionic acid hydrazide derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydrazone derivatives possess good antifungal and insecticidal activities and their structure are used in pesticide design. In the present study, ten hydrazone derivatives (2a-j) were evaluated for their antifungal activity against Colletotrichum, Botrytis, Fusarium and Phomopsis species and for the...

  11. Local anaesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh.

    PubMed

    Dolara, P; Corte, B; Ghelardini, C; Pugliese, A M; Cerbai, E; Menichetti, S; Lo Nostro, A

    2000-05-01

    We extracted, purified and characterized 8 sesquiterpene fractions from Commyphora molmol. In particular, we focused our attention on a mixture of furanodiene-6-one and methoxyfuranoguaia-9-ene-8-one, which showed antibacterial and antifungal activity against standard pathogenic strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans, with minimum inhibitory concentrations ranging from 0.18 to 2.8 micrograms/ml. These compounds also had local anaesthetic activity, blocking the inward sodium current of excitable mammalian membranes. PMID:10865454

  12. Trichoharzianol, a new antifungal from Trichoderma harzianum F031.

    PubMed

    Jeerapong, Chotika; Phupong, Worrapong; Bangrak, Phuwadol; Intana, Warin; Tuchinda, Patoomratana

    2015-04-15

    A new decalin derivative, trichoharzianol (1), together with three known compounds, eujavanicol A (2), 5-hydroxy-3-hydroxymethyl-2-methyl-7-methoxychromone (3), and 4,6-dihydroxy-5-methylphthalide (4), were isolated from Trichoderma harzianum F031. For the first time, compounds 2-4 were reported from the Trichoderma species. Their structures were characterized by spectroscopic methods. Trichoharzianol (1) showed the highest antifungal activity against Colletotrichum gloeosporioides, with a minimum inhibitory concentration (MIC) of 128 μg/mL. PMID:25817439

  13. Antiviral, antifungal and antiprotozoal agents in the cinema.

    PubMed

    García-Sánchez, Jose Elias; García-Sánchez, E; Merino Marcos, M L

    2007-03-01

    Among the antimicrobial agents, antibacterials are the most frequently mentioned in cinematographic plots. Nevertheless, it is not uncommon to come across other antiviral agents, especially antiretrovirals and antiprotozoals. We analyzed the presence of antiviral and antifungal agents in different commercial films, both when they were merely mentioned in passing and when they played a major role in the film. This review essentially aims to address the historical portrayal of these agents in film and to list their appearances. The fictional treatments that appear in some films are not addressed.

  14. Antifungal properties of lectin and new chitinases from potato tubers.

    PubMed

    Gozia, O; Ciopraga, J; Bentia, T; Lungu, M; Zamfirescu, I; Tudor, R; Roseanu, A; Nitu, F

    1993-08-01

    We have purified from potato tubers, the lectin STA devoid of chitinase activity and two chitinases devoid of lectin activity. Both enzymes are 16 kDa glycoproteins, and probably belong to a new family of plant chitinases. The respective antifungal properties of lectin and chitinases were studied by following their effects against early developmental stages of Fusarium oxysporum, a fungal potato pathogen. Here we demonstrate that: (1) lectin does not inhibit mycelial growth but irreversibly inhibits conidia germination and alters the germ tubes; and (2) chitinases block mycelial growth as well as conidia germination and lyse germ tubes.

  15. 3-Methoxysampangine, a novel antifungal copyrine alkaloid from Cleistopholis patens.

    PubMed Central

    Liu, S C; Oguntimein, B; Hufford, C D; Clark, A M

    1990-01-01

    Further examination of the active ethanolic extract of the root bark of Cleistopholis patens by using bioassay-directed fractionation resulted in the isolation of a new alkaloid, 3-methoxysampangine (compound I), together with three known alkaloids, eupolauridine (compound II), liriodenine (compound III), and eupolauridine N-oxide (compound IV). The proposed structure of compound I was based on its physicochemical properties and spectral data. 3-Methoxysampangine exhibited significant antifungal activity against Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. This is the first report of the isolation of liriodenine (compound III) from the root bark of C. patens. PMID:2188584

  16. [Recommendations of antifungal treatment in patients with low grade immunosuppression].

    PubMed

    Barberán, J; Mensa, J; Fariñas, C; Llinares, P; Serrano, R; Menéndez, R; Agustí, C; Gobernado, M; Azanza, J R; García Rodríguez, J A

    2008-06-01

    Because of the relevance that the systemic mycoses has acquired in non-highly immunocompromised patients, the treatment difficulties they have due to the increase of the non-albicans Candida species and the need to have a better and more rational use of the new antifungal agents (voriconazole, posaconazole, caspofungin, anidulafungin and micafungin), an experts' panel on infectious diseases in representation of the Spanish Society of Chemotherapy, Spanish Society of Internal Medicine, and Spanish Society of Pneumology and Thoracic Surgery has met in order to make a few recommendations based on the scientific evidence in an effort to improve their efficiency.

  17. A potential microRNA signature for tumorigenic conazoles in mouse liver.

    PubMed

    Ross, Jeffrey A; Blackman, Carl F; Thai, Sheau-Fung; Li, Zhiguang; Kohan, Michael; Jones, Carlton P; Chen, Tao

    2010-04-01

    Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants of conazole tumorigenicity, we analyzed the microRNA expression levels in control and conazole-treated mice after 90 d of administration in feed. MicroRNAs (miRNAs) are small noncoding RNAs composed of approximately 19-24 nucleotides in length, and have been shown to interact with mRNA (usually 3' UTR) to suppress its expression. MicroRNAs play a key role in diverse biological processes, including development, cell proliferation, differentiation, and apoptosis. Groups of mice were fed either control diet or diet containing 1800 ppm triadimefon, 2500 ppm propiconazole, or 2000 ppm myclobutanil. MicroRNA was isolated from livers and analyzed using Superarray whole mouse genome miRNA PCR arrays from SABioscience. Data were analyzed using the significance analysis of microarrays (SAM) procedure. We identified those miRNAs whose expression was either increased or decreased relative to untreated controls with q < or = 0.01. The tumorigenic conazoles induced many more changes in miRNA expression than the nontumorigenic conazole. A group of 19 miRNAs was identified whose expression was significantly altered in both triadimefon- and propiconazole-treated animals but not in myclobutanil-treated animals. All but one of the altered miRNAs were downregulated compared to controls. This pattern of altered miRNA expression may represent a signature for tumorigenic conazole exposure in mouse liver after 90 d of treatment.

  18. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    SciTech Connect

    Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

    2009-01-15

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  19. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo.

    PubMed

    Chen, Pei-Jen; Padgett, William T; Moore, Tanya; Winnik, Witold; Lambert, Guy R; Thai, Sheau-Fung; Hester, Susan D; Nesnow, Stephen

    2009-01-15

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  20. An overview about the medical use of antifungals in Portugal in the last years.

    PubMed

    Manuel da S Azevedo, Maria; Cruz, Luisa; Pina-Vaz, Cidália; Gonçalves-Rodrigues, Acácio

    2016-05-01

    Despite the introduction of new antifungal agents, the frequency of invasive and mucocutaneous fungal infections as well as resistance to antifungal drugs continues to increase. Over 300 million persons are infected annually with fungi. Resistance to antimicrobials is one of today's major health threats. Can the possible causes of fungal antimicrobial resistance be understood and prevented to minimize risks to public health. We provide an overview of antifungal drug use in European countries, particularly Portugal. We reviewed prescriptions for and over-the-counter sales (OTC) of azoles in Portuguese pharmacies and in alternative shops. We conclude that in Portugal, azole antifungal sales, as well as medical prescribed azoles are very high. The Portuguese population consumes more antifungal drugs per capita than others in Europe. PMID:26865319

  1. Detection and partial characterization of antifungal bioactivity from the secretions of the medicinal maggot, Lucilia sericata.

    PubMed

    Evans, Rhys; Dudley, Ed; Nigam, Yamni

    2015-01-01

    The antibacterial properties of the excretions/secretions (ES) of the medicinal maggot, Lucilia sericata have long been known and the effectiveness of maggot debridement therapy in relation to the clearance of bacteria from the surface of wounds has been the source of much research over recent years. Less well known, however, are the antifungal properties of L. sericata ES. Here, we show by means of the colony forming unit assay and optical density assays, that L. sericata native ES possess significant antifungal properties and appears to possess a highly heat stable, freeze/thaw, and lyophilization resistant antifungal component. We also show that the antifungal activity present in the native ES consists of a number of antifungal components present in three fraction masses consisting of >10, 10-0.5, and <0.5 kDa, with the greatest level of activity being seen in the <0.5 kDa fraction.

  2. Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans

    PubMed Central

    Cui, Jinhui; Ren, Biao; Tong, Yaojun; Dai, Huanqin; Zhang, Lixin

    2015-01-01

    Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi-drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections. PMID:26048362

  3. The effects of Paenibacillus polymyxa E681 on antifungal and crack remediation of cement paste.

    PubMed

    Park, Sung-Jin; Park, Seung-Hwan; Ghim, Sa-Youl

    2014-10-01

    This study investigated the antifungal effects of cement paste containing Paenibacillus polymyxa E681 against Aspergillus niger, a deleterious fungus commonly found in cement buildings and structures. To test the antifungal effects, cement paste containing P. polymyxa E681 was neutralized by CO2 gas, and the fungal growth inhibition was examined according to the clear zone around the cement specimen. In addition to the antifungal effects of the cement paste added with bacteria, calcium crystal precipitation of P. polymyxa E681 was examined by qualitative and quantitative analyses. The cement paste containing P. polymyxa E681 showed strong antifungal effects but fusA mutant (deficient in fusaricidin synthesis) showed no antifungal activity. Crack sealing of the cement paste treated with P. polymyxa E681 was captured by light microscope showed fungal growth inhibition and crack repairing in cement paste.

  4. The effects of Paenibacillus polymyxa E681 on antifungal and crack remediation of cement paste.

    PubMed

    Park, Sung-Jin; Park, Seung-Hwan; Ghim, Sa-Youl

    2014-10-01

    This study investigated the antifungal effects of cement paste containing Paenibacillus polymyxa E681 against Aspergillus niger, a deleterious fungus commonly found in cement buildings and structures. To test the antifungal effects, cement paste containing P. polymyxa E681 was neutralized by CO2 gas, and the fungal growth inhibition was examined according to the clear zone around the cement specimen. In addition to the antifungal effects of the cement paste added with bacteria, calcium crystal precipitation of P. polymyxa E681 was examined by qualitative and quantitative analyses. The cement paste containing P. polymyxa E681 showed strong antifungal effects but fusA mutant (deficient in fusaricidin synthesis) showed no antifungal activity. Crack sealing of the cement paste treated with P. polymyxa E681 was captured by light microscope showed fungal growth inhibition and crack repairing in cement paste. PMID:24824950

  5. Antifungal susceptibilities of non-Aspergillus filamentous fungi causing invasive infection in Australia: support for current antifungal guideline recommendations.

    PubMed

    Halliday, Catriona L; Chen, Sharon C-A; Kidd, Sarah E; van Hal, Sebastian; Chapman, Belinda; Heath, Christopher H; Lee, Andie; Kennedy, Karina J; Daveson, Kathryn; Sorrell, Tania C; Morrissey, C Orla; Marriott, Deborah J; Slavin, Monica A

    2016-10-01

    Antifungal susceptibilities of non-Aspergillus filamentous fungal pathogens cannot always be inferred from their identification. Here we determined, using the Sensititre(®) YeastOne(®) YO10 panel, the in vitro activities of nine antifungal agents against 52 clinical isolates of emergent non-Aspergillus moulds representing 17 fungal groups in Australia. Isolates comprised Mucorales (n = 14), Scedosporium/Lomentospora spp. (n = 18) and a range of hyaline hyphomycetes (n = 9) and other dematiaceous fungi (n = 11). Excluding Verruconis gallopava, echinocandins demonstrated poor activity (MICs generally >8 mg/L) against these moulds. Lomentospora prolificans (n = 4) and Fusarium spp. (n = 6) demonstrated raised MICs to all antifungal drugs tested, with the lowest being to voriconazole and amphotericin B (AmB), respectively (geometric mean MICs of 3.4 mg/L and 2.2 mg/L, respectively). All Scedosporium apiospermum complex isolates (n = 14) were inhibited by voriconazole concentrations of ≤0.25 mg/L, followed by posaconazole and itraconazole at ≤1 mg/L. Posaconazole and AmB were the most active agents against the Mucorales, with MIC90 values of 1 mg/L and 2 mg/L, respectively, for Rhizopus spp. For dematiaceous fungi, all isolates were inhibited by itraconazole and posaconazole concentrations of ≤0.5 mg/L (MIC90, 0.12 mg/L and 0.25 mg/L, respectively), but voriconazole and AmB also had in vitro activity (MIC90, 0.5 mg/L and 1 mg/L, respectively). Differences in antifungal susceptibility within species and between species within genera support the need for testing individual patient isolates to guide therapy. The Sensititre(®) YeastOne(®) offers a practical alternative to the reference methodology for susceptibility testing of moulds.

  6. Structural Basis of Human CYP51 Inhibition by Antifungal Azoles

    SciTech Connect

    Strushkevich, Natallia; Usanov, Sergey A.; Park, Hee-Won

    2010-09-22

    The obligatory step in sterol biosynthesis in eukaryotes is demethylation of sterol precursors at the C14-position, which is catalyzed by CYP51 (sterol 14-alpha demethylase) in three sequential reactions. In mammals, the final product of the pathway is cholesterol, while important intermediates, meiosis-activating sterols, are produced by CYP51. Three crystal structures of human CYP51, ligand-free and complexed with antifungal drugs ketoconazole and econazole, were determined, allowing analysis of the molecular basis for functional conservation within the CYP51 family. Azole binding occurs mostly through hydrophobic interactions with conservative residues of the active site. The substantial conformational changes in the B{prime} helix and F-G loop regions are induced upon ligand binding, consistent with the membrane nature of the protein and its substrate. The access channel is typical for mammalian sterol-metabolizing P450 enzymes, but is different from that observed in Mycobacterium tuberculosis CYP51. Comparison of the azole-bound structures provides insight into the relative binding affinities of human and bacterial P450 enzymes to ketoconazole and fluconazole, which can be useful for the rational design of antifungal compounds and specific modulators of human CYP51.

  7. ANTIFUNGAL POTENTIAL OF PLANT SPECIES FROM BRAZILIAN CAATINGA AGAINST DERMATOPHYTES

    PubMed Central

    BIASI-GARBIN, Renata Perugini; DEMITTO, Fernanda de Oliveira; do AMARAL, Renata Claro Ribeiro; FERREIRA, Magda Rhayanny Assunção; SOARES, Luiz Alberto Lira; SVIDZINSKI, Terezinha Inez Estivalet; BAEZA, Lilian Cristiane; YAMADA-OGATTA, Sueli Fumie

    2016-01-01

    Trichophyton rubrum and Trichophyton mentagrophytes complex, or Trichophyton spp. are the main etiologic agents of dermatophytosis, whose treatment is limited by the high cost of antifungal treatments, their various side effects, and the emergence of resistance amongst these species. This study evaluated the in vitro antidermatophytic activity of 23 crude extracts from nine plant species of semiarid vegetation (caatinga) found in Brazil. The extracts were tested at concentrations ranging from 1.95 to 1,000.0 mg/mL by broth microdilution assay against the reference strains T. rubrum ATCC 28189 and T. mentagrophytesATCC 11481, and 33 clinical isolates of dermatophytes. All plants showed a fungicidal effect against both fungal species, with MIC/MFC values of the active extracts ranging from 15.6 to 250.0 µg/mL. Selected extracts of Eugenia uniflora (AcE), Libidibia ferrea (AE), and Persea americana (AcE) also exhibited a fungicidal effect against all clinical isolates of T. rubrum and T. mentagrophytes complex. This is the first report of the antifungal activity of Schinus terebinthifolius, Piptadenia colubrina, Parapiptadenia rigida, Mimosa ophthalmocentra, and Persea americana against both dermatophyte species. PMID:27007561

  8. Antifungal activity from Ocimum gratissimum L. towards Cryptococcus neoformans.

    PubMed

    Lemos, Janine de Aquino; Passos, Xisto Sena; Fernandes, Orionalda de Fátima Lisboa; Paula, José Realino de; Ferri, Pedro Henrique; Souza, Lúcia Kioko Hasimoto E; Lemos, Aline de Aquino; Silva, Maria do Rosário Rodrigues

    2005-02-01

    Cryptococcal infection had an increased incidence in last years due to the explosion of acquired immune deficiency syndrome epidemic and by using new and effective immunosuppressive agents. The currently antifungal therapies used such as amphotericin B, fluconazole, and itraconazole have certain limitations due to side effects and emergence of resistant strains. So, a permanent search to find new drugs for cryptococcosis treatment is essential. Ocimum gratissimum, plant known as alfavaca (Labiatae family), has been reported earlier with in vitro activity against some bacteria and dermatophytes. In our work, we study the in vitro activity of the ethanolic crude extract, ethyl acetate, hexane, and chloroformic fractions, essential oil, and eugenol of O. gratissimum using an agar dilution susceptibility method towards 25 isolates of Cryptococcus neoformans. All the extracts of O. gratissimum studied showed activity in vitro towards C. neoformans. Based on the minimal inhibitory concentration values the most significant results were obtained with chloroformic fraction and eugenol. It was observed that chloroformic fraction inhibited 23 isolates (92%) of C. neoformans at a concentration of 62.5 microg/ml and eugenol inhibited 4 isolates (16%) at a concentration of 0.9 microg/ml. This screening may be the basis for the study of O. gratissimum as a possible antifungal agent. PMID:15867965

  9. A novel antifungal protein of Bacillus subtilis B25.

    PubMed

    Tan, Zhiqiong; Lin, Baoying; Zhang, Rongyi

    2013-01-01

    Bacillus subtilis B25 was isolated from banana rhizosphere soil. It has been confirmed for B25 to have stronger antagonism against Fusarium oxysporum f.sp.cubense, Additionally B25 has good inhibitory to plant pathogens, including Corynespora cassiicola, Alternaria solani, Botrytis cinerea and Colletotrichum gloeosporioides on potato dextrose agar (PDA) plates. The antagonistic substance can be extracted from cell-free culture broth supernatants by 70% (w/v) (NH4)2 SO4 saturation. Clear blank band was observed between the protein and a pathogen. The examination of antagonistic mechanism under light microscope showed that the antifungal protein of B25 appeared to inhibit pathogens by leading to mycelium and spores tumescence, distortion, abnormality. The isolation procedure comprised ion exchange chromatography on DEAE-Sephadex Fast Flow and gel filtration chromatography on SephadexG-100. The purified antifungal fraction showed a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The active fraction was identified by NanoLC-ESI-MS/MS The amino acid sequences of 17 peptides segments were obtained. The analysis of the protein suggested that it was a hypothetical protein (gi154685475), with a relative molecular mass of 38708.67 Da and isoelectric point (pI) of 5.63. PMID:24255843

  10. ANTIFUNGAL POTENTIAL OF PLANT SPECIES FROM BRAZILIAN CAATINGA AGAINST DERMATOPHYTES.

    PubMed

    Biasi-Garbin, Renata Perugini; Demitto, Fernanda de Oliveira; Amaral, Renata Claro Ribeiro do; Ferreira, Magda Rhayanny Assunção; Soares, Luiz Alberto Lira; Svidzinski, Terezinha Inez Estivalet; Baeza, Lilian Cristiane; Yamada-Ogatta, Sueli Fumie

    2016-01-01

    Trichophyton rubrum and Trichophyton mentagrophytes complex, or Trichophyton spp. are the main etiologic agents of dermatophytosis, whose treatment is limited by the high cost of antifungal treatments, their various side effects, and the emergence of resistance amongst these species. This study evaluated the in vitro antidermatophytic activity of 23 crude extracts from nine plant species of semiarid vegetation (caatinga) found in Brazil. The extracts were tested at concentrations ranging from 1.95 to 1,000.0 mg/mL by broth microdilution assay against the reference strains T. rubrum ATCC 28189 and T. mentagrophytes ATCC 11481, and 33 clinical isolates of dermatophytes. All plants showed a fungicidal effect against both fungal species, with MIC/MFC values of the active extracts ranging from 15.6 to 250.0 µg/mL. Selected extracts of Eugenia uniflora (AcE), Libidibia ferrea (AE), and Persea americana (AcE) also exhibited a fungicidal effect against all clinical isolates of T. rubrum and T. mentagrophytes complex. This is the first report of the antifungal activity of Schinus terebinthifolius, Piptadenia colubrina, Parapiptadenia rigida, Mimosa ophthalmocentra, and Persea americana against both dermatophyte species. PMID:27007561

  11. Antifungal activity of lectins against yeast of vaginal secretion

    PubMed Central

    Gomes, Bruno Severo; Siqueira, Ana Beatriz Sotero; de Cássia Carvalho Maia, Rita; Giampaoli, Viviana; Teixeira, Edson Holanda; Arruda, Francisco Vassiliepe Sousa; do Nascimento, Kyria Santiago; de Lima, Adriana Nunes; Souza-Motta, Cristina Maria; Cavada, Benildo Sousa; Porto, Ana Lúcia Figueiredo

    2012-01-01

    Lectins are carbohydrate-binding proteins of non-imune origin. This group of proteins is distributed widely in nature and they have been found in viruses, microorganisms, plants and animals. Lectins of plants have been isolated and characterized according to their chemical, physical-chemical, structural and biological properties. Among their biological activities, we can stress its fungicidal action. It has been previously described the effect of the lectins Dviol, DRL, ConBr and LSL obtained from the seeds of leguminous plants on the growth of yeasts isolated from vaginal secretions. In the present work the experiments were carried out in microtiter plates and the results interpreted by both methods: visual observations and a microplate reader at 530nm. The lectin concentrations varied from 0.5 to 256μg/mL, and the inoculum was established between 65-70% of trammitance. All yeast samples isolated from vaginal secretion were evaluated taxonomically, where were observed macroscopic and microscopic characteristics to each species. The LSL lectin did not demonstrate any antifungal activity to any isolate studied. The other lectins DRL, ConBr and DvioL, showed antifungal potential against yeast isolated from vaginal secretion. These findings offering offer a promising field of investigation to develop new therapeutic strategies against vaginal yeast infections, collaborating to improve women's health. PMID:24031889

  12. Novel, Synergistic Antifungal Combinations that Target Translation Fidelity.

    PubMed

    Moreno-Martinez, Elena; Vallieres, Cindy; Holland, Sara L; Avery, Simon V

    2015-11-17

    There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ≥8-fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone.

  13. Antifungal and antioxidant activities of the phytomedicine pipsissewa, Chimaphila umbellata.

    PubMed

    Galván, Imelda J; Mir-Rashed, Nadereh; Jessulat, Matthew; Atanya, Monica; Golshani, Ashkan; Durst, Tony; Petit, Philippe; Amiguet, Virginie Treyvaud; Boekhout, Teun; Summerbell, Richard; Cruz, Isabel; Arnason, John T; Smith, Myron L

    2008-02-01

    Bioassay-guided fractionation of Chimaphila umbellata (L.) W. Bart (Pyrolaceae) ethanol extracts led to the identification of 2,7-dimethyl-1,4-naphthoquinone (chimaphilin) as the principal antifungal component. The structure of chimaphilin was confirmed by 1H and 13C NMR spectroscopy. The antifungal activity of chimaphilin was evaluated using the microdilution method with Saccharomyces cerevisiae (0.05mg/mL) and the dandruff-associated fungi Malassezia globosa (0.39mg/mL) and Malassezia restricta (0.55mg/mL). Pronounced antioxidant activity of C. umbellata crude extract was also identified using the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, suggesting this phytomedicine has an antioxidant function in wound healing. A chemical-genetic profile was completed with chimaphilin using approximately 4700 S. cerevisiae gene deletion mutants. Cellular roles of deleted genes in the most susceptible mutants and secondary assays indicate that the targets for chimaphilin include pathways involved in cell wall biogenesis and transcription. PMID:17950387

  14. Onychomycosis: Potential of Nail Lacquers in Transungual Delivery of Antifungals

    PubMed Central

    Sharma, Hemlata; Pathak, Kamla

    2016-01-01

    Onychomycosis constitutes the most common fungal infection of the nail (skin beneath the nail bed) that affects the finger as well as toe nails. It is an infection that is initiated by yeasts, dermatophytes, and nondermatophyte molds. Nail lacquers are topical solutions intended only for use on fingernails as well as toenails and have been found to be useful in the treatment of onychomycosis. Thus, in the present review an attempt has been made to focus on the treatment aspects of onychomycosis and the ungual delivery of antifungals via nail lacquer. Several patents issued on nail lacquer till date have also been discussed. Penetration efficiency was assessed by several researchers across the human nail plate to investigate the potentiality of nail lacquer based formulations. Various clinical trials have also been conducted in order to evaluate the safety and efficacy of nail lacquers in delivering antifungal agents. Thus, it can be concluded that nail lacquer based preparations are efficacious and stable formulations. These possess tremendous potential for clinical topical application to the nail bed in the treatment of onychomycosis. PMID:27123362

  15. Benzoic acid derivatives with improved antifungal activity: Design, synthesis, structure-activity relationship (SAR) and CYP53 docking studies.

    PubMed

    Berne, Sabina; Kovačič, Lidija; Sova, Matej; Kraševec, Nada; Gobec, Stanislav; Križaj, Igor; Komel, Radovan

    2015-08-01

    Previously, we identified CYP53 as a fungal-specific target of natural phenolic antifungal compounds and discovered several inhibitors with antifungal properties. In this study, we performed similarity-based virtual screening and synthesis to obtain benzoic acid-derived compounds and assessed their antifungal activity against Cochliobolus lunatus, Aspergillus niger and Pleurotus ostreatus. In addition, we generated structural models of CYP53 enzyme and used them in docking trials with 40 selected compounds. Finally, we explored CYP53-ligand interactions and identified structural elements conferring increased antifungal activity to facilitate the development of potential new antifungal agents that specifically target CYP53 enzymes of animal and plant pathogenic fungi. PMID:26154240

  16. Synthesis, Characterization and Antifungal Evaluation of Novel Thiochromanone Derivatives Containing Indole Skeleton.

    PubMed

    Han, Xiao-Yan; Zhong, Yi-Fan; Li, Sheng-Bin; Liang, Guo-Chao; Zhou, Guan; Wang, Xiao-Ke; Chen, Bao-Hua; Song, Ya-Li

    2016-09-01

    Invasive fungal disease constitutes a growing health problem and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. In order to develop potent antifungal agents, a novel series of 6-alkyl-indolo[3,2-c]-2H-thiochroman derivatives were synthesized. Microdilution broth method was used to investigate antifungal activity of these compounds. Most of them showed good antifungal activity in vitro. Compound 4o showed the best antifungal activity, which (inhibition of Candida albicans and Cryptococcus neoformans) can be achieved at the concentration of 4 µg/mL. Compounds 4b (inhibition of Cryptococcus neoformans), 4j (inhibition of Cryptococcus neoformans), 4d (inhibition of Candida albicans) and 4h (inhibition of Candida albicans) also showed the best antifungal activity at the concentrations of 4 µg/mL. The molecular interactions between 4o and the N-myristoyltransferase of Candida albicans (PDB ID: 1IYL) were finally investigated through molecular docking. The results indicated that these thiochromanone derivatives containing indole skeleton could serve as promising leads for further optimization as novel antifungal agents. PMID:27373770

  17. Antifungal Activity of Bee Venom and Sweet Bee Venom against Clinically Isolated Candida albicans

    PubMed Central

    Lee, Seung-Bae

    2016-01-01

    Objectives: The purpose of this study was to investigate the antifungal effect of bee venom (BV) and sweet bee venom (SBV) against Candida albicans (C. albicans) clinical isolates. Methods: In this study, BV and SBV were examined for antifungal activities against the Korean Collection for Type Cultures (KCTC) strain and 10 clinical isolates of C. albicans. The disk diffusion method was used to measure the antifungal activity and minimum inhibitory concentration (MIC) assays were performed by using a broth microdilution method. Also, a killing curve assay was conducted to investigate the kinetics of the anti- fungal action. Results: BV and SBV showed antifungal activity against 10 clinical isolates of C. albicans that were cultured from blood and the vagina by using disk diffusion method. The MIC values obtained for clinical isolates by using the broth microdilution method varied from 62.5 μg/ mL to 125 μg/mL for BV and from 15.63 μg/mL to 62.5 μg/mL for SBV. In the killing-curve assay, SBV behaved as amphotericin B, which was used as positive control, did. The antifungal efficacy of SBV was much higher than that of BV. Conclusion: BV and SBV showed antifungal activity against C. albicans clinical strains that were isolated from blood and the vagina. Especially, SBV might be a candidate for a new antifungal agent against C. albicans clinical isolates. PMID:27280049

  18. The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals against Candida parapsilosis species complex.

    PubMed

    Cordeiro, Rossana de Aguiar; Macedo, Ramila de Brito; Teixeira, Carlos Eduardo Cordeiro; Marques, Francisca Jakelyne de Farias; Bandeira, Tereza de Jesus Pinheiro Gomes; Moreira, José Luciano Bezerra; Brilhante, Raimunda Sâmia Nogueira; Rocha, Marcos Fábio Gadelha; Sidrim, José Júlio Costa

    2014-07-01

    Candida parapsilosis complex comprises three closely related species, C. parapsilosis sensu stricto, Candida metapsilosis and Candida orthopsilosis. In the last decade, antifungal resistance to azoles and caspofungin among C. parapsilosis sensu lato strains has been considered a matter of concern worldwide. In the present study, we evaluated the synergistic potential of antifungals and the calcineurin inhibitor cyclosporin A (Cys) against planktonic and biofilms of C. parapsilosis complex from clinical sources. Susceptibility assays with amphotericin, fluconazole, voriconazole, caspofungin and Cys were performed by microdilution in accordance with Clinical and Laboratory Standards Institute guidelines. Synergy testing against planktonic cells of C. parapsilosis sensu lato strains was assessed by the chequerboard method. Combinations formed by antifungals with Cys were evaluated against mature biofilms in microtitre plates. No differences in the antifungal susceptibility pattern among species were observed, but C. parapsilosis sensu stricto strains were more susceptible to Cys than C. orthopsilosis and C. metapsilosis. Synergism between antifungals and Cys was observed in C. parapsilosis sensu lato strains. Combinations formed by antifungals and Cys were able to prevent biofilm formation and showed an inhibitory effect against mature biofilms of C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis. These results strengthen the potential of calcineurin inhibition as a promising approach to enhance the efficiency of antifungal drugs. PMID:24722799

  19. Contribution of volatiles to the antifungal effect of Lactobacillus paracasei in defined medium and yogurt.

    PubMed

    Aunsbjerg, S D; Honoré, A H; Marcussen, J; Ebrahimi, P; Vogensen, F K; Benfeldt, C; Skov, T; Knøchel, S

    2015-02-01

    Lactic acid bacteria with antifungal properties can be used to control spoilage of food and feed. Previously, most of the identified metabolites have been isolated from cell-free fermentate of lactic acid bacteria with methods suboptimal for detecting possible contribution from volatiles to the antifungal activity. The role of volatile compounds in the antifungal activity of Lactobacillus paracasei DGCC 2132 in a chemically defined interaction medium (CDIM) and yogurt was therefore investigated with a sampling technique minimizing volatile loss. Diacetyl was identified as the major volatile produced by L. paracasei DGCC 2132 in CDIM. When the strain was added to a yogurt medium diacetyl as well as other volatiles also increased but the metabolome was more complex. Removal of L. paracasei DGCC 2132 cells from CDIM fermentate resulted in loss of both volatiles, including diacetyl, and the antifungal activity towards two strains of Penicillium spp. When adding diacetyl to CDIM or yogurt without L. paracasei DGCC 2132, marked inhibition was observed. Besides diacetyl, the antifungal properties of acetoin were examined, but no antifungal activity was observed. Overall, the results demonstrate the contribution of diacetyl in the antifungal effect of L. paracasei DGCC 2132 and indicate that the importance of volatiles may have been previously underestimated.

  20. In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections

    PubMed Central

    Yuen, Kwok Yong; Wang, Yu; Yang, Dan; Samaranayake, Lakshman Perera

    2014-01-01

    Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use. PMID:24465737

  1. In vitro and in vivo activity of a novel antifungal small molecule against Candida infections.

    PubMed

    Wong, Sarah Sze Wah; Kao, Richard Yi Tsun; Yuen, Kwok Yong; Wang, Yu; Yang, Dan; Samaranayake, Lakshman Perera; Seneviratne, Chaminda Jayampath

    2014-01-01

    Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2-1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use. PMID:24465737

  2. Porosity of temporary denture soft liners containing antifungal agents

    PubMed Central

    Lima, Jozely Francisca Mello; Maciel, Janaína Gomes; Hotta, Juliana; Vizoto, Ana Carolina Pero; Honório, Heitor Marques; Urban, Vanessa Migliorini; Neppelenbroek, Karin Hermana

    2016-01-01

    ABSTRACT Incorporation of antifungals in temporary denture soft liners has been recommended for denture stomatitis treatment; however, it may affect their properties. Objective: To evaluate the porosity of a tissue conditioner (Softone) and a temporary resilient liner (Trusoft) modified by minimum inhibitory concentrations (MICs) of antifungal agents for Candida albicans biofilm. Material and Methods: The porosity was measured by water absorption, based on exclusion of the plasticizer effect. Initially, it was determined by sorption isotherms that the adequate storage solution for specimens (65×10×3.3 mm) of both materials was 50% anhydrous calcium chloride (S50). Then, the porosity factor (PF) was calculated for the study groups (n=10) formed by specimens without (control) or with drug incorporation at MICs (nystatin: Ny-0.032 g, chlorhexidine diacetate: Chx-0.064 g, or ketoconazole: Ke-0.128 g each per gram of soft liner powder) after storage in distilled water or S50 for 24 h, seven and 14 d. Data were statistically analyzed by 4-way repeated measures ANOVA and Tukey's test (α=.05). Results: Ke resulted in no significant changes in PF for both liners in water over 14 days (p>0.05). Compared with the controls, Softone and Trusoft PFs were increased at 14-day water immersion only after addition of Ny and Chx, and Chx, respectively (p<0.05). Both materials showed no significant changes in PF in up to 14 days of S50 immersion, compared with the controls (p>0.05). In all experimental conditions, Softone and Trusoft PFs were significantly lower when immersed in S50 compared with distilled water (p<0.05). Conclusions: The addition of antifungals at MICs resulted in no harmful effects for the porosity of both temporary soft liners in different periods of water immersion, except for Chx and Ny in Softone and Chx in Trusoft at 14 days. No deleterious effect was observed for the porosity of both soft liners modified by the drugs at MICs over 14 days of S50 immersion

  3. Clauraila E from the roots of Clausena harmandiana and antifungal activity against Pythium insidiosum.

    PubMed

    Sriphana, Uraiwan; Thongsri, Yordhathai; Prariyachatigul, Chularut; Pakawatchai, Chaveng; Yenjai, Chavi

    2013-09-01

    A new carbazole alkaloid named clauraila E (1) together with 8 known compounds were isolated from the methanol extract of the roots of Clausena harmandiana. All compounds were evaluated for antifungal activity against Pythium insidiosum using disc diffusion assay. Pythium insidiosum is a fungus-like microorganism, for which antifungals available now are not effective. It was found that compounds 3, 6, 7 and 9 could inhibit the mycelia growth of P. insidiosum. The results show convincingly that they may be lead to compounds for the development of probiotic or novel antifungal drugs. PMID:23595552

  4. Combinatorial synthesis of benzimidazole-azo-phenol derivatives as antifungal agents.

    PubMed

    Ke, Yazhen; Zhi, Xiaoyan; Yu, Xiang; Ding, Guodong; Yang, Chun; Xu, Hui

    2014-01-01

    A chemically diverse library of benzimidazole-azo-phenol derivatives was efficiently prepared and screened for their antifungal activities against five phytopathogenic fungi. Some compounds exhibited potent antifungal activities. As compared with a commercially available agricultural fungicide, hymexazol, especially compound V-5 showed the most promising broad-spectrum antifungal activities against five phytopathogenic fungi. The EC50 values of V-5 against F. graminearum, A. solani, V. mali, B. cinerea, and C. lunata were 0.09, 0.08, 0.06, 0.07, and 0.11 μmol/mL, respectively. PMID:24152176

  5. Enhancement of the Antifungal Activity of Antimicrobial Drugs by Eugenia uniflora L.

    PubMed Central

    Santos, Karla K.A.; Matias, Edinardo F.F.; Tintino, Saulo R.; Souza, Celestina E.S.; Braga, Maria F.B.M.; Guedes, Gláucia M.M.; Costa, José G.M.; Menezes, Irwin R.A.

    2013-01-01

    Abstract Candidiasis is the most frequent infection by opportunistic fungi such as Candida albicans, Candida tropicalis, and Candida krusei. Ethanol extract from Eugenia uniflora was assayed, for its antifungal activity, either alone or combined with four selected chemotherapeutic antimicrobial agents, including anphotericin B, mebendazole, nistatin, and metronidazole against these strains. The obtained results indicated that the association of the extract of E. uniflora to metronidazole showed a potential antifungal activity against C. tropicalis. However, no synergistic activity against the other strains was observed, as observed when the extract was associated with the other, not enhancing their antifungal activity. PMID:23819641

  6. Bioassay-guided isolation and identification of antifungal compounds from ginger.

    PubMed

    Ficker, C; Smith, M L; Akpagana, K; Gbeassor, M; Zhang, J; Durst, T; Assabgui, R; Arnason, J T

    2003-09-01

    A bioassay-guided isolation of antifungal compounds from an African land race of ginger, Zingiber officinale Roscoe, led to the identification of [6], [8] and [10]-gingerols and [6]-gingerdiol as the main antifungal principles. The compounds were active against 13 human pathogens at concentrations of <1 mg/mL. The gingerol content of the African land race was at least 3 x higher than that of typical commercial cultivars of ginger. Therefore, ginger extracts standardized on the basis of the identified compounds, could be considered as antifungal agents for practical therapy. PMID:13680820

  7. Update from the Laboratory: Clinical Identification and Susceptibility Testing of Fungi and Trends in Antifungal Resistance.

    PubMed

    Albataineh, Mohammad T; Sutton, Deanna A; Fothergill, Annette W; Wiederhold, Nathan P

    2016-03-01

    Despite the availability of new diagnostic assays and broad-spectrum antifungal agents, invasive fungal infections remain a significant challenge to clinicians and are associated with marked morbidity and mortality. In addition, the number of etiologic agents of invasive mycoses has increased accompanied by an expansion in the immunocompromised patient populations, and the use of molecular tools for fungal identification and characterization has resulted in the discovery of several cryptic species. This article reviews various methods used to identify fungi and perform antifungal susceptibility testing in the clinical laboratory. Recent developments in antifungal resistance are also discussed. PMID:26739605

  8. In Vitro Activities of 10 Antifungal Drugs against 508 Dermatophyte Strains

    PubMed Central

    Fernández-Torres, B.; Carrillo, A. J.; Martín, E.; Del Palacio, A.; Moore, M. K.; Valverde, A.; Serrano, M.; Guarro, J.

    2001-01-01

    We have tested 508 strains belonging to 24 species of dermatophytes against 10 antifungal drugs following mainly the NCCLS (M38-P) standard for filamentous fungi. However, several important factors, such as the temperature (28 versus 35°C) and time of incubation (4 to 10 days versus 21 to 74 h), have been modified. The antifungals used were itraconazole, ketoconazole, miconazole, clotrimazole, voriconazole, terbinafine, amphotericin B, fluconazole, UR-9825, and G-1. In general, with the exception of fluconazole and G-1, all antifungals were shown to be highly effective. PMID:11502524

  9. Potential Targets for Antifungal Drug Discovery Based on Growth and Virulence in Candida albicans

    PubMed Central

    Li, Xiuyun; Hou, Yinglong; Yue, Longtao; Liu, Shuyuan; Du, Juan

    2015-01-01

    Fungal infections, especially infections caused by Candida albicans, remain a challenging problem in clinical settings. Despite the development of more-effective antifungal drugs, their application is limited for various reasons. Thus, alternative treatments with drugs aimed at novel targets in C. albicans are needed. Knowledge of growth and virulence in fungal cells is essential not only to understand their pathogenic mechanisms but also to identify potential antifungal targets. This article reviews the current knowledge of the mechanisms of growth and virulence in C. albicans and examines potential targets for the development of new antifungal drugs. PMID:26195510

  10. Characterization of Chitosan Nanofiber Sheets for Antifungal Application

    PubMed Central

    Egusa, Mayumi; Iwamoto, Ryo; Izawa, Hironori; Morimoto, Minoru; Saimoto, Hiroyuki; Kaminaka, Hironori; Ifuku, Shinsuke

    2015-01-01

    Chitosan produced by the deacetylation of chitin is a cationic polymer with antimicrobial properties. In this study, we demonstrate the improvement of chitosan properties by nanofibrillation. Nanofiber sheets were prepared from nanofibrillated chitosan under neutral conditions. The Young’s modulus and tensile strength of the chitosan NF sheets were higher than those of the chitosan sheets prepared from dissolving chitosan in acetic acid. The chitosan NF sheets showed strong mycelial growth inhibition against dermatophytes Microsporum and Trichophyton. Moreover, the chitosan NF sheets exhibited resistance to degradation by the fungi, suggesting potentials long-lasting usage. In addition, surface-deacetylated chitin nanofiber (SDCNF) sheets were prepared. The SDCNF sheet had a high Young’s modulus and tensile strength and showed antifungal activity to dermatophytes. These data indicate that nanofibrillation improved the properties of chitosan. Thus, chitosan NF and SDCNF sheets are useful candidates for antimicrobial materials. PMID:26540046

  11. [Pharmacology of the antifungals used in the treatment of aspergillosis].

    PubMed

    Azanza, José Ramón; Sádaba, Belén; Gómez-Guíu, Almudena

    2014-01-01

    The treatment of invasive aspergillosis requires the use of drugs that characteristically have complex pharmacokinetic properties, the knowledge of which is essential to achieve maximum efficacy with minimal risk to the patient. The lipid-based amphotericin B formulations vary significantly in their pharmacokinetic behaviour, with very high plasma concentrations of the liposomal form, probably related to the presence of cholesterol in their structure. Azoles have a variable absorption profile, particularly in the case of itraconazole and posaconazole, with the latter very dependent on multiple factors. This may also lead to variations in voriconazole, which requires considering the possibility of monitoring plasma concentrations. The aim of this article is to review some of the most relevant aspects of the pharmacology of the antifungals used in the prophylaxis and treatment of the Aspergillus infection. For this reason, it includes the most relevant features of some of the azoles normally prescribed in this infection (itraconazole, posaconazole and voriconazole) and the amphotericin B formulations.

  12. [Innovative antifungals for treatment of invasive fungal infections].

    PubMed

    Glöckner, A

    2011-09-01

    Invasive fungal infections have gained importance in many areas of clinical medicine and represent a growing diagnostic and therapeutic challenge for clinicians. During the last decade, several new antifungals were introduced into routine therapy: two second-generation triazoles and the new class of echinocandins. These innovative drugs showed convincing efficacy and favorable safety in randomized clinical trials. Consequently, they were integrated in recent therapeutic guidelines, often replacing former standard drugs as first-line options. The echinocandins (anidulafungin, caspofungin, micafungin) primarily have gained a central role in the treatment of invasive Candida infections, while the novel triazoles voriconazole and posaconazole established themselves as the current mainstays in therapy and prophylaxis of invasive fungal infections, particularly aspergillosis, in hemato-oncologic high-risk patients.

  13. Antifungal activity of silver nanoparticles obtained by green synthesis.

    PubMed

    Mallmann, Eduardo José J; Cunha, Francisco Afrânio; Castro, Bruno N M F; Maciel, Auberson Martins; Menezes, Everardo Albuquerque; Fechine, Pierre Basílio Almeida

    2015-01-01

    Silver nanoparticles (AgNPs) are metal structures at the nanoscale. AgNPs have exhibited antimicrobial activities against fungi and bacteria; however synthesis of AgNPs can generate toxic waste during the reaction process. Accordingly, new routes using non-toxic compounds have been researched. The proposal of the present study was to synthesize AgNPs using ribose as a reducing agent and sodium dodecyl sulfate (SDS) as a stabilizer. The antifungal activity of these particles against C. albicans and C. tropicalis was also evaluated. Stable nanoparticles 12.5 ± 4.9 nm (mean ± SD) in size were obtained, which showed high activity against Candida spp. and could represent an alternative for fungal infection treatment. PMID:25923897

  14. Partial identification of antifungal compounds from Punica granatum peel extracts.

    PubMed

    Glazer, Ira; Masaphy, Segula; Marciano, Prosper; Bar-Ilan, Igal; Holland, Doron; Kerem, Zohar; Amir, Rachel

    2012-05-16

    Aqueous extracts of pomegranate peels were assayed in vitro for their antifungal activity against six rot fungi that cause fruit and vegetable decay during storage. The growth rates of Alternaria alternata , Stemphylium botryosum , and Fusarium spp. were significantly inhibited by the extracts. The growth rates were negatively correlated with the levels of total polyphenolic compounds in the extract and particularly with punicalagins, the major ellagitannins in pomegranate peels. Ellagitannins were also found to be the main compounds in the bioactive fractions using bioautograms, and punicalagins were identified as the main bioactive compounds using chromatographic separation. These results suggest that ellagitannins, and more specifically punicalagins, which are the dominant compounds in pomegranate peels, may be used as a control agent of storage diseases and to reduce the use of synthetic fungicides. PMID:22533815

  15. Cytotoxic and Antifungal Activities of Diverse α-Naphthylamine Derivatives

    PubMed Central

    Kouznetsov, Vladímir V.; Zacchino, Susana A.; Sortino, Maximiliano; Vargas Méndez, Leonor Y.; Gupta, Mahabir P.

    2012-01-01

    Diverse α-naphthylamine derivatives were easily prepared from corresponding aldimines derived from commercially available α-naphthaldehyde and anilines or isomeric pyridinecarboxyaldehydes and α-naphthylamine. The secondary amines obtained were tested as possible antifungal and cytotoxic agents. The diverse N-aryl-N-[1-(1-naphthyl)but-3-enyl]amines obtained were active (IC50 < 10 μg/mL) against breast (MCF-7), non-small cell lung (H-460), and central nervous system (SF-268) human cancer cell lines, while N-(pyridinylmethyl)-naphthalen-1-amines resulted in activity against (MIC 25–32 μg/mL) some human opportunistic pathogenic fungi including yeasts, hialohyphomycetes, and dermatophytes. PMID:23264936

  16. ANTIFUNGAL ACTIVITY OF SILVER NANOPARTICLES OBTAINED BY GREEN SYNTHESIS

    PubMed Central

    MALLMANN, Eduardo José J.; CUNHA, Francisco Afrânio; CASTRO, Bruno N.M.F.; MACIEL, Auberson Martins; MENEZES, Everardo Albuquerque; FECHINE, Pierre Basílio Almeida

    2015-01-01

    Silver nanoparticles (AgNPs) are metal structures at the nanoscale. AgNPs have exhibited antimicrobial activities against fungi and bacteria; however synthesis of AgNPs can generate toxic waste during the reaction process. Accordingly, new routes using non-toxic compounds have been researched. The proposal of the present study was to synthesize AgNPs using ribose as a reducing agent and sodium dodecyl sulfate (SDS) as a stabilizer. The antifungal activity of these particles against C. albicans and C. tropicalis was also evaluated. Stable nanoparticles 12.5 ± 4.9 nm (mean ± SD) in size were obtained, which showed high activity against Candida spp. and could represent an alternative for fungal infection treatment. PMID:25923897

  17. Characterization of Chitosan Nanofiber Sheets for Antifungal Application.

    PubMed

    Egusa, Mayumi; Iwamoto, Ryo; Izawa, Hironori; Morimoto, Minoru; Saimoto, Hiroyuki; Kaminaka, Hironori; Ifuku, Shinsuke

    2015-11-02

    Chitosan produced by the deacetylation of chitin is a cationic polymer with antimicrobial properties. In this study, we demonstrate the improvement of chitosan properties by nanofibrillation. Nanofiber sheets were prepared from nanofibrillated chitosan under neutral conditions. The Young's modulus and tensile strength of the chitosan NF sheets were higher than those of the chitosan sheets prepared from dissolving chitosan in acetic acid. The chitosan NF sheets showed strong mycelial growth inhibition against dermatophytes Microsporum and Trichophyton. Moreover, the chitosan NF sheets exhibited resistance to degradation by the fungi, suggesting potentials long-lasting usage. In addition, surface-deacetylated chitin nanofiber (SDCNF) sheets were prepared. The SDCNF sheet had a high Young's modulus and tensile strength and showed antifungal activity to dermatophytes. These data indicate that nanofibrillation improved the properties of chitosan. Thus, chitosan NF and SDCNF sheets are useful candidates for antimicrobial materials.

  18. Antifungal constituents from the Chinese moss Homalia trichomanoides.

    PubMed

    Wang, Xiao-ning; Yu, Wen-tao; Lou, Hong-xiang

    2005-01-01

    Bioautographic assay on TLC plates was adopted to guide the fractionation of the Et2O extract of Homalia trichomanoides (Hedw.) B. S. G., which led to the isolation of the novel p-terphenyl derivative trichomanin (= 4,4''-dihydroxy-1,1':4',1''-terphenyl-2',3',5',6'-tetrayl tetrakis(phenylacetate); 1), together with five known compounds: 3alpha-methoxyserrat-14-en-21beta-ol (2), 3beta-methoxyserrat-14-en-21beta-ol (3), 3beta-methoxyserrat-14-en-21-one (4), atranorin (5), and methyl 2,4-dihydroxy-3,6-dimethylbenzoate (6). Their structures were determined on the basis of spectral data (1D- and 2D-NMR, MS), X-ray crystallographic analysis, and chemical transformation. Compounds 3, 5, and 6 exhibited antifungal activity against Candida albicans, with minimum inhibitory doses (MID) of 2.0, 2.0, and 0.6 microg, respectively. PMID:17191927

  19. [MIKAMINOM ANTIFUNGAL THERAPY IN NEWBORNS AND INFANTS WITH SURGICAL PATHOLOGY].

    PubMed

    Melnikova, N I; Strogonov, I A; Kartseva, E V; Haritonova, G D; Gliznutsin, O E; Gabulaev, S V; Pulikova, E M

    2016-01-01

    Prolonged empiric and etiotropic therapy of multidrug-resistant or pan-resistant bacterial flora in different gestation age newborns has led to the growth of resistant fungalflora in intencive care units (ICU). According to risk factors and rating scales every child of ICU undergoing the abdominal cavity surgery is threatened the development of a fungal infection and requires antifungal therapy appointment or causal prophylactic. In recent years, before the advent of medications of the group of echinocandins, therapy of invasive fungal infections has been a challenge. Currently alternative drug to diflucane in neonates and infants is micafungine (mycamine) in the dose of 2-8 mg/kg/day, depending on the signs of infestation and severity of the condition. PMID:27192854

  20. Acetoxychavicol Acetate, an Antifungal Component of Alpinia galanga1.

    PubMed

    Janssen, A M; Scheffer, J J

    1985-12-01

    The essential oils from fresh and dried rhizomes of ALPINIA GALANGA showed an antimicrobial activity against gram-positive bacteria, a yeast and some dermatophytes, using the agar overlay technique. The main components of the oils were also tested and terpinen-4-ol was found most active. An N-pentane/diethyl ether extract of dried rhizomes was active against TRICHOPHYTON MENTAGROPHYTES. 1'-Acetoxychavicol acetate, 1'-acetoxyeugenol acetate and 1'-hydroxychavicol acetate identified by MS and NMR were found in the antifungally active fractions obtained by LSC. Acetoxychavicol acetate was active against the seven fungi tested and its MIC value for dermatophytes ranged from 50 to 250 microg/ml. Dried sliced rhizomes contained 1.5% of this compound. The compound was not found in rhizomes of ALPINIA OFFICINARUM, ZINGIBER OFFICINALE and KAEMPFERIA GALANGA.

  1. Synthesis and antifungal activity of bile acid-derived oxazoles.

    PubMed

    Fernández, Lucía R; Svetaz, Laura; Butassi, Estefanía; Zacchino, Susana A; Palermo, Jorge A; Sánchez, Marianela

    2016-04-01

    Peracetylated bile acids (1a-g) were used as starting materials for the preparation of fourteen new derivatives bearing an oxazole moiety in their side chain (6a-g, 8a-g). The key step for the synthetic path was a Dakin-West reaction followed by a Robinson-Gabriel cyclodehydration. A simpler model oxazole (12) was also synthesized. The antifungal activity of the new compounds (6a-g) as well as their starting bile acids (1a-g) was tested against Candida albicans. Compounds 6e and 6g showed the highest percentages of inhibition (63.84% and 61.40% at 250 μg/mL respectively). Deacetylation of compounds 6a-g, led to compounds 8a-g which showed lower activities than the acetylated derivatives. PMID:26827629

  2. Antifungal and cytotoxic activity of withanolides from Acnistus arborescens.

    PubMed

    Roumy, Vincent; Biabiany, Murielle; Hennebelle, Thierry; Aliouat, El Moukhtar; Pottier, Muriel; Joseph, Henry; Joha, Sami; Quesnel, Bruno; Alkhatib, Racha; Sahpaz, Sevser; Bailleul, François

    2010-07-23

    Three compounds were isolated from Acnistus arborescens, a tree commonly used in South and Central America in traditional medicine against several infectious diseases, some of which are caused by fungi. Bioassay-guided fractionation of a MeOH extract of leaves, based on its anti-Pneumocystis carinii activity, led to the isolation of compounds 1-3. Mono- and bidimensional NMR analyses enabled identification of two new withanolides, (20R,22R)-5beta,6beta-epoxy-4beta,12beta,20-trihydroxy-1-oxowith-2-en-24-enolide (1) and (20R,22R)-16beta-acetoxy-3beta,4beta;5beta,6beta-diepoxy-12beta,20-dihydroxy-1-oxowith-24-enolide (2), and withanolide D (3). Antifungal activity on 13 fungi responsible for human infections (five dermatophytes, one nondermatophyte mold, six yeasts, and Pneumocystis carinii) was examined. Cytotoxicity of these compounds was also evaluated in vitro. PMID:20590148

  3. Antifungal activity of Curcuma longa grown in Thailand.

    PubMed

    Wuthi-udomlert, M; Grisanapan, W; Luanratana, O; Caichompoo, W

    2000-01-01

    Curcuma longa Linn. or turmeric (Zingiberaceae) is a medicinal plant widely used and cultivated in tropical regions. According to Thai traditional texts, fresh and dried rhizomes are used as peptic ulcer treatment, carminatives, wound treatment and anti-inflammatory agent. Using hydro distillation, 1.88% and 7.02% (v/w) volatile oils were extracted from fresh and dried rhizomes, respectively, and 6.95% (w/w)crude curcuminoids were extracted from dried rhizomes. Dried powder was extracted with 95% ethanol and yielded 29.52% (w/w) crude ethanol extract composed of curcumin (11.6%), demethoxycurcumin (10.32%) and bisdemethoxycurcumin (10.77%). These extracts were tested for antifungal activity by agar disc diffusion method against 29 clinical strains of dermatophytes. It was found that crude ethanol extract exhibited an inhibition zone range of 6.1 to 26.0 mm. There was no inhibition activity from crude curcuminoids while curcumin, demethoxycurcumin and bisdemethoxycutcumin gave different inhibition zone diameters ranging from 6.1 to 16.0 mm. Although antifungal activity of undiluted freshly distilled oil and 18-month-old oil revealed some differences, the inhibition zone diameters for both extracts varied within 26.1 to 46.0 mm. With 200 mg/ml ketoconazole, the activities of the standard agent were similar to the oil, both freshly distilled and 18-month-old, but were significantly different from those of curcuminoid compounds and crude ethanol extracts (p < 0.01). Turmeric oil was also tested for its minimum inhibitory concentration (MIC) by broth dilution method. The MICs of freshly distilled and 18-month-old oils were 7.8 and 7.2 mg/ml respectively. PMID:11414453

  4. Antifungal Effect of Plant Essential Oils on Controlling Phytophthora Species.

    PubMed

    Amini, Jahanshir; Farhang, Vahid; Javadi, Taimoor; Nazemi, Javad

    2016-02-01

    In this study, antifungal activity of essential oils of Cymbopogon citratus and Ocimum basilicum and two fungicides Mancozeb and Metalaxyl-Mancozeb in six different concentrations were investigated for controlling three species of Phytophthora, including P. capsici, P. drechsleri and P. melonis on pepper, cucumber and melon under in vitro and greenhouse conditions, respectively. Under the in vitro condition, the median effective concen- tration (EC50) values (ppm) of plant essential oils and fungicides were measured. In greenhouse, soil infested with Phytophthora species was treated by adding 50 ml of essential oils and fungicides (100 ppm). Disease severity was determined after 28 days. Among two tested plant essential oils, C. citratus had the lowest EC50 values for inhibition of the mycelial growth of P. capsici (31.473), P. melonis (33.097) and P. drechsleri (69.112), respectively. The mean EC50 values for Metalaxyl-Mancozeb on these pathogens were 20.87, 20.06 and 17.70, respectively. Chemical analysis of plant essential oils by GC-MS showed that, among 42 compounds identified from C. citratus, two compounds β-geranial (α-citral) (39.16%) and z-citral (30.95%) were the most abundant. Under the greenhouse condition, Metalaxyl-Mancozeb caused the greatest reduction in disease severity, 84.2%, 86.8% and 92.1% on melon, cucumber, and pepper, respectively. The C. citratus essential oil reduced disease severity from 47.4% to 60.5% compared to the untreated control (p≤0.05). Essential oils of O. basilicum had the lowest effects on the pathogens under in vitro and greenhouse conditions. These results show that essential oils may contribute to the development of new antifungal agents to protect the crops from Phytophthora diseases. PMID:26889111

  5. Distribution and antifungal susceptibility of Candida species causing nosocomial candiduria.

    PubMed

    Ozhak-Baysan, Betil; Ogunc, Dilara; Colak, Dilek; Ongut, Gozde; Donmez, Levent; Vural, Tumer; Gunseren, Filiz

    2012-07-01

    The aim of the study was to investigate the distribution of Candida species isolated from urine specimens of hospitalized patients in Akdeniz University Hospital, Antalya, Turkey, as well as their susceptibilities to antifungal agents. A total of 100 patients who had nosocomial candiduria between March 2003 and May 2004 at the facility were included in the study. Organisms were identified by conventional methods and the use of API ID 32C strips. Susceptibilities of the isolates to amphotericin B were determined by Etest, whereas the minimum inhibitory concentration (MIC) values of these same strains to fluconazole, voriconazole and caspofungin were assessed using the broth microdilution method. The most common species recovered was C. albicans 44% of all yeasts, followed by C. tropicalis (20%), C. glabrata (18%), C. krusei (6%), C. famata (5%), C. parapsilosis (4%), C. kefyr (2%) and C. guilliermondii (1%). A total of nine (9%) of the isolates, including five C. krusei and four C. glabrata isolates were susceptible dose-dependent (SDD) to fluconazole. In constrast, only two C. glabrata and one C. krusei isolates were resistant to this antifungal. The voriconazole MICs for all Candida isolates were ≤0.5 μg/ml, except for one C. glabrata isolate with a MIC value of 2 μg/ml. Among all isolates, 94% were susceptible to amphotericin B with MIC values of <1 μg/ml and all isolates were susceptible to caspofungin with MIC values of ≤0.5 μg/ml. Future studies are needed to define better treatment regimens for those patients who have fluconazole-resistant Candida urinary tract infections.

  6. Antifungal Properties of Haem Peroxidase from Acorus calamus

    PubMed Central

    GHOSH, MODHUMITA

    2006-01-01

    • Background and Aims Plants have evolved a number of inducible defence mechanisms against pathogen attack, including synthesis of pathogenesis-related proteins. The aim of the study was to purify and characterize antifungal protein from leaves of Acorus calamus. • Methods Leaf proteins from A. calamus were fractionated by cation exchange chromatography and gel filtration and the fraction inhibiting the hyphal extension of phytopathogens was characterized. The temperature stability and pH optima of the protein were determined and its presence was localized in the leaf tissues. • Key Results The purified protein was identified as a class III haem peroxidase with a molecular weight of approx. 32 kDa and pI of 7·93. The temperature stability of the enzyme was observed from 5 °C to 60 °C with a temperature optimum of 36 °C. Maximum enzyme activity was registered at pH 5·5. The pH and temperature optima were corroborated with the antifungal activity of the enzyme. The enzyme was localized in the leaf epidermal cells and lumen tissues of xylem, characteristic of class III peroxidases. The toxic nature of the enzyme which inhibited hyphal growth was demonstrated against phytopathogens such as Macrophomina phaseolina, Fusarium moniliforme and Trichosporium vesiculosum. Microscopic observations revealed distortion in the hyphal structure with stunted growth, increased volume and extensive hyphal branching. • Conclusions This study indicates that peroxidases may have a role to play in host defence by inhibiting the hyphal extension of invading pathogens. PMID:17056613

  7. Antibacterial, Antifungal and antioxidant activities of some medicinal plants.

    PubMed

    Wazir, Asma; Mehjabeen, -; Jahan, Noor; Sherwani, Sikander Khan; Ahmad, Mansoor

    2014-11-01

    The purpose of this study was to evaluate the antibacterial, antifungal and antioxidant activities of medicinal plants. The antibacterial activity of methanolic extracts of three medicinal plants (Swertia chirata, Terminalia bellerica and Zanthoxylum armatum) were tested against Gentamicin (standard drug) on eleven gram positive and seventeen gram negative bacteria by agar well method. It was revealed that seven-gram negative and six gram positive bacterial species were inhibited by these plant extracts. Minimum inhibitory concentrations (MIC) of the extracts were determined by broth micro-dilution method. The significant MIC value of Swertia chirata was 20mg/ml against Serratia marcesens, Zanthoxylum armatum was 10 mg/ml against Aeromonas hydrophila and Terminali bellerica was 20mg/ml against Acinetobacter baumanii as well as Serratia marcesens. Antifungal screening was done for methanolic extracts of these plants by agar well method with the 6 saprophytic, 5 dermatophytic and 6 yeasts. In this case Griseofulvin was used as a standard. All saprophytes and dermatophytes were showed resistance by these plants extracts except Microsporum canis, which was inhibited by Z. armatum and S. chirata extracts. The significant MIC value of Zanthoxylum armatum was 10mg/ml against Microsporum canis and Swertia chirata was 10mg/ml against Candida tropicalis. The anti-oxidant study was performed by DPPH free radical scavenging assay using ascorbic acid as a reference standard. Significant antioxidant activities were observed by Swertia chirata and Zanthoxylum armatum at concentration 200μg/ml was 70% DPPH scavenging activity (EC50=937.5μg/ml) while Terminalia bellerica showed 55.6% DPPH scavenging activity (EC50=100μg/ml). This study has shown that these plants could provide potent antibacterial compounds and may possible preventive agents in ROS related ailments.

  8. Antifungal properties of silver nanoparticles against indoor mould growth.

    PubMed

    Ogar, Anna; Tylko, Grzegorz; Turnau, Katarzyna

    2015-07-15

    The presence of moulds in indoor environments causes serious diseases and acute or chronic toxicological syndromes. In order to inhibit or prevent the growth of microorganisms on building materials, the disruption of their vital processes or the reduction of reproduction is required. The development of novel techniques that impair the growth of microorganisms on building materials is usually based on silver nanoparticles (AgNPs). It makes them an alternative to other biocides. AgNPs have proven antibacterial activity and became promising in relation to fungi. The aim of the study was to assess growth and morphology of mycelia of typical indoor fungal species: Penicillium brevicompactum, Aspergillus fumigatus, Cladosporium cladosporoides, Chaetomium globosum and Stachybotrys chartarum as well as Mortierella alpina, cultured on agar media. The antifungal activity of AgNPs was also tested in relation to C. globosum and S. chartarum grown on the surface of gypsum drywall. It was found that the presence of AgNPs in concentrations of 30-200mg/l significantly decreased the growth of fungi. However, in the case of M. alpina, AgNPs stimulated its growth. Moreover, strong changes in moulds morphology and colour were observed after administration of AgNPs. Parameters of conidiophores/sporangiophores varied depending on mould region and changed significantly after treatment with AgNPs. The experiments have shown antifungal properties of AgNPs against common indoor mould species. Their application to building materials could effectively protect indoor environments from mould development. However, consideration must be given to the fact that the growth of some fungal strains might be stimulated by AgNPs.

  9. Antifungal Effect of Plant Essential Oils on Controlling Phytophthora Species.

    PubMed

    Amini, Jahanshir; Farhang, Vahid; Javadi, Taimoor; Nazemi, Javad

    2016-02-01

    In this study, antifungal activity of essential oils of Cymbopogon citratus and Ocimum basilicum and two fungicides Mancozeb and Metalaxyl-Mancozeb in six different concentrations were investigated for controlling three species of Phytophthora, including P. capsici, P. drechsleri and P. melonis on pepper, cucumber and melon under in vitro and greenhouse conditions, respectively. Under the in vitro condition, the median effective concen- tration (EC50) values (ppm) of plant essential oils and fungicides were measured. In greenhouse, soil infested with Phytophthora species was treated by adding 50 ml of essential oils and fungicides (100 ppm). Disease severity was determined after 28 days. Among two tested plant essential oils, C. citratus had the lowest EC50 values for inhibition of the mycelial growth of P. capsici (31.473), P. melonis (33.097) and P. drechsleri (69.112), respectively. The mean EC50 values for Metalaxyl-Mancozeb on these pathogens were 20.87, 20.06 and 17.70, respectively. Chemical analysis of plant essential oils by GC-MS showed that, among 42 compounds identified from C. citratus, two compounds β-geranial (α-citral) (39.16%) and z-citral (30.95%) were the most abundant. Under the greenhouse condition, Metalaxyl-Mancozeb caused the greatest reduction in disease severity, 84.2%, 86.8% and 92.1% on melon, cucumber, and pepper, respectively. The C. citratus essential oil reduced disease severity from 47.4% to 60.5% compared to the untreated control (p≤0.05). Essential oils of O. basilicum had the lowest effects on the pathogens under in vitro and greenhouse conditions. These results show that essential oils may contribute to the development of new antifungal agents to protect the crops from Phytophthora diseases.

  10. Antifungal Effect of Plant Essential Oils on Controlling Phytophthora Species

    PubMed Central

    Amini, Jahanshir; Farhang, Vahid; Javadi, Taimoor; Nazemi, Javad

    2016-01-01

    In this study, antifungal activity of essential oils of Cymbopogon citratus and Ocimum basilicum and two fungicides Mancozeb and Metalaxyl-Mancozeb in six different concentrations were investigated for controlling three species of Phytophthora, including P. capsici, P. drechsleri and P. melonis on pepper, cucumber and melon under in vitro and greenhouse conditions, respectively. Under the in vitro condition, the median effective concen- tration (EC50) values (ppm) of plant essential oils and fungicides were measured. In greenhouse, soil infested with Phytophthora species was treated by adding 50 ml of essential oils and fungicides (100 ppm). Disease severity was determined after 28 days. Among two tested plant essential oils, C. citratus had the lowest EC50 values for inhibition of the mycelial growth of P. capsici (31.473), P. melonis (33.097) and P. drechsleri (69.112), respectively. The mean EC50 values for Metalaxyl-Mancozeb on these pathogens were 20.87, 20.06 and 17.70, respectively. Chemical analysis of plant essential oils by GC-MS showed that, among 42 compounds identified from C. citratus, two compounds β-geranial (α-citral) (39.16%) and z-citral (30.95%) were the most abundant. Under the greenhouse condition, Metalaxyl-Mancozeb caused the greatest reduction in disease severity, 84.2%, 86.8% and 92.1% on melon, cucumber, and pepper, respectively. The C. citratus essential oil reduced disease severity from 47.4% to 60.5% compared to the untreated control (p≤0.05). Essential oils of O. basilicum had the lowest effects on the pathogens under in vitro and greenhouse conditions. These results show that essential oils may contribute to the development of new antifungal agents to protect the crops from Phytophthora diseases. PMID:26889111

  11. Quantitative structure-antifungal activity relationships of some benzohydrazides against Botrytis cinerea.

    PubMed

    Reino, José L; Saiz-Urra, Liane; Hernandez-Galan, Rosario; Aran, Vicente J; Hitchcock, Peter B; Hanson, James R; Gonzalez, Maykel Perez; Collado, Isidro G

    2007-06-27

    Fourteen benzohydrazides have been synthesized and evaluated for their in vitro antifungal activity against the phytopathogenic fungus Botrytis cinerea. The best antifungal activity was observed for the N',N'-dibenzylbenzohydrazides 3b-d and for the N-aminoisoindoline-derived benzohydrazide 5. A quantitative structure-activity relationship (QSAR) study has been developed using a topological substructural molecular design (TOPS-MODE) approach to interpret the antifungal activity of these synthetic compounds. The model described 98.3% of the experimental variance, with a standard deviation of 4.02. The influence of an ortho substituent on the conformation of the benzohydrazides was investigated by X-ray crystallography and supported by QSAR study. Several aspects of the structure-activity relationships are discussed in terms of the contribution of different bonds to the antifungal activity, thereby making the relationships between structure and biological activity more transparent.

  12. Current recommendations and importance of antifungal stewardship for the management of invasive candidiasis.

    PubMed

    Miyazaki, Taiga; Kohno, Shigeru

    2015-01-01

    Invasive candidiasis can have a major effect on patient prognosis and medical economics. Quickly eliminating the focus of the infection and administering appropriate antifungal therapy are important. Clinical guidelines for invasive candidiasis have been issued in the USA, Europe and recently in Japan. The purpose of this review is to summarize the current recommendations on how to diagnose and treat invasive candidiasis based on the evidence gathered to date and by referencing guidelines from various countries. Echinocandin antifungals play a central role in the prevention and treatment of invasive candidiasis although a recent increase in echinocandin-resistant Candida glabrata is seen as problematic. In the future, promoting the appropriate use of antifungal agents by antifungal stewardship teams will be necessary to suppress adverse effects, appearance of resistant strains and unnecessary medical expenses, as well as improve positive clinical outcomes and prognoses.

  13. Self-assembled cardanol azo derivatives as antifungal agent with chitin-binding ability.

    PubMed

    Mahata, Denial; Mandal, Santi M; Bharti, Rashmi; Gupta, Vinay Krishna; Mandal, Mahitosh; Nag, Ahindra; Nando, Golok B

    2014-08-01

    Cardanol is a non-isoprenoic phenolic lipid-mixture of distilled cashew nut shell liquid obtained from Anacardium occidentale. Herein, cardanol is purified from cashew nut shell liquid (CNSL) and synthesized to new compounds with different azo amphiphiles. These synthesized compounds are allowed to self-assembled in hydrophobic environment and checked antifungal activity against Candida albicans. Self-assembled structure of CABA showed higher antifungal activity (16μg/mL) and chitin-binding ability in comparison to CAP and CANB. Furthermore, the self-assembled azo amphiphiles are immobilized with silver ions to prepare hydrogel which showed eight folds enhanced antifungal activity. Toxicity is reduced by several folds of self-assembled or hydrogel structure in comparison to pure compounds. Thus, the self-assembled structure of amphiphiles and their hydrogels have been found to be new macromolecules of interest with potential use as antifungal drugs. PMID:24836571

  14. Antifungal Imidazole-Decorated Cationic Amphiphiles with Markedly Low Hemolytic Activity.

    PubMed

    Benhamou, Raphael I; Steinbuch, Kfir B; Fridman, Micha

    2016-08-01

    Herein we report that an imidazole-decorated cationic amphiphile derived from the pseudo-disaccharide nebramine has potent antifungal activity against strains of Candida glabrata pathogens. In combination with the natural bis-benzylisoquinoline alkaloid tetrandrine the reported antifungal cationic amphiphile demonstrated synergistic antifungal activity against Candida albicans pathogens. This unique membrane disruptor caused no detectible mammalian red blood cell hemolysis at concentrations up to more than two orders of magnitude greater than its minimal inhibitory concentrations against the tested C. glabrata strains. We provide evidence that potency against C. glabrata may be associated with differences between the drug efflux pumps of C. albicans and C. glabrata. Imidazole decorated-cationic amphiphiles show promise for the development of less toxic membrane-disrupting antifungal drugs and drug combinations. PMID:27258738

  15. A case of fungal keratitis caused by Scopulariopsis brevicaulis: treatment with antifungal agents and penetrating keratoplasty.

    PubMed Central

    Ragge, N K; Hart, J C; Easty, D L; Tyers, A G

    1990-01-01

    A case of fungal keratitis caused by Scopulariopsis brevicaulis following a penetrating eye injury is described. Treatment with antifungal agents and keratoplasty resulted in a favourable outcome. Images PMID:2168203

  16. Antifungal and antibacterial activity of Haliclona sp. from the Persian Gulf, Iran.

    PubMed

    Nazemi, M; Alidoust Salimi, M; Alidoust Salimi, P; Motallebi, A; Tamadoni Jahromi, S; Ahmadzadeh, O

    2014-09-01

    In this study, antifungal and antibacterial activities of diethyl ether, methanol and aqueous extracts of Haliclona sp. were assessed (in vitro). The antibacterial activity of the extracts was determined by broth dilution methods against clinical Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa and Gram-positive bacteria: Staphylococcus aureus aureus, Bacillus subtilis spizizenii. The antifungal activity of the extracts was determined by using a broth microdilution test against clinical fungi Candida albicans and Aspergillus fumigatus. Our results showed diethyl ether extract of Haliclona sp. was active on Gram-positive bacteria. In addition, methanol extract in comparison with diethyl ether extract had better activity against C. albicans (MIC: 0.75 mg/mL, MFC: 1.5mg/mL) and A. fumigatus (MIC: 2mg/mL, MFC: 3mg/mL). Aqueous extract had neither antifungal nor antibacterial activities. Based our results, Haliclona sp. can be considered as a source of novel antibiotic and antifungal.

  17. Mode of Action for Reproductive and Hepatic Toxicity Inferred from a Genomic Study of Triazole Antifungals

    EPA Science Inventory

    The mode of action for the reproductive toxicity of triazole antifungals have been previously characterized by an observed increased in serum testosterone, hepatotoxicity, and reduced insemination and fertility indices. In order to refine our mechanistic understanding of these m...

  18. Synergy and antagonism between iron chelators and antifungal drugs in Cryptococcus.

    PubMed

    Lai, Yu-Wen; Campbell, Leona T; Wilkins, Marc R; Pang, Chi Nam Ignatius; Chen, Sharon; Carter, Dee A

    2016-10-01

    Fungal infections remain very difficult to treat, and developing new antifungal drugs is difficult and expensive. Recent approaches therefore seek to augment existing antifungals with synergistic agents that can lower the therapeutic dose, increase efficacy and prevent resistance from developing. Iron limitation can inhibit microbial growth, and iron chelators have been employed to treat fungal infections. In this study, chequerboard testing was used to explore combinations of iron chelators with antifungal agents against pathogenic Cryptococcus spp. with the aim of determining how disruption to iron homeostasis affects antifungal susceptibility. The iron chelators ethylenediaminetetraacetic acid (EDTA), deferoxamine (DFO), deferiprone (DFP), deferasirox (DSX), ciclopirox olamine and lactoferrin (LF) were paired with the antifungal agents amphotericin B (AmB), fluconazole, itraconazole, voriconazole and caspofungin. All chelators except for DFO increased the efficacy of AmB, and significant synergy was seen between AmB and LF for all Cryptococcus strains. Addition of exogenous iron rescued cells from the antifungal effect of LF alone but could not prevent inhibition by AmB + LF, indicating that synergy was not due primarily to iron chelation but to other properties of LF that were potentiated in the presence of AmB. Significant synergy was not seen consistently for other antifungal-chelator combinations, and EDTA, DSX and DFP antagonised the activity of azole drugs in strains of Cryptococcus neoformans var. grubii. This study highlights the range of interactions that can be induced by chelators and indicates that most antifungal drugs are not enhanced by iron limitation in Cryptococcus. PMID:27474467

  19. Characterization of Tamoxifen as an Antifungal Agent Using the Yeast Schizosaccharomyces Pombe Model Organism.

    PubMed

    Zhang, Xibo; Fang, Yue; Jaiseng, Wurentuya; Hu, Lingling; Lu, Yabin; Ma, Yan; Furuyashiki, Tomoyuki

    2015-01-01

    Tamoxifen, a selective estrogen receptor modulator used for managing breast cancer, is known to have antifungal activity. However, its molecular mechanism remains unknown. Using the fission yeast Schizosaccharomyces pombe as a model organism, we have explored the mechanism involved in antifungal action of tamoxifen. Since tamoxifen was shown to inhibit the binding of calmodulin to calcineurin in fungi, we first examined involvement of these molecules and found that overexpression of a catalytic subunit of calcineurin and its constitutively active mutant as well as calmodulin increases tamoxifen sensitivity. Since terbinafine and azoles inhibit enzymes for ergosterol biosynthesis, Erg1 and Erg11, for their antifungal actions, we also examined involvement of these molecules. Overexpression of Erg1 and Erg11 reduced the sensitivity to terbinafine and azoles, respectively, but increased tamoxifen sensitivity, suggesting that ergosterol biosynthesis is differently related to the action of tamoxifen and those of terbinafine and azoles. To elucidate molecules involved in tamoxifen action, we performed a genome-wide screen for altered sensitivity to tamoxifen using a fission yeast gene deletion library, and identified various hypersensitive and resistant mutants to this drug. Notably, these mutants are rarely overlapped with those identified in similar genetic screens with currently used antifungals, suggesting a novel mode of antifungal action. Furthermore, tamoxifen augmented antifungal actions of terbinafine and azoles, suggesting synergetic actions between these drugs. Therefore, our findings suggest that calmodulin-calcineurin pathway and ergosterol biosynthesis are related to antifungal action of tamoxifen, and propose novel targets for antifungal development as well as combined therapy with tamoxifen for fungal diseases.

  20. Characterization of Tamoxifen as an Antifungal Agent Using the Yeast Schizosaccharomyces Pombe Model Organism.

    PubMed

    Zhang, Xibo; Fang, Yue; Jaiseng, Wurentuya; Hu, Lingling; Lu, Yabin; Ma, Yan; Furuyashiki, Tomoyuki

    2015-01-01

    Tamoxifen, a selective estrogen receptor modulator used for managing breast cancer, is known to have antifungal activity. However, its molecular mechanism remains unknown. Using the fission yeast Schizosaccharomyces pombe as a model organism, we have explored the mechanism involved in antifungal action of tamoxifen. Since tamoxifen was shown to inhibit the binding of calmodulin to calcineurin in fungi, we first examined involvement of these molecules and found that overexpression of a catalytic subunit of calcineurin and its constitutively active mutant as well as calmodulin increases tamoxifen sensitivity. Since terbinafine and azoles inhibit enzymes for ergosterol biosynthesis, Erg1 and Erg11, for their antifungal actions, we also examined involvement of these molecules. Overexpression of Erg1 and Erg11 reduced the sensitivity to terbinafine and azoles, respectively, but increased tamoxifen sensitivity, suggesting that ergosterol biosynthesis is differently related to the action of tamoxifen and those of terbinafine and azoles. To elucidate molecules involved in tamoxifen action, we performed a genome-wide screen for altered sensitivity to tamoxifen using a fission yeast gene deletion library, and identified various hypersensitive and resistant mutants to this drug. Notably, these mutants are rarely overlapped with those identified in similar genetic screens with currently used antifungals, suggesting a novel mode of antifungal action. Furthermore, tamoxifen augmented antifungal actions of terbinafine and azoles, suggesting synergetic actions between these drugs. Therefore, our findings suggest that calmodulin-calcineurin pathway and ergosterol biosynthesis are related to antifungal action of tamoxifen, and propose novel targets for antifungal development as well as combined therapy with tamoxifen for fungal diseases. PMID:26628015

  1. Stilbene derivatives with antifungal and radical scavenging properties from the stem bark of Artocarpus nobilis.

    PubMed

    Jayasinghe, U L B; Puvanendran, S; Hara, N; Fujimoto, Y

    2004-12-01

    Antifungal activity-guided fractionation of the n-butanol extract from the methanol extract of the stem bark of Artocarpus nobilis furnished two stilbene derivatives (E)-4-isopentenyl-3,5,2',4'-tetrahydroxystilbene and (E)-4-(3-methyl-E-but-1-enyl)-3,5,2',4'-tetrahydroxystilbene. Both compounds showed strong antifungal activity against Cladosporium cladosporioides and high radical scavenging activity towards the DPPH radical in TLC bio-autography method.

  2. Antibiotics from basidiomycetes. 26. Phlebiakauranol aldehyde an antifungal and cytotoxic metabolite from Punctularia atropurpurascens.

    PubMed

    Anke, H; Casser, I; Steglich, W; Pommer, E H

    1987-04-01

    Phlebiakauranol aldehyde and the corresponding alcohol were isolated from cultures of Punctularia atropurpurascens. The aldehyde but not the alcohol exhibited strong antifungal activity against several phytopathogens as well as antibacterial and cytotoxic activities. Two acetylated derivatives prepared from the aldehyde showed only very weak antifungal and antibacterial and moderate cytotoxic activities. We therefore assume, that the aldehyde group together with the high number of hydroxyl groups are responsible for the biological activity of the compound.

  3. In vitro antifungal susceptibility of Malassezia pachydermatis from dogs with and without skin lesions.

    PubMed

    Cafarchia, Claudia; Figueredo, Luciana A; Iatta, Roberta; Montagna, Maria Teresa; Otranto, Domenico

    2012-03-23

    Canine Malassezia dermatitis is frequently treated with systemic ketoconazole (KTZ) and itraconazole (ITZ). However, no information is available on the antifungal susceptibility to azoles and allilamine of Malassezia pachydermatis isolates from dogs with or without skin lesions. The present study was designed to evaluate the in vitro antifungal susceptibility of M. pachydermatis strains from dogs with or without skin lesions to KTZ, ITZ, miconazole (MICO), fluconazole (FLZ), posaconazole (POS), voriconazole (VOR) and terbinafine (TER) using the Clinical and Laboratory Standards Institute reference Broth Microdilution Method (CLSI M27-A2). The association between the susceptibility to antifungal compounds and the origin of M. pachydermatis, from skin with or without lesions has been also assessed. A total of 62 M. pachydermatis strains from healthy dogs (i.e., Group A=30) or with skin lesions (i.e., Group B=32) were tested. ITZ, KTZ and POS showed the highest activity against M. pachydermatis strains, whereas MICO TER and FLZ the lowest. A higher number of Malassezia resistant strains were registered among isolates from Group B than those from Group A. This study indicates that M. pachydermatis strains were susceptible to ITZ, KTZ, and POS. However, dogs with lesions may harbour strains with low susceptibility to antifungal agents and displaying cross-resistance phenomena to azole. The antifungal therapy in Malassezia infections requires careful appraisal of choice of drugs especially in cases of unresponsiveness to antifungal treatment or recurrent infections. PMID:21962411

  4. Preparation, characterization, and antifungal activity of hymexazol-linked chitosan derivatives

    NASA Astrophysics Data System (ADS)

    Li, Yan; Qin, Yukun; Liu, Song; Li, Pengcheng; Xing, Rong'e.

    2016-09-01

    In this study, three hymexazol-linked chitosan derivatives (HML-CS) were synthesized and their structures confirmed by Fourier transform infrared and elemental analysis. Linkage ratios were measured by high performance liquid chromatography. The derivatives' antifungal activity against the plant pathogenic fungi Rhizoctonia solani CGMCC 3.28 and Gibberella zeae CGMCC 3.42 were investigated at concentrations of 100, 200, and 400 mg/L. These HML-CS derivatives exhibited stronger antifungal activity than CS alone. HML-CS-1 showed the best antifungal activity against G. zeae, whose antifungal index was 65.9% at 400 mg/L, and also showed the best antifungal activity against R. solani, whose antifungal index was 52.7% at 400 mg/L. This conjugation of CS and HML suggested the presence of synergistic effects between the moieties and indicated that these derivatives possessed great potential as novel fungicides and require further research for the development of applications in crop protection.

  5. Synthesis of Natural Acylphloroglucinol-Based Antifungal Compounds against Cryptococcus Species.

    PubMed

    Yu, Qian; Ravu, Ranga Rao; Jacob, Melissa R; Khan, Shabana I; Agarwal, Ameeta K; Yu, Bo-Yang; Li, Xing-Cong

    2016-09-23

    Thirty-three natural-product-based acylphloroglucinol derivatives were synthesized to identify antifungal compounds against Cryptococcus spp. that cause the life-threatening disseminated cryptococcosis. In vitro antifungal testing showed that 17 compounds were active against C. neoformans ATCC 90113, C. neoformans H99, and C. gattii ATCC 32609, with minimum inhibitory concentrations (MICs) in the range 1.0-16.7 μg/mL. Analysis of the structure and antifungal activity of these compounds indicated that the 2,4-diacyl- and 2-acyl-4-alkylphloroglucinols were more active than O-alkyl-acylphloroglucinols. The most promising compound found was 2-methyl-1-(2,4,6-trihydroxy-3-(4-isopropylbenzyl)phenyl)propan-1-one (11j), which exhibited potent antifungal activity (MICs, 1.5-2.1 μg/mL) and low cytotoxicity against the mammalian Vero and LLC-PK1 cell lines (IC50 values >50 μg/mL). This compound may serve as a template for further synthesis of new analogues with improved antifungal activity. The findings of the present work may contribute to future antifungal discovery toward pharmaceutical development of new treatments for cryptococcosis. PMID:27584935

  6. Isavuconazole: Pharmacology, Pharmacodynamics, and Current Clinical Experience with a New Triazole Antifungal Agent.

    PubMed

    Rybak, Jeffrey M; Marx, Kayleigh R; Nishimoto, Andrew T; Rogers, P David

    2015-11-01

    Coinciding with the continually increasing population of immunocompromised patients worldwide, the incidence of invasive fungal infections has grown over the past 4 decades. Unfortunately, infections caused by both yeasts such as Candida and molds such as Aspergillus or Mucorales remain associated with unacceptably high morbidity and mortality. In addition, the available antifungals with proven efficacy in the treatment of these infections remain severely limited. Although previously available second-generation triazole antifungals have significantly expanded the spectrum of the triazole antifungal class, these agents are laden with shortcomings in their safety profiles as well as formulation and pharmacokinetic challenges. Isavuconazole, administered as the prodrug isavuconazonium, is the latest second-generation triazole antifungal to receive U.S. Food and Drug Administration approval. Approved for the treatment of both invasive aspergillosis and invasive mucormycosis, and currently under investigation for the treatment of candidemia and invasive candidiasis, isavuconazole may have therapeutic advantages over its predecessors. With clinically relevant antifungal potency against a broad range of yeasts, dimorphic fungi, and molds, isavuconazole has a spectrum of activity reminiscent of the polyene amphotericin B. Moreover, clinical experience thus far has revealed isavuconazole to be associated with fewer toxicities than voriconazole, even when administered without therapeutic drug monitoring. These characteristics, in an agent available in both a highly bioavailable oral and a β-cyclodextrin-free intravenous formulation, will likely make isavuconazole a welcome addition to the triazole class of antifungals.

  7. Antagonism of antifungal metabolites from Streptomyces griseus H7602 against Phytophthora capsici.

    PubMed

    Nguyen, Xuan Hoa; Naing, Kyaw Wai; Lee, Young Seong; Kim, Yong Hwan; Moon, Jae Hak; Kim, Kil Yong

    2015-01-01

    In this study, evidences for antagonism were established by production of antifungal metabolites from Streptomyces griseus H7602, which were active to inhibit mycelial growth of Phytophthora capsici in the in vitro assays. Mycelial growth and zoosporangia formation of P. capsici was strongly inhibited in the medium containing the cell free culture filtrate of S. griseus H7602. Antifungal metabolites from the cell free culture filtrate of S. griseus H7602 showed substantial antagonistic effects on P. capsici. In addition, a purified antifungal compound was separated from the antifungal metabolites of S. griseus H7602 and identified to be 1H-pyrrole-2-carboxylic acid (PCA) by spectra analyses. PCA showed strong antifungal activity and was evaluated for the first time for its antagonism against P. capsici under in vitro conditions. Minimum inhibitory concentration (MIC) value of PCA was low (4 µg ml(-1)), and the mycelial growth of P. capsici was almost inhibited at concentration of 64 µg ml(-1). This study suggests that the PCA may be useful as biofungicides against P. capsici, and the prominent antagonism of antifungal metabolites from S. griseus H7602 highlights it as a candidate for biocontrol of P. capsici.

  8. In vitro antifungal activity and probable fungicidal mechanism of aqueous extract of Barleria grandiflora.

    PubMed

    Kumari, Suman; Jain, Preeti; Sharma, Bhawana; Kadyan, Preeti; Dabur, Rajesh

    2015-04-01

    Barleria grandiflora Dalz. (Acanthaceae) is being used in India to treat different types of disorders including skin infections. Therefore, there are good possibilities to find antifungal compounds in its extracts with novel mechanism of action. The main objectives of the present study were to evaluate the antifungal activity of plant extracts and to study its effects on metabolic pathways of A. fumigatus. The microbroth dilution assay was used to explore antifungal activity and MIC of various extracts. Metabolic profiles of control and treated cultures were collected from Q-TOF-MS interfaced with HPLC. Affected metabolic pathways of A. fumigatus after the treatment were analyzed by discrimination analysis of mass data. Antifungal activities were observed in hot and cold water extracts of the plant. Hot water extract of B. grandiflora showed significant activity against tested fungi in the range 0.625-1.25 mg/mL. Partial least discrimination analysis revealed that the hot water plant extract downregulated amino acid, glyoxylate pathway, and methylcitrate pathways at the same time due to the synergistic effects of secondary metabolites. Hot water extract also downregulated several other metabolic pathways unique to fungi indicating its specific activity toward fungi. B. grandiflora showed promising antifungal activity which can further be exploited by identification of active compounds, to inhibit the specific fungal pathways and development of novel therapeutic antifungal drugs. PMID:25672323

  9. Candida tropicalis Antifungal Cross-Resistance Is Related to Different Azole Target (Erg11p) Modifications

    PubMed Central

    Forastiero, A.; Mesa-Arango, A. C.; Alastruey-Izquierdo, A.; Alcazar-Fuoli, L.; Bernal-Martinez, L.; Pelaez, T.; Lopez, J. F.; Grimalt, J. O.; Gomez-Lopez, A.; Cuesta, I.; Zaragoza, O.

    2013-01-01

    Candida tropicalis ranks between third and fourth among Candida species most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives. Candida tropicalis is usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However, C. tropicalis resistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resistance mechanisms operating in C. tropicalis strains isolated from clinical samples showing resistance to azole drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal drug resistance was related to mutations of the azole target (Erg11p) with or without alterations of the ergosterol biosynthesis pathway. The antifungal drug resistance shown in vitro correlated very well with the results obtained in vivo using the model host Galleria mellonella. Using this panel of strains, the G. mellonella model system was validated as a simple, nonmammalian minihost model that can be used to study in vitro-in vivo correlation of antifungals in C. tropicalis. The development in C. tropicalis of antifungal drug resistance with different mechanisms during antifungal treatment has potential clinical impact and deserves specific prospective studies. PMID:23877676

  10. Isolation, characterization and antifungal docking studies of wortmannin isolated from Penicillium radicum

    PubMed Central

    Singh, Vineeta; Praveen, Vandana; Tripathi, Divya; Haque, Shafiul; Somvanshi, Pallavi; Katti, S. B.; Tripathi, C. K. M.

    2015-01-01

    During the search for a potent antifungal drug, a cell-permeable metabolite was isolated from a soil isolate taxonomically identified as Penicillium radicum. The strain was found to be a potent antifungal agent. Production conditions of the active compound were optimized and the active compound was isolated, purified, characterized and identified as a phosphoinositide 3-kinase (PI3K) inhibitor, commonly known as wortmannin (Wtmn). This is very first time we are reporting the production of Wtmn from P. radicum. In addition to its previously discovered anticancer properties, the broad spectrum antifungal property of Wtmn was re-confirmed using various fungal strains. Virtual screening was performed through molecular docking studies against potential antifungal targets, and it was found that Wtmn was predicted to impede the actions of these targets more efficiently than known antifungal compounds such as voriconazole and nikkomycin i.e. 1) mevalonate-5-diphosphate decarboxylase (1FI4), responsible for sterol/isoprenoid biosynthesis; 2) exocyst complex component SEC3 (3A58) where Rho- and phosphoinositide-dependent localization is present and 3) Kre2p/Mnt1p a Golgi alpha1,2-mannosyltransferase (1S4N) involved in the biosynthesis of yeast cell wall glycoproteins). We conclude that Wtmn produced from P. radicum is a promising lead compound which could be potentially used as an efficient antifungal drug in the near future after appropriate structural modifications to reduce toxicity and improve stability. PMID:26159770

  11. In vitro antifungal activity and mechanism of essential oil from fennel (Foeniculum vulgare L.) on dermatophyte species.

    PubMed

    Zeng, Hong; Chen, Xinping; Liang, Jingnan

    2015-01-01

    Fennel seed essential oil (FSEO) is a plant-derived natural therapeutic against dermatophytes. In this study, the antifungal effects of FSEO were investigated from varied aspects, such as MIC and minimum fungicidal concentration, mycelia growth, spore germination and biomass. The results indicated that FSEO had potent antifungal activities on Trichophyton rubrum ATCC 40051, Trichophyton tonsurans 10-0400, Microsporum gypseum 44693-1 and Trichophyton mentagrophytes 10-0060, which is better than the commonly used antifungal agents fluconazole and amphotericin B. Flow cytometry and transmission electron microscopy experiments suggested that the antifungal mechanism of FSEO was to damage the plasma membrane and intracellular organelles. Further study revealed that it could also inhibit the mitochondrial enzyme activities, such as succinate dehydrogenase, malate dehydrogenase and ATPase. With better antifungal activity than the commonly used antifungal agents and less possibility of inducing drug resistance, FSEO could be used as a potential antidermatophytic agent.

  12. In vitro antifungal activity and mechanism of essential oil from fennel (Foeniculum vulgare L.) on dermatophyte species.

    PubMed

    Zeng, Hong; Chen, Xinping; Liang, Jingnan

    2015-01-01

    Fennel seed essential oil (FSEO) is a plant-derived natural therapeutic against dermatophytes. In this study, the antifungal effects of FSEO were investigated from varied aspects, such as MIC and minimum fungicidal concentration, mycelia growth, spore germination and biomass. The results indicated that FSEO had potent antifungal activities on Trichophyton rubrum ATCC 40051, Trichophyton tonsurans 10-0400, Microsporum gypseum 44693-1 and Trichophyton mentagrophytes 10-0060, which is better than the commonly used antifungal agents fluconazole and amphotericin B. Flow cytometry and transmission electron microscopy experiments suggested that the antifungal mechanism of FSEO was to damage the plasma membrane and intracellular organelles. Further study revealed that it could also inhibit the mitochondrial enzyme activities, such as succinate dehydrogenase, malate dehydrogenase and ATPase. With better antifungal activity than the commonly used antifungal agents and less possibility of inducing drug resistance, FSEO could be used as a potential antidermatophytic agent. PMID:25351709

  13. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus...

  14. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus...

  15. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus...

  16. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus...

  17. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... citations affecting § 180.443, see the List of CFR Sections Affected, which appears in the Finding Aids... Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus...

  18. [Antifungal activity of essential oils and their constituents against Candida spp. and their effects on activity of amphotericin B].

    PubMed

    Nozaki, Akiko; Takahashi, Eizo; Okamoto, Keinosuke; Ito, Hideyuki; Hatano, Tsutomu

    2010-06-01

    Candidiasis is a common opportunistic fungal infection that responds well to amphotericin B (AMPH) treatment. However, AMPH often causes adverse effects such as kidney injury and hypokalemia. Because some essential oils have been reported to have antifungal effects, we investigated the antifungal activity of various essential oils and their major constituents against Candida spp. Most essential oils examined in this study showed antifungal activity, and several enhanced the antifungal effect of AMPH. Clove oil in particular, and its major constituent eugenol, had potent effects. These findings suggest that combining certain essential oils or their constituents with AMPH may be useful for suppressing the adverse effects of AMPH treatment. PMID:20519869

  19. Searching new antifungals: The use of in vitro and in vivo methods for evaluation of natural compounds.

    PubMed

    Scorzoni, Liliana; Sangalli-Leite, Fernanda; de Lacorte Singulani, Junya; de Paula E Silva, Ana Carolina Alves; Costa-Orlandi, Caroline Barcelos; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares

    2016-04-01

    In the last decades, the increased number of immunocompromised patients has led to the emergence of many forms of fungal infections. Furthermore, there are a restricted arsenal of antifungals available and an increase in the development of resistance to antifungal drugs. Because of these disadvantages, the search for new antifungal agents in natural sources has increased. The development of these new antifungal drugs involves various steps and methodologies. The evaluation of the in vitro antifungal activity and cytotoxicity are the first steps in the screening. There is also the possibility of antifungal combinations to improve the therapy and reduce toxicity. Despite that, the application of the new antifungal candidate could be used in association with photodynamic therapy or using nanotechnology as an ally. In vivo tests can be performed to evaluate the efficacy and toxicity using conventional and alternative animal models. In this work, we review the methods available for the evaluation of the antifungal activity and safety of natural products, as well as the recent advances of new technology in the application of natural products for antifungal therapy.

  20. Clinical evaluation of a frozen commercially prepared microdilution panel for antifungal susceptibility testing of seven antifungal agents, including the new triazoles posaconazole, ravuconazole, and voriconazole.

    PubMed

    Pfaller, M A; Diekema, D J; Messer, S A; Boyken, L; Huynh, H; Hollis, R J

    2002-05-01

    A commercially prepared frozen broth microdilution panel (Trek Diagnostic Systems, Westlake, Ohio) was compared with a reference microdilution panel for antifungal susceptibility testing of two quality control (QC) strains and 99 clinical isolates of Candida spp. The antifungal agents tested included amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, ravuconazole, and voriconazole. Microdilution testing was performed according to NCCLS recommendations. MIC endpoints were read visually after 48 h of incubation and were assessed independently for each microdilution panel. The MICs for the QC strains were within published limits for both the reference and Trek microdilution panels. Discrepancies among MIC endpoints of no more than 2 dilutions were used to calculate the percent agreement. Acceptable levels of agreement between the Trek and reference panels were observed for all antifungal agents tested against the 99 clinical isolates. The overall agreement for each antifungal agent ranged from 96% for ravuconazole to 100% for amphotericin B. The Trek microdilution panel appears to be a viable alternative to frozen microdilution panels prepared in-house. PMID:11980944

  1. In vitro antifungal susceptibility testing of Scopulariopsis brevicaulis strains using agar diffusion method.

    PubMed

    Skóra, Magdalena; Macura, Anna B

    2011-01-01

    The genus Scopulariopsis is a common soil saprotroph and has been isolated from air, organic waste and also from plant, animal and human tissues. Scopulariopsis has mainly been associated in humans with superficial mycoses, but it has also been described as the cause of subcutaneous and invasive infections. The most common aetiological agent of infections in humans is Scopulariopsis brevicaulis. This species has been reported to be resistant in vitro to broad-spectrum antifungal agents available today. The aim of the study was to establish in vitro antifungal susceptibility of 35 S. brevicaulis strains against amphotericin B (AMB), flucytosine (FC), caspofungin (CAS), terbinafine (TER), ciclopirox (CIC), voriconazole (VOR), clotrimazole (CTR), miconazole (MCZ), econazole (ECO), ketoconazole (KET), itraconazole (ITR), and fluconazole (FLU). Antifungal susceptibility tests were evaluated by an agar diffusion method (Neo-Sensitabs, Rosco, Denmark). AMB, FC, CAS, ITR and FLU showed no antifungal activity against S. brevicaulis. TER, CIC, CTR, KET, VOR, ECO, and MCZ revealed inhibitory activity for S. brevicaulis, but it varied for each of the drugs. The best antifungal effect was observed for TER and CIC. All isolates had large inhibition zones for TER and CIC. CTR was also inhibitory for all tested S. brevicaulis isolates, but the diameters of inhibition zones were smaller than for TER and CIC. Nearly 89% isolates showed inhibition zones for KET and the mean diameter of the inhibition zone was comparable to CTR. The least antifungal activity exhibited VQR, ECO and MCZ. Because of the multiresistance of S. brevicaulis, infections due to this species may not respond to particular antifungal treatment and other therapeutic approaches should be considered, e.g., combined therapy and/or surgery. PMID:21682097

  2. In vitro antifungal susceptibility testing of Scopulariopsis brevicaulis strains using agar diffusion method.

    PubMed

    Skóra, Magdalena; Macura, Anna B

    2011-01-01

    The genus Scopulariopsis is a common soil saprotroph and has been isolated from air, organic waste and also from plant, animal and human tissues. Scopulariopsis has mainly been associated in humans with superficial mycoses, but it has also been described as the cause of subcutaneous and invasive infections. The most common aetiological agent of infections in humans is Scopulariopsis brevicaulis. This species has been reported to be resistant in vitro to broad-spectrum antifungal agents available today. The aim of the study was to establish in vitro antifungal susceptibility of 35 S. brevicaulis strains against amphotericin B (AMB), flucytosine (FC), caspofungin (CAS), terbinafine (TER), ciclopirox (CIC), voriconazole (VOR), clotrimazole (CTR), miconazole (MCZ), econazole (ECO), ketoconazole (KET), itraconazole (ITR), and fluconazole (FLU). Antifungal susceptibility tests were evaluated by an agar diffusion method (Neo-Sensitabs, Rosco, Denmark). AMB, FC, CAS, ITR and FLU showed no antifungal activity against S. brevicaulis. TER, CIC, CTR, KET, VOR, ECO, and MCZ revealed inhibitory activity for S. brevicaulis, but it varied for each of the drugs. The best antifungal effect was observed for TER and CIC. All isolates had large inhibition zones for TER and CIC. CTR was also inhibitory for all tested S. brevicaulis isolates, but the diameters of inhibition zones were smaller than for TER and CIC. Nearly 89% isolates showed inhibition zones for KET and the mean diameter of the inhibition zone was comparable to CTR. The least antifungal activity exhibited VQR, ECO and MCZ. Because of the multiresistance of S. brevicaulis, infections due to this species may not respond to particular antifungal treatment and other therapeutic approaches should be considered, e.g., combined therapy and/or surgery.

  3. Antiproliferative effect and characterization of a novel antifungal peptide derived from human Chromogranin A

    PubMed Central

    LI, RUI-FANG; LU, YA-LI; LU, YAN-BO; ZHANG, HUI-RU; HUANG, LIANG; YIN, YANLI; ZHANG, LIN; LIU, SHUAI; LU, ZHIFANG; SUN, YANAN

    2015-01-01

    CGA-N46 is a novel antifungal peptide derived from the N-terminus of human Chromogranin A, corresponding to the 31st to 76th amino acids. Further research on its activities and characteristics may be helpful for the application of CGA-N46 in medical or other situations. In the present study, the antifungal spectrum and physicochemical characteristics of CGA-N46 were investigated using an antifungal assay, its antiproliferative effects on cancer and normal cells were assessed using MTT assay and its combinatorial effect with other antibiotics was analyzed using checkerboard analysis. The results showed that CGA-N46 exhibited antifungal activity against the tested Candidas (C. glabrata, C. parapsilosis, C. krusei, C. tropicalis and C. albicans) at a concentration of <0.8 mM, but had no effect on the growth of filamentous fungi or other types of fungi (Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Fusarium moniliforme, Microsporum canis, Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes), even at a concentration of 3.2 mM. CGA-N46 had an inhibitory effect on the proliferation of lung cancer A549 cells and a reversible effect on the growth of normal primary chicken embryo fibroblast cells, but no hemolytic activity on human erythrocytes at the minimum inhibitory concentration of CGA-N46 against yeasts. The antifungal activity of CGA-N46 was stable at a temperature <40°C or within a broad pH range (pH 5.0–7.0). Its antifungal activity was enhanced when the peptide was used in combination with fluconazole and terbinafine. The present results indicate that CGA-N46 is a safe, physicochemically stable, antifungal peptide with anticancer cell activity that exhibits an additive effect with conventional antibiotics. PMID:26668630

  4. Screening of Pharmacologically Active Small Molecule Compounds Identifies Antifungal Agents Against Candida Biofilms

    PubMed Central

    Watamoto, Takao; Egusa, Hiroshi; Sawase, Takashi; Yatani, Hirofumi

    2015-01-01

    Candida species have emerged as important and common opportunistic human pathogens, particularly in immunocompromised individuals. The current antifungal therapies either have toxic side effects or are insufficiently effect. The aim of this study is develop new small-molecule antifungal compounds by library screening methods using Candida albicans, and to evaluate their antifungal effects on Candida biofilms and cytotoxic effects on human cells. Wild-type C. albicans strain SC5314 was used in library screening. To identify antifungal compounds, we screened a small-molecule library of 1,280 pharmacologically active compounds (LOPAC1280TM) using an antifungal susceptibility test (AST). To investigate the antifungal effects of the hit compounds, ASTs were conducted using Candida strains in various growth modes, including biofilms. We tested the cytotoxicity of the hit compounds using human gingival fibroblast (hGF) cells to evaluate their clinical safety. Only 35 compounds were identified by screening, which inhibited the metabolic activity of C. albicans by >50%. Of these, 26 compounds had fungistatic effects and nine compounds had fungicidal effects on C. albicans. Five compounds, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate, ellipticine and CV-3988, had strong fungicidal effects and could inhibit the metabolic activity of Candida biofilms. However, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine were cytotoxic to hGF cells at low concentrations. CV-3988 showed no cytotoxicity at a fungicidal concentration. Four of the compounds identified, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine, had toxic effects on Candida strains and hGF cells. In contrast, CV-3988 had fungicidal effects on Candida strains, but low cytotoxic effects on hGF cells. Therefore, this screening reveals agent, CV-3988 that was previously unknown to be antifungal agent, which could be a novel therapies for superficial mucosal candidiasis. PMID

  5. Antifungal and antibacterial activities of Petroselinum crispum essential oil.

    PubMed

    Linde, G A; Gazim, Z C; Cardoso, B K; Jorge, L F; Tešević, V; Glamoćlija, J; Soković, M; Colauto, N B

    2016-07-29

    Parsley [Petroselinum crispum (Mill.) Fuss] is regarded as an aromatic, culinary, and medicinal plant and is used in the cosmetic, food, and pharmaceutical industries. However, few studies with conflicting results have been conducted on the antimicrobial activity of parsley essential oil. In addition, there have been no reports of essential oil obtained from parsley aerial parts, except seeds, as an alternative natural antimicrobial agent. Also, microorganism resistance is still a challenge for health and food production. Based on the demand for natural products to control microorganisms, and the re-evaluation of potential medicinal plants for controlling diseases, the objective of this study was to determine the chemical composition and antibacterial and antifungal activities of parsley essential oil against foodborne diseases and opportunistic pathogens. Seven bacteria and eight fungi were tested. The essential oil major compounds were apiol, myristicin, and b-phellandrene. Parsley essential oil had bacteriostatic activity against all tested bacteria, mainly Staphylococcus aureus, Listeria monocytogenes, and Salmonella enterica, at similar or lower concentrations than at least one of the controls, and bactericidal activity against all tested bacteria, mainly S. aureus, at similar or lower concentrations than at least one of the controls. This essential oil also had fungistatic activity against all tested fungi, mainly, Penicillium ochrochloron and Trichoderma viride, at lower concentrations than the ketoconazole control and fungicidal activity against all tested fungi at higher concentrations than the controls. Parsley is used in cooking and medicine, and its essential oil is an effective antimicrobial agent.

  6. Antifungal activity of 4-substituted crotonic acid esters.

    PubMed

    Gershon, H; Shanks, L; Gawiak, D E

    1976-08-01

    Twenty-three 4-substituted crotonic acid esters were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes. For the analogues of the methyl ester containing substituents in the 4 position, the following order of fungitoxicity was observed: I greater than Br greater than Cl greater than CH3S greater than CH3O greater than F=H. Of the homologues of the esters of the 4-iodo and 4-bromo compounds which included methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl, ethyl 4-iodocrotonate was most toxic to the four fungi at pH 7.0 in the presence of 10% beef serum (C. albicans, 18mug/ml, A. niger, 40 mug/ml, M. mucedo, 5 mug/ml, T. mentagrophytes, 4 mug/ml). It is believed that the mechanism of fungitoxicity is due, in part, to a nucleophilic reaction involving SH-containing compounds. This is based on the correlation of fungitoxicity with the order of leaving groups in the nucleophilic reaction and the protection against the toxicity of the test compounds to the fungi by cysteine and glutathione.

  7. Synthesis and antifungal activities of novel polyheterocyclic spirooxindole derivatives.

    PubMed

    Wu, Jia-Shou; Zhang, Xue; Zhang, Ying-Lao; Xie, Jian-Wu

    2015-05-01

    A series of spirooxindole tetrahydrofuran derivatives 3 were obtained in moderate to good yields via oxindole derivatives 1 and β-arylacrylonitrile derivatives 2via base-mediated cascade [3 + 2] double Michael reactions under mild conditions and the application of this method in the synthesis of bioactive analogues, such as functionalized spirooxindole octahydrofuro[3,4-c]pyridine derivatives 4 which contain two new heterocyclic rings and two quaternary carbon centers, has also been developed. Subsequently, antifungal activities of all of the synthesized compounds were evaluated against five phytopathogenic fungi (Rhizoctonia solani, Fusarium semitectum, Alternaria solani, Valsa mali and Fusarium graminearum) using the mycelium growth rate method. The preliminary results showed that the spirooxindole octahydrofuro[3,4-c]pyridine derivative 4 showed higher growth inhibition of Valsa mali and Fusarium graminearum, than spirooxindole tetrahydrofuran derivatives 3. For example, spirooxindole octahydrofuro[3,4-c]pyridine derivative 4ab, having a bromine atom at the meta position of the benzene ring, was the best compound in inhibiting F. g. with an IC50 value of 3.31, in particular with inhibition of 4ab on F. g. being similar to that of the control cycloheximide (IC50 = 3.3 μg mL(-1)). PMID:25820179

  8. Antifungal Effect of Essential Oils against Fusarium Keratitis Isolates.

    PubMed

    Homa, Mónika; Fekete, Ildikó Pálma; Böszörményi, Andrea; Singh, Yendrembam Randhir Babu; Selvam, Kanesan Panneer; Shobana, Coimbatore Subramanian; Manikandan, Palanisamy; Kredics, László; Vágvölgyi, Csaba; Galgóczy, László

    2015-09-01

    The present study was carried out to investigate the antifungal effects of Cinnamomum zeylanicum, Citrus limon, Juniperus communis, Eucalyptus citriodora, Gaultheria procumbens, Melaleuca alternifolia, Origanum majorana, Salvia sclarea, and Thymus vulgaris essential oils against Fusarium species, the most common etiologic agents of filamentous fungal keratitis in South India. C. zeylanicum essential oil showed strong anti-Fusarium activity, whereas all the other tested essential oils proved to be less effective. The main component of C. zeylanicum essential oil, trans-cinnamaldehyde, was also tested and showed a similar effect as the oil. The in vitro interaction between trans-cinnamaldehyde and natamycin, the first-line therapeutic agent of Fusarium keratitis, was also investigated; an enhanced fungal growth inhibition was observed when these agents were applied in combination. Light and fluorescent microscopic observations revealed that C. zeylanicum essential oil/trans-cinnamaldehyde reduces the cellular metabolism and inhibits the conidia germination. Furthermore, necrotic events were significantly more frequent in the presence of these two compounds. According to our results, C. zeylanicum essential oil/trans-cinnamaldehyde provides a promising basis to develop a novel strategy for the treatment of Fusarium keratitis. PMID:26227503

  9. Antifungal, phytotoxic and toxic metabolites produced by Penicillium purpurogenum.

    PubMed

    Li, He; Wei, Jing; Pan, Shi-Yin; Gao, Jin-Ming; Tian, Jun-Mian

    2014-01-01

    Nine known metabolites, 6,8,1'-tri-O-methyl averantin (1), 6,8-di-O-methyl averufnin (2), 6,8-di-O-methyl averufanin (3), aversin (4), 1,3-dihydroxy-6,8-dimethoxy-9,10-anthraquinone (5), 6,8-di-O-methylnidurufin (6), 6,8-di-O-methyl versiconol (7), 5-methyoxysterigmatocystin (8) and (S)-ornidazole (9), were isolated from the extracts of Penicillium purpurogenum, and their structures were elucidated by using spectroscopic methods. The brine shrimp toxicity, anti-phytopathogenic and phytotoxic effects of these compounds were evaluated. Among them, compounds 1 and 8 exhibited the strongest toxicity against brine shrimp (Artemia salina), with lethality rates of 100% at a low concentration of 10 μM, comparable to the positive control toosendanin. Compounds 1, 4 and 7 moderately inhibited the growth of Botrytis cinerea. Moreover, 4 displayed moderate antifungal effects on Gibberella saubinettii. In addition, compounds 6, 7 and 9 produced the phytotoxic effects on radish seedlings at 100 μM. This is the first report on the isolation of these metabolites from this organism. PMID:25103412

  10. Antifungal Effect of Essential Oils against Fusarium Keratitis Isolates.

    PubMed

    Homa, Mónika; Fekete, Ildikó Pálma; Böszörményi, Andrea; Singh, Yendrembam Randhir Babu; Selvam, Kanesan Panneer; Shobana, Coimbatore Subramanian; Manikandan, Palanisamy; Kredics, László; Vágvölgyi, Csaba; Galgóczy, László

    2015-09-01

    The present study was carried out to investigate the antifungal effects of Cinnamomum zeylanicum, Citrus limon, Juniperus communis, Eucalyptus citriodora, Gaultheria procumbens, Melaleuca alternifolia, Origanum majorana, Salvia sclarea, and Thymus vulgaris essential oils against Fusarium species, the most common etiologic agents of filamentous fungal keratitis in South India. C. zeylanicum essential oil showed strong anti-Fusarium activity, whereas all the other tested essential oils proved to be less effective. The main component of C. zeylanicum essential oil, trans-cinnamaldehyde, was also tested and showed a similar effect as the oil. The in vitro interaction between trans-cinnamaldehyde and natamycin, the first-line therapeutic agent of Fusarium keratitis, was also investigated; an enhanced fungal growth inhibition was observed when these agents were applied in combination. Light and fluorescent microscopic observations revealed that C. zeylanicum essential oil/trans-cinnamaldehyde reduces the cellular metabolism and inhibits the conidia germination. Furthermore, necrotic events were significantly more frequent in the presence of these two compounds. According to our results, C. zeylanicum essential oil/trans-cinnamaldehyde provides a promising basis to develop a novel strategy for the treatment of Fusarium keratitis.

  11. Nest sanitation through defecation: antifungal properties of wood cockroach feces

    NASA Astrophysics Data System (ADS)

    Rosengaus, Rebeca B.; Mead, Kerry; Du Comb, William S.; Benson, Ryan W.; Godoy, Veronica G.

    2013-11-01

    The wood cockroach Cryptocercus punctulatus nests as family units inside decayed wood, a substrate known for its high microbial load. We tested the hypothesis that defecation within their nests, a common occurrence in this species, reduces the probability of fungal development. Conidia of the entomopathogenic fungus, Metarhizium anisopliae, were incubated with crushed feces and subsequently plated on potato dextrose agar. Relative to controls, the viability of fungal conidia was significantly reduced following incubation with feces and was negatively correlated with incubation time. Although the cockroach's hindgut contained abundant β-1,3-glucanase activity, its feces had no detectable enzymatic function. Hence, these enzymes are unlikely the source of the fungistasis. Instead, the antifungal compound(s) of the feces involved heat-sensitive factor(s) of potential microbial origin. When feces were boiled or when they were subjected to ultraviolet radiation and subsequently incubated with conidia, viability was "rescued" and germination rates were similar to those of controls. Filtration experiments indicate that the fungistatic activity of feces results from chemical interference. Because Cryptocercidae cockroaches have been considered appropriate models to make inferences about the factors fostering the evolution of termite sociality, we suggest that nesting in microbe-rich environments likely selected for the coupling of intranest defecation and feces fungistasis in the common ancestor of wood cockroaches and termites. This might in turn have served as a preadaptation that prevented mycosis as these phylogenetically related taxa diverged and evolved respectively into subsocial and eusocial organizations.

  12. Azospirillum brasilense siderophores with antifungal activity against Colletotrichum acutatum.

    PubMed

    Tortora, María L; Díaz-Ricci, Juan C; Pedraza, Raúl O

    2011-04-01

    Anthracnose, caused by the fungus Colletotrichum acutatum is one of the most important diseases in strawberry crop. Due to environmental pollution and resistance produced by chemical fungicides, nowadays biological control is considered a good alternative for crop protection. Among biocontrol agents, there are plant growth-promoting bacteria, such as members of the genus Azospirillum. In this work, we demonstrate that under iron limiting conditions different strains of A. brasilense produce siderophores, exhibiting different yields and rates of production according to their origin. Chemical assays revealed that strains REC2 and REC3 secrete catechol type siderophores, including salicylic acid, detected by thin layer chromatography coupled with fluorescence spectroscopy and gas chromatography-mass spectrometry analysis. Siderophores produced by them showed in vitro antifungal activity against C. acutatum M11. Furthermore, this latter coincided with results obtained from phytopathological tests performed in planta, where a reduction of anthracnose symptoms on strawberry plants previously inoculated with A. brasilense was observed. These outcomes suggest that some strains of A. brasilense could act as biocontrol agent preventing anthracnose disease in strawberry.

  13. Potential of agricultural fungicides for antifungal drug discovery.

    PubMed

    Jampilek, Josef

    2016-01-01

    While it is true that only a small fraction of fungal species are responsible for human mycoses, the increasing prevalence of fungal diseases has highlighted an urgent need to develop new antifungal drugs, especially for systemic administration. This contribution focuses on the similarities between agricultural fungicides and drugs. Inorganic, organometallic and organic compounds can be found amongst agricultural fungicides. Furthermore, fungicides are designed and developed in a similar fashion to drugs based on similar rules and guidelines, with fungicides also having to meet similar criteria of lead-likeness and/or drug-likeness. Modern approved specific-target fungicides are well-characterized entities with a proposed structure-activity relationships hypothesis and a defined mode of action. Extensive toxicological evaluation, including mammalian toxicology assays, is performed during the whole discovery and development process. Thus modern agrochemical research (design of modern agrochemicals) comes close to drug design, discovery and development. Therefore, modern specific-target fungicides represent excellent lead-like structures/models for novel drug design and development.

  14. Azospirillum brasilense siderophores with antifungal activity against Colletotrichum acutatum.

    PubMed

    Tortora, María L; Díaz-Ricci, Juan C; Pedraza, Raúl O

    2011-04-01

    Anthracnose, caused by the fungus Colletotrichum acutatum is one of the most important diseases in strawberry crop. Due to environmental pollution and resistance produced by chemical fungicides, nowadays biological control is considered a good alternative for crop protection. Among biocontrol agents, there are plant growth-promoting bacteria, such as members of the genus Azospirillum. In this work, we demonstrate that under iron limiting conditions different strains of A. brasilense produce siderophores, exhibiting different yields and rates of production according to their origin. Chemical assays revealed that strains REC2 and REC3 secrete catechol type siderophores, including salicylic acid, detected by thin layer chromatography coupled with fluorescence spectroscopy and gas chromatography-mass spectrometry analysis. Siderophores produced by them showed in vitro antifungal activity against C. acutatum M11. Furthermore, this latter coincided with results obtained from phytopathological tests performed in planta, where a reduction of anthracnose symptoms on strawberry plants previously inoculated with A. brasilense was observed. These outcomes suggest that some strains of A. brasilense could act as biocontrol agent preventing anthracnose disease in strawberry. PMID:21234749

  15. Nest sanitation through defecation: antifungal properties of wood cockroach feces.

    PubMed

    Rosengaus, Rebeca B; Mead, Kerry; Du Comb, William S; Benson, Ryan W; Godoy, Veronica G

    2013-11-01

    The wood cockroach Cryptocercus punctulatus nests as family units inside decayed wood, a substrate known for its high microbial load. We tested the hypothesis that defecation within their nests, a common occurrence in this species, reduces the probability of fungal development. Conidia of the entomopathogenic fungus, Metarhizium anisopliae, were incubated with crushed feces and subsequently plated on potato dextrose agar. Relative to controls, the viability of fungal conidia was significantly reduced following incubation with feces and was negatively correlated with incubation time. Although the cockroach's hindgut contained abundant β-1,3-glucanase activity, its feces had no detectable enzymatic function. Hence, these enzymes are unlikely the source of the fungistasis. Instead, the antifungal compound(s) of the feces involved heat-sensitive factor(s) of potential microbial origin. When feces were boiled or when they were subjected to ultraviolet radiation and subsequently incubated with conidia, viability was "rescued" and germination rates were similar to those of controls. Filtration experiments indicate that the fungistatic activity of feces results from chemical interference. Because Cryptocercidae cockroaches have been considered appropriate models to make inferences about the factors fostering the evolution of termite sociality, we suggest that nesting in microbe-rich environments likely selected for the coupling of intranest defecation and feces fungistasis in the common ancestor of wood cockroaches and termites. This might in turn have served as a preadaptation that prevented mycosis as these phylogenetically related taxa diverged and evolved respectively into subsocial and eusocial organizations. PMID:24271031

  16. Antifungal and antibacterial activities of Taxus wallichiana Zucc.

    PubMed

    Nisar, Muhammad; Khan, Inamullah; Ahmad, Bashir; Ali, Ihsan; Ahmad, Waqar; Choudhary, Muhammad Iqbal

    2008-04-01

    Current study was undertaken to evaluate the in vitro antifungal and antibacterial potential of methanol extract and subsequent fractions obtained after partitioning in organic solvents with variable polarity of the aerial parts of the tree Taxus wallichiana Zucc. Traditionally, this plant is often used in folk medicines in Pakistan for treating microbial infections. In order to rationalize the traditional use, methanol extracts of leaf, bark, and heartwood of Taxus wallichiana Zucc. were tested against six bacteria and six fungal strains using the Hole diffusion and macro-dilution methods. All extracts and fractions displayed significant antimicrobial effect. Only three fungal strains, Trichophyton longifusus, Microspoum canis, and Fusarium solani were susceptible to the extracts and fractions with MICs ranging from 0.08 to 200 mg/mL. In case of bacterial strains, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi were susceptible to the extracts and fractions with MICs ranging from 0.08 to 200 mg/mL. Comparison results were carried out using imipinem, miconazole and amphotericin B as standard antibiotics. PMID:18343912

  17. Antifungal and antibacterial activities of Petroselinum crispum essential oil.

    PubMed

    Linde, G A; Gazim, Z C; Cardoso, B K; Jorge, L F; Tešević, V; Glamoćlija, J; Soković, M; Colauto, N B

    2016-01-01

    Parsley [Petroselinum crispum (Mill.) Fuss] is regarded as an aromatic, culinary, and medicinal plant and is used in the cosmetic, food, and pharmaceutical industries. However, few studies with conflicting results have been conducted on the antimicrobial activity of parsley essential oil. In addition, there have been no reports of essential oil obtained from parsley aerial parts, except seeds, as an alternative natural antimicrobial agent. Also, microorganism resistance is still a challenge for health and food production. Based on the demand for natural products to control microorganisms, and the re-evaluation of potential medicinal plants for controlling diseases, the objective of this study was to determine the chemical composition and antibacterial and antifungal activities of parsley essential oil against foodborne diseases and opportunistic pathogens. Seven bacteria and eight fungi were tested. The essential oil major compounds were apiol, myristicin, and b-phellandrene. Parsley essential oil had bacteriostatic activity against all tested bacteria, mainly Staphylococcus aureus, Listeria monocytogenes, and Salmonella enterica, at similar or lower concentrations than at least one of the controls, and bactericidal activity against all tested bacteria, mainly S. aureus, at similar or lower concentrations than at least one of the controls. This essential oil also had fungistatic activity against all tested fungi, mainly, Penicillium ochrochloron and Trichoderma viride, at lower concentrations than the ketoconazole control and fungicidal activity against all tested fungi at higher concentrations than the controls. Parsley is used in cooking and medicine, and its essential oil is an effective antimicrobial agent. PMID:27525894

  18. Antifungal activity of redox-active benzaldehydes that target cellular antioxidation

    PubMed Central

    2011-01-01

    Background Disruption of cellular antioxidation systems should be an effective method for control of fungal pathogens. Such disruption can be achieved with redox-active compounds. Natural phenolic compounds can serve as potent redox cyclers that inhibit microbial growth through destabilization of cellular redox homeostasis and/or antioxidation systems. The aim of this study was to identify benzaldehydes that disrupt the fungal antioxidation system. These compounds could then function as chemosensitizing agents in concert with conventional drugs or fungicides to improve antifungal efficacy. Methods Benzaldehydes were tested as natural antifungal agents against strains of Aspergillus fumigatus, A. flavus, A. terreus and Penicillium expansum, fungi that are causative agents of human invasive aspergillosis and/or are mycotoxigenic. The yeast Saccharomyces cerevisiae was also used as a model system for identifying gene targets of benzaldehydes. The efficacy of screened compounds as effective chemosensitizers or as antifungal agents in formulations was tested with methods outlined by the Clinical Laboratory Standards Institute (CLSI). Results Several benzaldehydes are identified having potent antifungal activity. Structure-activity analysis reveals that antifungal activity increases by the presence of an ortho-hydroxyl group in the aromatic ring. Use of deletion mutants in the oxidative stress-response pathway of S. cerevisiae (sod1Δ, sod2Δ, glr1Δ) and two mitogen-activated protein kinase (MAPK) mutants of A. fumigatus (sakAΔ, mpkCΔ), indicates antifungal activity of the benzaldehydes is through disruption of cellular antioxidation. Certain benzaldehydes, in combination with phenylpyrroles, overcome tolerance of A. fumigatus MAPK mutants to this agent and/or increase sensitivity of fungal pathogens to mitochondrial respiration inhibitory agents. Synergistic chemosensitization greatly lowers minimum inhibitory (MIC) or fungicidal (MFC) concentrations. Effective

  19. An antifungal compound involved in symbiotic germination of Cypripedium macranthos var. rebunense (Orchidaceae).

    PubMed

    Shimura, Hanako; Matsuura, Mayumi; Takada, Noboru; Koda, Yasunori

    2007-05-01

    Germination of orchid seeds fully depends on a symbiotic association with soil-borne fungi, usually Rhizoctonia spp. In contrast to the peaceful symbiotic associations between many other terrestrial plants and mycorrhizal fungi, this association is a life-and-death struggle. The fungi always try to invade the cytoplasm of orchid cells to obtain nutritional compounds. On the other hand, the orchid cells restrict the growth of the infecting hyphae and obtain nutrition by digesting them. It is likely that antifungal compounds are involved in the restriction of fungal growth. Two antifungal compounds, lusianthrin and chrysin, were isolated from the seedlings of Cypripedium macranthos var. rebunense that had developed shoots. The former had a slightly stronger antifungal activity than the latter, and the antifungal spectra of these compounds were relatively specific to the nonpathogenic Rhizoctonia spp. The level of lusianthrin, which was very low in aseptic protocorm-like bodies, dramatically increased following infection with the symbiotic fungus. In contrast, chrysin was not detected in infected protocorm-like bodies. These results suggest that orchid plants equip multiple antifungal compounds and use them at specific developmental stages; lusianthrin maintains the perilous symbiotic association for germination and chrysin helps to protect adult plants. PMID:17445846

  20. Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

    PubMed Central

    Lakshminarayanan, Rajamani; Sridhar, Radhakrishnan; Loh, Xian Jun; Nandhakumar, Muruganantham; Barathi, Veluchamy Amutha; Kalaipriya, Madhaiyan; Kwan, Jia Lin; Liu, Shou Ping; Beuerman, Roger Wilmer; Ramakrishna, Seeram

    2014-01-01

    Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole) electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes. The polyene-loaded fiber mats were noncytotoxic to primary human corneal and sclera fibroblasts. The reduction of toxicity with complete retention of activity of the polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the management of superficial skin infections. PMID:24920895

  1. Antifungal susceptibility of 175 Aspergillus isolates from various clinical and environmental sources.

    PubMed

    Sabino, Raquel; Carolino, Elisabete; Veríssimo, Cristina; Martinez, Marife; Clemons, Karl V; Stevens, David A

    2016-10-01

    Some environmental Aspergillus spp. isolates have been described as resistant to antifungals, potentially causing an emerging medical problem. In the present work, the antifungal susceptibility profile of 41 clinical and 134 environmental isolates of Aspergillus was determined using the CLSI microdilution method. The aim of this study was to compare environmental and clinical isolates with respect to their susceptibility, and assess the potential implications for therapy of isolates encountered in different environments. To our knowledge, this is the first report comparing antifungal susceptibility profiles of Aspergillus collected from different environmental sources (poultries, swineries, beach sand, and hospital environment). Significant differences were found in the distribution of the different species sections for the different sources. Significant differences were also found in the susceptibility profile of the different Aspergillus sections recovered from the various sources. Clear differences were found between the susceptibility of clinical and environmental isolates for caspofungin, amphotericin B and posaconazole, with clinical isolates showing overall greater susceptibility, except for caspofungin. In comparison to clinical isolates, hospital environmental isolates showed significantly less susceptibility to amphotericin B and posaconazole. These data indicate that species section identity and the site from which the isolate was recovered influence the antifungal susceptibility profile, which may affect initial antifungal choices.

  2. Characterisation of the Candida albicans Phosphopantetheinyl Transferase Ppt2 as a Potential Antifungal Drug Target

    PubMed Central

    Dobb, Katharine S.; Kaye, Sarah J.; Beckmann, Nicola; Thain, John L.; Stateva, Lubomira; Birch, Mike; Oliver, Jason D.

    2015-01-01

    Antifungal drugs acting via new mechanisms of action are urgently needed to combat the increasing numbers of severe fungal infections caused by pathogens such as Candida albicans. The phosphopantetheinyl transferase of Aspergillus fumigatus, encoded by the essential gene pptB, has previously been identified as a potential antifungal target. This study investigated the function of its orthologue in C. albicans, PPT2/C1_09480W by placing one allele under the control of the regulatable MET3 promoter, and deleting the remaining allele. The phenotypes of this conditional null mutant showed that, as in A. fumigatus, the gene PPT2 is essential for growth in C. albicans, thus fulfilling one aspect of an efficient antifungal target. The catalytic activity of Ppt2 as a phosphopantetheinyl transferase and the acyl carrier protein Acp1 as a substrate were demonstrated in a fluorescence transfer assay, using recombinant Ppt2 and Acp1 produced and purified from E.coli. A fluorescence polarisation assay amenable to high-throughput screening was also developed. Therefore we have identified Ppt2 as a broad-spectrum novel antifungal target and developed tools to identify inhibitors as potentially new antifungal compounds. PMID:26606674

  3. Fumigant antifungal activity of Myrtaceae essential oils and constituents from Leptospermum petersonii against three Aspergillus species.

    PubMed

    Kim, Eunae; Park, Il-Kwon

    2012-01-01

    Commercial plant essential oils obtained from 11 Myrtaceae plant species were tested for their fumigant antifungal activity against Aspergillus ochraceus, A. flavus, and A. niger. Essential oils extracted from Leptospermum petersonii at air concentrations of 56 × 10(-3) mg/mL and 28 × 10(-3) mg/mL completely inhibited the growth of the three Aspergillus species. However, at an air concentration of 14 × 10(-3) mg/mL, inhibition rates of L. petersonii essential oils were reduced to 20.2% and 18.8% in the case of A. flavus and A. niger, respectively. The other Myrtaceae essential oils (56 × 10(-3) mg/mL) only weakly inhibited the fungi or had no detectable affect. Gas chromatography-mass spectrometry analysis identified 16 compounds in L. petersonii essential oil. The antifungal activity of the identified compounds was tested individually by using standard or synthesized compounds. Of these, neral and geranial inhibited growth by 100%, at an air concentration of 56 × 10(-3) mg/mL, whereas the activity of citronellol was somewhat lover (80%). The other compounds exhibited only moderate or weak antifungal activity. The antifungal activities of blends of constituents identified in L. petersonii oil indicated that neral and geranial were the major contributors to the fumigant and antifungal activities. PMID:22945026

  4. Antifungal Potential of Extracellular Metabolites Produced by Streptomyces hygroscopicus against Phytopathogenic Fungi

    PubMed Central

    Prapagdee, Benjaphorn; Kuekulvong, Chutima; Mongkolsuk, Skorn

    2008-01-01

    Indigenous actinomycetes isolated from rhizosphere soils were assessed for in vitro antagonism against Colletotrichum gloeosporioides and Sclerotium rolfsii. A potent antagonist against both plant pathogenic fungi, designated SRA14, was selected and identified as Streptomyces hygroscopicus. The strain SRA14 highly produced extracellular chitinase and β-1,3-glucanase during the exponential and late exponential phases, respectively. Culture filtrates collected from the exponential and stationary phases inhibited the growth of both the fungi tested, indicating that growth suppression was due to extracellular antifungal metabolites present in culture filtrates. The percentage of growth inhibition by the stationary culture filtrate was significantly higher than that of exponential culture filtrate. Morphological changes such as hyphal swelling and abnormal shapes were observed in fungi grown on potato dextrose agar that contained the culture filtrates. However, the antifungal activity of exponential culture filtrates against both the experimental fungi was significantly reduced after boiling or treatment with proteinase K. There was no significant decrease in the percentage of fungal growth inhibition by the stationary culture filtrate that was treated as above. These data indicated that the antifungal potential of the exponential culture filtrate was mainly due to the presence of extracellular chitinase enzyme, whereas the antifungal activity of the stationary culture filtrate involved the action of unknown thermostable antifungal compound(s). PMID:18825279

  5. Effectiveness of Natural Antifungal Compounds in Controlling Infection by Grapevine Trunk Disease Pathogens through Pruning Wounds

    PubMed Central

    Cobos, Rebeca; Mateos, Rosa María; Álvarez-Pérez, José Manuel; Olego, Miguel Angel; Sevillano, Silvia; González-García, Sandra; Garzón-Jimeno, Enrique

    2015-01-01

    Grapevine trunk fungal pathogens, such as Diplodia seriata and Phaeomoniella chlamydospora, can infect plants through pruning wounds. They cause grapevine trunk diseases and are involved in grapevine decline. Accordingly, the protection of pruning wounds is crucial for the management of grapevine trunk diseases. The efficacy of different natural antifungals in inhibiting the growth of several fungi causing grapevine trunk diseases was evaluated in vitro. The fungi showing greater in vitro efficacy were tested on autoclaved grape wood assays against D. seriata and P. chlamydospora. Based on results from these assays, chitosan oligosaccharide, vanillin, and garlic extract were selected for further evaluation on pruning wounds inoculated with D. seriata and P. chlamydospora in field trials. A significant decrease in plant mortality was observed after 2 years of growth in the plants treated with the different natural antifungals compared to the mortality rate observed in infected plants that were not treated with antifungals. Also, the infection rate for the inoculated pathogens was significantly reduced in plants treated with the selected natural antifungals. Therefore, natural antifungals represent a promising alternative for disease control and could provide significant economic benefits for the grape-growing industry. PMID:26162882

  6. INJECTABLE IN SITU CROSS-LINKING HYDROGELS FOR LOCAL ANTIFUNGAL THERAPY

    PubMed Central

    Hudson, Sarah; Langer, Robert; Fink, Gerald R.; Kohane, Daniel S.

    2009-01-01

    Invasive fungal infections can be devastating, particularly in immunocompromised patients, and difficult to treat with systemic drugs. Furthermore, systemic administration of those medications can have severe side effects. We have developed an injectable local antifungal treatment for direct administration into existing or potential sites of fungal infection. Amphotericin B (AmB), a hydrophobic, potent, and broad-spectrum antifungal agent, was rendered water-soluble by conjugation to a dextran-aldehyde polymer. The dextran-aldehyde-AmB conjugate retained antifungal efficacy against C. albicans. Mixing carboxymethylcellulose-hydrazide with dextran-aldehyde formed a gel that cross-linked in situ by formation of hydrazone bonds. The gel provided in vitro release of antifungal activity for 11 days, and contact with the gel killed Candida for three weeks. There was no apparent tissue toxicity in the murine peritoneum and the gel caused no adhesions. Gels produced by entrapment of a suspension of AmB in CMC-dextran without conjugation of drug to polymers did not release fungicidal activity, but did kill on contact. Injectable systems of these types, containing soluble or insoluble drug formulations, could be useful for treatment of local antifungal infections, with or without concurrent systemic therapy. PMID:19942285

  7. A novel and exploitable antifungal peptide from kale (Brassica alboglabra) seeds.

    PubMed

    Lin, Peng; Ng, Tzi Bun

    2008-10-01

    The aim of this study was to purify and characterize antifungal peptides from kale seeds in view of the paucity of information on antifungal peptides from the family Brassicaceae, and to compare its characteristics with those of published Brassica antifungal peptides. A 5907-Da antifungal peptide was isolated from kale seeds. The isolation procedure comprised affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose and Mono S, and gel filtration on Superdex Peptide. The peptide was adsorbed on the first three chromatographic media. It inhibited mycelial growth in a number of fungal species including Fusarium oxysporum, Helminthosporium maydis, Mycosphaerella arachidicola and Valsa mali, with an IC(50) of 4.3microM, 2.1microM, 2.4microM, and 0.15microM, respectively and exhibited pronounced thermostability and pH stability. It inhibited proliferation of hepatoma (HepG2) and breast cancer (MCF7) cells with an IC(50) of 2.7microM and 3.4microM, and the activity of HIV-1 reverse transcriptase with an IC(50) of 4.9microM. Its N-terminal sequence differed from those of antifungal proteins which have been reported to date.

  8. Antifungal Susceptibility Testing with Etest for Candida Species Isolated from Patients with Oral Candidiasis

    PubMed Central

    Song, You Bum; Ha, Gyoung Yim; Kim, Heesoo

    2015-01-01

    Background The necessity of performing antifungal susceptibility tests is recently increasing because of frequent cases of oral candidiasis caused by antifungal-resistant Candida species. The Etest (BioMerieux, Marcy l'Etoile, France) is a rapid and easy-to-perform in vitro antifungal susceptibility test. Objective The purpose of this study was to determine the minimal inhibitory concentrations (MICs) of antifungal agents by using the Etest for Candida species isolated from patients with oral candidiasis. Methods Forty-seven clinical isolates of Candida species (39 isolates of Candida albicans, 5 isolates of C. glabrata, and 3 isolates of C. tropicalis) were tested along with a reference strain (C. albicans ATCC 90028). The MIC end points of the Etest for fluconazole, itraconazole, voriconazole, and amphotericin B susceptibility were read after the 24-hour incubation of each isolate on RPMI 1640 agar. Results All Candida isolates were found susceptible to voriconazole and amphotericin B. However, all five isolates of C. glabrata were resistant to itraconazole, among which two isolates were also resistant to fluconazole. Conclusion This study revealed that the Etest represented a simple and efficacious method for antifungal susceptibility testing of Candida species isolated from oral candidiasis patients. Therefore, voriconazole and amphotericin B should be recommended as effective alternatives for the treatment of oral candidiasis. PMID:26719641

  9. Purification and modes of antifungal action by Vicia faba cv. Egypt trypsin inhibitor.

    PubMed

    Fang, Evandro Fei; Hassanien, Abdallah Abd Elazeem; Wong, Jack Ho; Bah, Clara Shui Fern; Soliman, Saeed Saad; Ng, Tzi Bun

    2010-10-13

    A new 15 kDa Bowman-Birk type trypsin inhibitor (termed VFTI-E1) from fava beans (Vicia faba cv. Egypt 1) was isolated using liquid chromatography. Though it exhibited substantial homology in N-terminal amino acid sequence to other protease inhibitors, VFTI-E1 showed antiproteolytic activity against trypsin (K(i) 11.9 × 10(-9) M) but hardly any activity against chymotrypsin. It demonstrated antifungal activity toward the filamentous fungus Valsa mali with an IC(50) of 20 μM. The mechanism of its antifungal action toward V. mali included (1) induction of alteration of hyphal morphology, (2) growth inhibition by chitin deposition at hyphal tips, and (3) permeabilization of fungal membrane. The antifungal activity of VFTI-E1 was dependent on the ambient ionic strength as increasing concentrations of NaCl, CaCl(2), and MgCl(2) diminished the activity. The membranolytic action of VFTI-E1 was confined to fungus, but not exerted on human and rabbit erythrocytes. This study sheds light on the mode of hyphal growth inhibitory activity of protease inhibitors with antifungal activity. The antifungal activity of VFTI-E1 amplifies the scope of its potential applications. PMID:20836498

  10. An antifungal compound involved in symbiotic germination of Cypripedium macranthos var. rebunense (Orchidaceae).

    PubMed

    Shimura, Hanako; Matsuura, Mayumi; Takada, Noboru; Koda, Yasunori

    2007-05-01

    Germination of orchid seeds fully depends on a symbiotic association with soil-borne fungi, usually Rhizoctonia spp. In contrast to the peaceful symbiotic associations between many other terrestrial plants and mycorrhizal fungi, this association is a life-and-death struggle. The fungi always try to invade the cytoplasm of orchid cells to obtain nutritional compounds. On the other hand, the orchid cells restrict the growth of the infecting hyphae and obtain nutrition by digesting them. It is likely that antifungal compounds are involved in the restriction of fungal growth. Two antifungal compounds, lusianthrin and chrysin, were isolated from the seedlings of Cypripedium macranthos var. rebunense that had developed shoots. The former had a slightly stronger antifungal activity than the latter, and the antifungal spectra of these compounds were relatively specific to the nonpathogenic Rhizoctonia spp. The level of lusianthrin, which was very low in aseptic protocorm-like bodies, dramatically increased following infection with the symbiotic fungus. In contrast, chrysin was not detected in infected protocorm-like bodies. These results suggest that orchid plants equip multiple antifungal compounds and use them at specific developmental stages; lusianthrin maintains the perilous symbiotic association for germination and chrysin helps to protect adult plants.

  11. In vitro antifungal activity of three geophytic plant extracts against three post-harvest pathogenic fungi.

    PubMed

    Maswada, Hanafey F; Abdallah, Sabry A

    2013-12-01

    Plant extracts appear to be one of the most effective alternative methods of plant diseases control which are less harmful to human beings and environment. In vitro antifungal activity of methanolic extracts of three promising wild geophytic plants against three post-harvest pathogenic fungi using radial growth technique was conducted. These extracts included the shoot system (S) and underground parts (R) of Asparagus stipularis, Cyperus capitatus and Stipagrostis lanata. The tested fungi were Alternaria solani, Aspergillus niger and Rhizopus stolonifer. The results exhibited that, all plant extracts had antifungal activity against the tested fungi. The antifungal activity greatly varied depending on plant parts and/or plant species. R. stolonifer was the most susceptible fungus to the tested plant extracts followed by A. niger and then A. solani. On the other hand, the most effective plant extracts against tested fungi were S. lanata (S) and A. stipularis (R). The most effective plant extracts against R. stolonifer were S. lanata (R) and C. capitatus (S). While, the extracts of A. stipularis (R) and S. lanata (S) were the most effective against A. niger. The extracts of C. capitatus (S) and S. lanata (S) exhibited the highest antifungal activity against A. solani. The results demonstrated that, the methanolic extracts of A. stipularis, C. capitatus and S. lanata had potential antifungal activity against A. solani, A. niger and R. stolonifer. PMID:24506036

  12. Antifungal property of hibicuslide C and its membrane-active mechanism in Candida albicans.

    PubMed

    Hwang, Ji Hong; Jin, Qinglong; Woo, Eun-Rhan; Lee, Dong Gun

    2013-10-01

    In this study, the antifungal activity and mode of action(s) of hibicuslide C derived from Abutilon theophrasti were investigated. Antifungal susceptibility testing showed that hibicuslide C possessed potent activities toward various fungal strains and less hemolytic activity than amphotericin B. To understand the antifungal mechanism(s) of hibicuslide C in Candida albicans, flow cytometric analysis with propidium iodide was done. The results showed that hibicuslide C perturbed the plasma membrane of the C. albicans. The analysis of the transmembrane electrical potential with 3,3'-dipropylthiacarbocyanine iodide [DiSC3(5)] indicated that hibicuslide C induced membrane depolarization. Furthermore, model membrane studies were performed with calcein encapsulating large unilamellar vesicles (LUVs) and FITC-dextran (FD) loaded LUVs. These results demonstrated that the antifungal effects of hibicuslide C on the fungal plasma membrane were through the formation of pores with radii between 2.3 nm and 3.3 nm. Finally, in three dimensional flow cytometric contour plots, a reduced cell sizes by the pore-forming action of hibicuslide C were observed. Therefore, the present study suggests that hibicuslide C exerts its antifungal effect by membrane-active mechanism.

  13. Gene Expression Response of Trichophyton rubrum during Coculture on Keratinocytes Exposed to Antifungal Agents

    PubMed Central

    Komoto, Tatiana Takahasi; Bitencourt, Tamires Aparecida; Silva, Gabriel; Beleboni, Rene Oliveira; Marins, Mozart; Fachin, Ana Lúcia

    2015-01-01

    Trichophyton rubrum is the most common causative agent of dermatomycoses worldwide, causing infection in the stratum corneum, nails, and hair. Despite the high prevalence of these infections, little is known about the molecular mechanisms involved in the fungal-host interaction, particularly during antifungal treatment. The aim of this work was to evaluate the gene expression of T. rubrum cocultured with keratinocytes and treated with the flavonoid trans-chalcone and the glycoalkaloid α-solanine. Both substances showed a marked antifungal activity against T. rubrum strain CBS (MIC = 1.15 and 17.8 µg/mL, resp.). Cytotoxicity assay against HaCaT cells produced IC50 values of 44.18 to trans-chalcone and 61.60 µM to α-solanine. The interaction of keratinocytes with T. rubrum conidia upregulated the expression of genes involved in the glyoxylate cycle, ergosterol synthesis, and genes encoding proteases but downregulated the ABC transporter TruMDR2 gene. However, both antifungals downregulated the ERG1 and ERG11, metalloprotease 4, serine proteinase, and TruMDR2 genes. Furthermore, the trans-chalcone downregulated the genes involved in the glyoxylate pathway, isocitrate lyase, and citrate synthase. Considering the urgent need for more efficient and safer antifungals, these results contribute to a better understanding of fungal-host interactions and to the discovery of new antifungal targets. PMID:26257814

  14. Antifungal characteristics of a fluorescent Pseudomonas strain involved in the biological control of Rhizoctonia solani.

    PubMed

    Pal, K K; Tilak, K V; Saxena, A K; Dey, R; Singh, C S

    2000-09-01

    A plant growth-promoting isolate of a fluorescent Pseudomonas spp. EM85 was found strongly antagonistic to Rhizoctonia solani, a causal agent of damping-off of cotton. The isolate produced HCN (HCN+), siderophore (Sid+), fluorescent pigments (Flu+) and antifungal antibiotics (Afa+). Tn5::lacZ mutagenesis of isolate EM85 resulted in the production of a series of mutants with altered production of HCN, siderophore, fluorescent pigments and antifungal antibiotics. Characterisation of these mutants revealed that the fluorescent pigment produced in PDA and the siderophore produced in CAS agar were not the same. Afa- and Flu- mutants had a smaller inhibition zone when grown with Rhizoctonia solani than the EM85 wild type. Sid- and HCN mutants failed to inhibit the pathogen in vitro. In a pot experiment, mutants deficient in HCN and siderophore production could suppress the damping-off disease by 52%. However, mutants deficient in fluorescent pigments and antifungal antibiotics failed to reduce the disease severity. Treatments with mutants that produced enhanced amounts of fluorescent pigments and antibiotics compared with EM85 wild type, exhibited an increase in biocontrol efficiency. Monitoring of the mutants in the rhizosphere using the lacZ marker showed identical proliferation of mutants and wild type. Purified antifungal compounds (fluorescent pigment and antibiotic) also inhibited the fungus appreciably in a TLC bioassay. Thus, the results indicate that fluorescent pigment and antifungal antibiotic of the fluorescent Pseudomonas spp. EM85 might be involved in the biological suppression of Rhizoctonia-induced damping-off of cotton.

  15. Quantitative Microplate-Based Growth Assay for Determination of Antifungal Susceptibility of Histoplasma capsulatum Yeasts

    PubMed Central

    Goughenour, Kristie D.; Balada-Llasat, Joan-Miquel

    2015-01-01

    Standardized methodologies for determining the antifungal susceptibility of fungal pathogens is central to the clinical management of invasive fungal disease. Yeast-form fungi can be tested using broth macrodilution and microdilution assays. Reference procedures exist for Candida species and Cryptococcus yeasts; however, no standardized methods have been developed for testing the antifungal susceptibility of yeast forms of the dimorphic systemic fungal pathogens. For the dimorphic fungal pathogen Histoplasma capsulatum, susceptibility to echinocandins differs for the yeast and the filamentous forms, which highlights the need to employ Histoplasma yeasts, not hyphae, in antifungal susceptibility tests. To address this, we developed and optimized methodology for the 96-well microtiter plate-based measurement of Histoplasma yeast growth in vitro. Using optical density, the assay is quantitative for fungal growth with a dynamic range greater than 30-fold. Concentration and assay reaction time parameters were also optimized for colorimetric (MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] reduction) and fluorescent (resazurin reduction) indicators of fungal vitality. We employed this microtiter-based assay to determine the antifungal susceptibility patterns of multiple clinical isolates of Histoplasma representing different phylogenetic groups. This methodology fulfills a critical need for the ability to monitor the effectiveness of antifungals on Histoplasma yeasts, the morphological form present in mammalian hosts and, thus, the form most relevant to disease. PMID:26246483

  16. Synergy Between Polyvinylpyrrolidone-Coated Silver Nanoparticles and Azole Antifungal Against Drug-Resistant Candida albicans.

    PubMed

    Sun, Lingmei; Liao, Kai; Li, Yiping; Zhao, Lei; Liang, Sai; Guo, Dan; Hu, Jun; Wang, Dayong

    2016-03-01

    In the clinical practice, resistance of Candida albicans to antifungal agents has frequently emerged. Silver-nanoparticles (Ag-NPs) have been demonstrated to have the antifungal property. We investigated the potential for synergy between polyvinylpyrrolidone (PVP)-coated Ag-NPs and azole antifungal, such as fluconazole or voriconazole, against drug-resistant C. albicans strain CA10. When antifungal agent was examined alone, fluconazole and voriconazole did not kill drug-resistant C. albicans, and PVP-coated Ag-NPs had only the moderate killing ability. In contrast, the combinational treatment of PVP-coated Ag-NPs with fluconazole or voriconazole was effective in being against the drug-resistant C. albicans. After the combinational treatment, we detected the disruption of cell membrane integrity, the tendency of PVP-coated Ag-NPs to adhere to cell membrane, and the inhibition of budding process. Moreover, after the combinational treatment, the defects in ergosterol signaling and efflux pump functions were detected. Our results suggest that the combinational use of engineered nanomaterials (ENMs), such as PVP-coated Ag-NPs, with the conventional antifungal may be a viable strategy to combat drug-resistant fungal infection.

  17. Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

    PubMed Central

    de Araújo, Rodrigo S. A.; Guerra, Felipe Q. S.; de O. Lima, Edeltrudes; de Simone, Carlos A.; Tavares, Josean F.; Scotti, Luciana; Scotti, Marcus T.; de Aquino, Thiago M.; de Moura, Ricardo O.; Mendonça, Francisco J. B.; Barbosa-Filho, José M.

    2013-01-01

    The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 μg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO2 and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity. PMID:23306152

  18. Expression in Escherichia coli, purification, refolding and antifungal activity of an osmotin from Solanum nigrum

    PubMed Central

    Campos, Magnólia de A; Silva, Marilia S; Magalhães, Cláudio P; Ribeiro, Simone G; Sarto, Rafael PD; Vieira, Eduardo A; Grossi de Sá, Maria F

    2008-01-01

    Background Heterologous protein expression in microorganisms may contribute to identify and demonstrate antifungal activity of novel proteins. The Solanum nigrum osmotin-like protein (SnOLP) gene encodes a member of pathogenesis-related (PR) proteins, from the PR-5 sub-group, the last comprising several proteins with different functions, including antifungal activity. Based on deduced amino acid sequence of SnOLP, computer modeling produced a tertiary structure which is indicative of antifungal activity. Results To validate the potential antifungal activity of SnOLP, a hexahistidine-tagged mature SnOLP form was overexpressed in Escherichia coli M15 strain carried out by a pQE30 vector construction. The urea solubilized His6-tagged mature SnOLP protein was affinity-purified by immobilized-metal (Ni2+) affinity column chromatography. As SnOLP requires the correct formation of eight disulfide bonds, not correctly formed in bacterial cells, we adapted an in vitro method to refold the E. coli expressed SnOLP by using reduced:oxidized gluthatione redox buffer. This method generated biologically active conformations of the recombinant mature SnOLP, which exerted antifungal action towards plant pathogenic fungi (Fusarium solani f. sp.glycines, Colletotrichum spp., Macrophomina phaseolina) and oomycete (Phytophthora nicotiana var. parasitica) under in vitro conditions. Conclusion Since SnOLP displays activity against economically important plant pathogenic fungi and oomycete, it represents a novel PR-5 protein with promising utility for biotechnological applications. PMID:18334031

  19. Resistance to antifungal agents in the critical care setting: problems and perspectives.

    PubMed

    Martins, M D; Rex, J H

    1996-08-01

    As is the case with antibacterial agents, the increasing use of antifungal agents has led to development of antifungal resistance, the most clinically important of which is the resistance of Candida to fluconazole. While mutation to high-level fluconazole resistance is possible, the most important aspect of fluconazole resistance for patients in the ICU is the possibility of an epidemiologic shift away from such susceptible species as C. albicans and C. parapsilosis toward the most resistant species, such as C. glabrata and C. krusei. Resistance to amphotericin B by Candida is also possible, but less frequent. Strategies for treating invasive Candida infections must consider the relative rates of non-C. albicans Candida infection and the likelihood of antifungal resistance. The agents that cause invasive mold infections in the ICU are intrinsically moderately resistant to the available antifungal agents, and therapy depends less on the choice of antifungal therapy than on the correction of predisposing factors. The role of susceptibility testing as a guide in selecting appropriate therapy for all of these infections is as yet incompletely defined, but testing for resistance to fluconazole may soon be ready for clinical use. PMID:8856751

  20. Antifungal potential of extracellular metabolites produced by Streptomyces hygroscopicus against phytopathogenic fungi.

    PubMed

    Prapagdee, Benjaphorn; Kuekulvong, Chutima; Mongkolsuk, Skorn

    2008-01-01

    Indigenous actinomycetes isolated from rhizosphere soils were assessed for in vitro antagonism against Colletotrichum gloeosporioides and Sclerotium rolfsii. A potent antagonist against both plant pathogenic fungi, designated SRA14, was selected and identified as Streptomyces hygroscopicus. The strain SRA14 highly produced extracellular chitinase and beta-1,3-glucanase during the exponential and late exponential phases, respectively. Culture filtrates collected from the exponential and stationary phases inhibited the growth of both the fungi tested, indicating that growth suppression was due to extracellular antifungal metabolites present in culture filtrates. The percentage of growth inhibition by the stationary culture filtrate was significantly higher than that of exponential culture filtrate. Morphological changes such as hyphal swelling and abnormal shapes were observed in fungi grown on potato dextrose agar that contained the culture filtrates. However, the antifungal activity of exponential culture filtrates against both the experimental fungi was significantly reduced after boiling or treatment with proteinase K. There was no significant decrease in the percentage of fungal growth inhibition by the stationary culture filtrate that was treated as above. These data indicated that the antifungal potential of the exponential culture filtrate was mainly due to the presence of extracellular chitinase enzyme, whereas the antifungal activity of the stationary culture filtrate involved the action of unknown thermostable antifungal compound(s). PMID:18825279

  1. Isolation, characterization and antifungal activity of major constituents of the Himalayan lichen Parmelia reticulata Tayl.

    PubMed

    Goel, Mayurika; Dureja, Prem; Rani, Archna; Uniyal, Prem L; Laatsch, Hartmut

    2011-03-23

    Antifungal activity of hexane, ethyl acetate and methanol extracts of Parmelia reticulata was evaluated against soilborne pathogenic fungi, namely, Sclerotium rolfsii, Rhizoctonia solani, R. bataticola, Fusarium udum, Pythium aphanidermatum and P. debaryanum by poisoned food technique. Maximum antifungal activity was exhibited by hexane and ethyl acetate extracts against most of the test pathogens. Secondary metabolites, namely, (±)-isousnic acid, (±)-protolichesterinic acid, atranorin, evernyl, ethyl hematommate, ethyl orsellinate, methyl hematommate (3-formyl-2,4-dihydroxy-6-methylbenzoic acid methyl ester), 2-hydroxy-4-methoxy-3,6-dimethylbenzoic acid, 1-hydroxy-3,6-dimethoxy-8-methyl-xanthen-9-one, baeomycesic acid and salazinic acid, were isolated from the above extracts and identified by 1H NMR, 13C NMR and mass spectroscopic methods. When these metabolites were tested for antifungal activity against test pathogens, maximum antifungal activity was exhibited by (±)-protolichesterinic acid against R. solani (ED50=23.09 μg mL(-1)) and P. debaryanum (ED50=16.07 μg mL(-1)) and by atranorin against S. rolfsii (ED50=39.70 μg mL(-1)). The antifungal activity of protolichesterinic acid was found to be comparable to that of hexaconazole, a commercial fungicide. PMID:21351753

  2. Synergy Between Polyvinylpyrrolidone-Coated Silver Nanoparticles and Azole Antifungal Against Drug-Resistant Candida albicans.

    PubMed

    Sun, Lingmei; Liao, Kai; Li, Yiping; Zhao, Lei; Liang, Sai; Guo, Dan; Hu, Jun; Wang, Dayong

    2016-03-01

    In the clinical practice, resistance of Candida albicans to antifungal agents has frequently emerged. Silver-nanoparticles (Ag-NPs) have been demonstrated to have the antifungal property. We investigated the potential for synergy between polyvinylpyrrolidone (PVP)-coated Ag-NPs and azole antifungal, such as fluconazole or voriconazole, against drug-resistant C. albicans strain CA10. When antifungal agent was examined alone, fluconazole and voriconazole did not kill drug-resistant C. albicans, and PVP-coated Ag-NPs had only the moderate killing ability. In contrast, the combinational treatment of PVP-coated Ag-NPs with fluconazole or voriconazole was effective in being against the drug-resistant C. albicans. After the combinational treatment, we detected the disruption of cell membrane integrity, the tendency of PVP-coated Ag-NPs to adhere to cell membrane, and the inhibition of budding process. Moreover, after the combinational treatment, the defects in ergosterol signaling and efflux pump functions were detected. Our results suggest that the combinational use of engineered nanomaterials (ENMs), such as PVP-coated Ag-NPs, with the conventional antifungal may be a viable strategy to combat drug-resistant fungal infection. PMID:27455637

  3. 78 FR 23497 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ... . II. Summary of Petitioned-For Tolerance In the Federal Register of May 23, 2012 (Volume 77, FR 30481... Register of Wednesday, May 11, 2011 (76 FR 27261) (FRL-8873-2). C. Exposure Assessment 1. Dietary exposure... actions from review under Executive Order 12866, entitled ``Regulatory Planning and Review'' (58 FR...

  4. 77 FR 38199 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ....gov/dockets . II. Summary of Petitioned-For Tolerances In the Federal Register of July 20, 2011 (76 FR... Register of Wednesday, May 11, 2011 (76 FR 27261) (FRL-8873-2). C. Exposure Assessment 1. Dietary exposure... Executive Order 12866, entitled ``Regulatory Planning and Review'' (58 FR 51735, October 4, 1993)....

  5. 76 FR 27261 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ... Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 1997). This final rule does not contain any... Address Environmental Justice in Minority Populations and Low-Income Populations (59 FR 7629, February 16... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL...

  6. 77 FR 75039 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    .... Summary of Petitioned-for Tolerance In the Federal Register of November 9, 2011 (Volume 76, FR 69690) (FRL..., 2011 (76 FR 27261) (FRL-8873-2). C. Exposure Assessment 1. Dietary exposure from food and feed uses. In..., entitled ``Regulatory Planning and Review'' (58 FR 51735, October 4, 1993). Because this final rule...

  7. Human neutrophil-mediated nonoxidative antifungal activity against Cryptococcus neoformans.

    PubMed

    Mambula, S S; Simons, E R; Hastey, R; Selsted, M E; Levitz, S M

    2000-11-01

    It has long been appreciated that polymorphonuclear leukocytes (PMN) kill Cryptococcus neoformans, at least in part via generation of fungicidal oxidants. The aim of this study was to examine the contribution of nonoxidative mechanisms to the inhibition and killing of C. neoformans. Treatment of human PMN with inhibitors and scavengers of respiratory burst oxidants only partially reversed anticryptococcal activity, suggesting that both oxidative and nonoxidative mechanisms were operative. To define the mediators of nonoxidative anticryptococcal activity, PMN were fractionated into cytoplasmic, primary (azurophil) granule, and secondary (specific) granule fractions. Incubation of C. neoformans with these fractions for 18 h resulted in percent inhibition of growth of 67.4 +/- 3.4, 84.6 +/- 4.4, and 29.2 +/- 10.5 (mean +/- standard error, n = 3), respectively. Anticryptococcal activity of the cytoplasmic fraction was abrogated by zinc and depletion of calprotectin. Antifungal activity of the primary granules was significantly reduced by pronase treatment, boiling, high ionic strength, and magnesium but not calcium. Fractionation of the primary granules by reverse phase high-pressure liquid chromatography on a C(4) column over an acetonitrile gradient revealed multiple peaks with anticryptococcal activity. Of these, peaks 1 and 6 had substantial fungistatic and fungicidal activity. Peak 1 was identified by acid-urea polyacrylamide gel electrophoresis (PAGE) and mass spectroscopy as human neutrophil proteins (defensins) 1 to 3. Analysis of peak 6 by sodium dodecyl sulfate-PAGE revealed multiple bands. Thus, human PMN have nonoxidative anticryptococcal activity residing principally in their cytoplasmic and primary granule fractions. Calprotectin mediates the cytoplasmic activity, whereas multiple proteins, including defensins, are responsible for activity of the primary granules. PMID:11035733

  8. Antifungal drug resistance evokedvia RNAi-dependent epimutations

    PubMed Central

    Calo, Silvia; Shertz-Wall, Cecelia; Lee, Soo Chan; Bastidas, Robert J.; Nicolás, Francisco E.; Granek, Joshua A.; Mieczkowski, Piotr; Torres-Martinez, Santiago; Ruiz-Vazquez, Rosa M.; Cardenas, Maria E.; Heitman, Joseph

    2014-01-01

    Microorganisms evolve via mechanisms spanning sexual/parasexual reproduction, mutators, aneuploidy, Hsp90, and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show the human fungal pathogen Mucor circinelloides develops spontaneous resistance to the antifungal drug FK506 (tacrolimus) via two distinct mechanisms. One involves Mendelian mutations that confer stable drug resistance; the other occurs via an epigenetic RNA interference (RNAi)-mediated pathway resulting in unstable drug resistance. The peptidyl-prolyl isomerase FKBP12 interacts with FK506 forming a complex that inhibits the protein phosphatase calcineurin1. Calcineurin inhibition by FK506 blocks M. circinelloides transition to hyphae and enforces yeast growth2. Mutations in the fkbA gene encoding FKBP12 or the calcineurin cnbR or cnaA genes confer FK506 resistance (FK506R) and restore hyphal growth. In parallel, RNAi is spontaneously triggered to silence the FKBP12 fkbA gene, giving rise to drug-resistant epimutants. FK506R epimutants readily reverted to the drug-sensitive wild-type (WT) phenotype when grown without drug. The establishment of these epimutants is accompanied by generation of abundant fkbA small RNA (sRNA) and requires the RNAi pathway as well as other factors that constrain or reverse the epimutant state. Silencing involves generation of a double-stranded RNA (dsRNA) trigger intermediate from the fkbA mature mRNA to produce antisense fkbA RNA. This study uncovers a novel epigenetic RNAi-based epimutation mechanism controlling phenotypic plasticity, with possible implications for antimicrobial drug resistance and RNAi-regulatory mechanisms in fungi and other eukaryotes. PMID:25079329

  9. Antifungal activities of origanum oil against Candida albicans.

    PubMed

    Manohar, V; Ingram, C; Gray, J; Talpur, N A; Echard, B W; Bagchi, D; Preuss, H G

    2001-12-01

    The antimicrobial properties of volatile aromatic oils from medicinal as well as other edible plants has been recognized since antiquity. Origanum oil, which is used as a food flavoring agent, possesses a broad spectrum of in vitro antimicrobial activities attributed to the high content of phenolic derivatives such as carvacrol and thymol. In the present study, antifungal properties of origanum oil were examined both in vitro and in vivo. Using Candida albicans in broth cultures and a micro dilution method, comparative efficacy of origanum oil, carvacrol, nystatin and amphotericin B were examined in vitro. Origanum oil at 0.25 mg/ml was found to completely inhibit the growth of C. albicans in culture. Growth inhibitions of 75% and >50% were observed at 0.125 mg/ml and 0.0625 mg/ml level, respectively. In addition, both the germination and the mycelial growth of C. albicans were found to be inhibited by origanum oil and carvacrol in a dose-dependent manner. Furthermore, the therapeutic efficacy of origanum oil was examined in an experimental murine systemic candidiasis model. Groups of mice (n = 6) infected with C. albicans (5 x LD50) were fed varying amounts of origanum oil in a final vol. of 0.1 ml of olive oil (vehicle). The daily administration of 8.6 mg of origanum oil in 100 microl of olive oil/kg body weight for 30 days resulted in 80% survivability, with no renal burden of C. albicans as opposed to the group of mice fed olive oil alone, who died within 10 days. Similar results were obtained with carvacrol. However, mice fed origanum oil exhibited cosmetically better clinical appearance compared to those cured with carvacrol. The results from our study encourage examination of the efficacy of origanum oil in other forms of systemic and superficial fungal infections and exploration of its broad spectrum effect against other pathogenic manifestations including malignancy. PMID:11855736

  10. Evolution of Chemical Diversity in Echinocandin Lipopeptide Antifungal Metabolites.

    PubMed

    Yue, Qun; Chen, Li; Zhang, Xiaoling; Li, Kuan; Sun, Jingzu; Liu, Xingzhong; An, Zhiqiang; Bills, Gerald F

    2015-07-01

    The echinocandins are a class of antifungal drugs that includes caspofungin, micafungin, and anidulafungin. Gene clusters encoding most of the structural complexity of the echinocandins provided a framework for hypotheses about the evolutionary history and chemical logic of echinocandin biosynthesis. Gene orthologs among echinocandin-producing fungi were identified. Pathway genes, including the nonribosomal peptide synthetases (NRPSs), were analyzed phylogenetically to address the hypothesis that these pathways represent descent from a common ancestor. The clusters share cooperative gene contents and linkages among the different strains. Individual pathway genes analyzed in the context of similar genes formed unique echinocandin-exclusive phylogenetic lineages. The echinocandin NRPSs, along with the NRPS from the inp gene cluster in Aspergillus nidulans and its orthologs, comprise a novel lineage among fungal NRPSs. NRPS adenylation domains from different species exhibited a one-to-one correspondence between modules and amino acid specificity that is consistent with models of tandem duplication and subfunctionalization. Pathway gene trees and Ascomycota phylogenies are congruent and consistent with the hypothesis that the echinocandin gene clusters have a common origin. The disjunct Eurotiomycete-Leotiomycete distribution appears to be consistent with a scenario of vertical descent accompanied by incomplete lineage sorting and loss of the clusters from most lineages of the Ascomycota. We present evidence for a single evolutionary origin of the echinocandin family of gene clusters and a progression of structural diversification in two fungal classes that diverged approximately 290 to 390 million years ago. Lineage-specific gene cluster evolution driven by selection of new chemotypes contributed to diversification of the molecular functionalities. PMID:26024901

  11. Biogenic silver nanoparticles: efficient and effective antifungal agents

    NASA Astrophysics Data System (ADS)

    Netala, Vasudeva Reddy; Kotakadi, Venkata Subbaiah; Domdi, Latha; Gaddam, Susmila Aparna; Bobbu, Pushpalatha; Venkata, Sucharitha K.; Ghosh, Sukhendu Bikash; Tartte, Vijaya

    2016-04-01

    Biogenic synthesis of silver nanoparticles (AgNPs) by exploiting various plant materials is an emerging field and considered green nanotechnology as it involves simple, cost effective and ecofriendly procedure. In the present study AgNPs were successfully synthesized using aqueous callus extract of Gymnema sylvestre. The aqueous callus extract treated with 1nM silver nitrate solution resulted in the formation of AgNPs and the surface plasmon resonance (SPR) of the formed AgNPs showed a peak at 437 nm in the UV Visible spectrum. The synthesized AgNPs were characterized using Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM), and X-ray diffraction spectroscopy (XRD). FTIR spectra showed the peaks at 3333, 2928, 2361, 1600, 1357 and 1028 cm-1 which revealed the role of different functional groups possibly involved in the synthesis and stabilization of AgNPs. TEM micrograph clearly revealed the size of the AgNPs to be in the range of 3-30 nm with spherical shape and poly-dispersed nature; it is further confirmed by Particle size analysis that the stability of AgNPs is due its high negative Zeta potential (-36.1 mV). XRD pattern revealed the crystal nature of the AgNPs by showing the braggs peaks corresponding to (111), (200), (220) and (311) planes of face-centered cubic crystal phase of silver. Selected area electron diffraction pattern showed diffraction rings and confirmed the crystalline nature of synthesized AgNPs. The synthesized AgNPs exhibited effective antifungal activity against Candida albicans, Candida nonalbicans and Candida tropicalis.

  12. Laccase Catalyzed Synthesis of Iodinated Phenolic Compounds with Antifungal Activity

    PubMed Central

    Ihssen, Julian; Schubert, Mark; Thöny-Meyer, Linda; Richter, Michael

    2014-01-01

    Iodine is a well known antimicrobial compound. Laccase, an oxidoreductase which couples the one electron oxidation of diverse phenolic and non-phenolic substrates to the reduction of oxygen to water, is capable of oxidizing unreactive iodide to reactive iodine. We have shown previously that laccase-iodide treatment of spruce wood results in a wash-out resistant antimicrobial surface. In this study, we investigated whether phenolic compounds such as vanillin, which resembles sub-structures of softwood lignin, can be directly iodinated by reacting with laccase and iodide, resulting in compounds with antifungal activity. HPLC-MS analysis showed that vanillin was converted to iodovanillin by laccase catalysis at an excess of potassium iodide. No conversion of vanillin occurred in the absence of enzyme. The addition of redox mediators in catalytic concentrations increased the rate of iodide oxidation ten-fold and the yield of iodovanillin by 50%. Iodinated phenolic products were also detected when o-vanillin, ethyl vanillin, acetovanillone and methyl vanillate were incubated with laccase and iodide. At an increased educt concentration of 0.1 M an almost one to one molar ratio of iodide to vanillin could be used without compromising conversion rate, and the insoluble iodovanillin product could be recovered by simple centrifugation. The novel enzymatic synthesis procedure fulfills key criteria of green chemistry. Biocatalytically produced iodovanillin and iodo-ethyl vanillin had significant growth inhibitory effects on several wood degrading fungal species. For Trametes versicolor, a species causing white rot of wood, almost complete growth inhibition and a partial biocidal effect was observed on agar plates. Enzymatic tests indicated that the iodinated compounds acted as enzyme responsive, antimicrobial materials. PMID:24594755

  13. Evolution of Chemical Diversity in Echinocandin Lipopeptide Antifungal Metabolites

    PubMed Central

    Yue, Qun; Chen, Li; Zhang, Xiaoling; Li, Kuan; Sun, Jingzu; Liu, Xingzhong

    2015-01-01

    The echinocandins are a class of antifungal drugs that includes caspofungin, micafungin, and anidulafungin. Gene clusters encoding most of the structural complexity of the echinocandins provided a framework for hypotheses about the evolutionary history and chemical logic of echinocandin biosynthesis. Gene orthologs among echinocandin-producing fungi were identified. Pathway genes, including the nonribosomal peptide synthetases (NRPSs), were analyzed phylogenetically to address the hypothesis that these pathways represent descent from a common ancestor. The clusters share cooperative gene contents and linkages among the different strains. Individual pathway genes analyzed in the context of similar genes formed unique echinocandin-exclusive phylogenetic lineages. The echinocandin NRPSs, along with the NRPS from the inp gene cluster in Aspergillus nidulans and its orthologs, comprise a novel lineage among fungal NRPSs. NRPS adenylation domains from different species exhibited a one-to-one correspondence between modules and amino acid specificity that is consistent with models of tandem duplication and subfunctionalization. Pathway gene trees and Ascomycota phylogenies are congruent and consistent with the hypothesis that the echinocandin gene clusters have a common origin. The disjunct Eurotiomycete-Leotiomycete distribution appears to be consistent with a scenario of vertical descent accompanied by incomplete lineage sorting and loss of the clusters from most lineages of the Ascomycota. We present evidence for a single evolutionary origin of the echinocandin family of gene clusters and a progression of structural diversification in two fungal classes that diverged approximately 290 to 390 million years ago. Lineage-specific gene cluster evolution driven by selection of new chemotypes contributed to diversification of the molecular functionalities. PMID:26024901

  14. Aspergillus nidulans galactofuranose biosynthesis affects antifungal drug sensitivity.

    PubMed

    Alam, Md Kausar; El-Ganiny, Amira M; Afroz, Sharmin; Sanders, David A R; Liu, Juxin; Kaminskyj, Susan G W

    2012-12-01

    The cell wall is essential for fungal survival in natural environments. Many fungal wall carbohydrates are absent from humans, so they are a promising source of antifungal drug targets. Galactofuranose (Galf) is a sugar that decorates certain carbohydrates and lipids. It comprises about 5% of the Aspergillus fumigatus cell wall, and may play a role in systemic aspergillosis. We are studying Aspergillus wall formation in the tractable model system, A. nidulans. Previously we showed single-gene deletions of three sequential A. nidulans Galf biosynthesis proteins each caused similar hyphal morphogenesis defects and 500-fold reduced colony growth and sporulation. Here, we generated ugeA, ugmA and ugtA strains controlled by the alcA(p) or niiA(p) regulatable promoters. For repression and expression, alcA(p)-regulated strains were grown on complete medium with glucose or threonine, whereas niiA(p)-regulated strains were grown on minimal medium with ammonium or nitrate. Expression was assessed by qPCR and colony phenotype. The alcA(p) and niiA(p) strains produced similar effects: colonies resembling wild type for gene expression, and resembling deletion strains for gene repression. Galf immunolocalization using the L10 monoclonal antibody showed that ugmA deletion and repression phenotypes correlated with loss of hyphal wall Galf. None of the gene manipulations affected itraconazole sensitivity, as expected. Deletion of any of ugmA, ugeA, ugtA, their repression by alcA(p) or niiA(p), OR, ugmA overexpression by alcA(p), increased sensitivity to Caspofungin. Strains with alcA(p)-mediated overexpression of ugeA and ugtA had lower caspofungin sensitivity. Galf appears to play an important role in A. nidulans growth and vigor.

  15. Chiral profiling of azole antifungals in municipal wastewater and recipient rivers of the Pearl River Delta, China.

    PubMed

    Huang, Qiuxin; Wang, Zhifang; Wang, Chunwei; Peng, Xianzhi

    2013-12-01

    Enantiomeric compositions and fractions (EFs) of three chiral imidazole (econazole, ketoconazole, and miconazole) and one chiral triazole (tebuconazole) antifungals were investigated in wastewater, river water, and bed sediment of the Pearl River Delta, South China. The imidazole pharmaceuticals in the untreated wastewater were racemic to weakly nonracemic (EFs of 0.450-0.530) and showed weak enantioselectivity during treatment in the sewage treatment plant. The EFs of the dissolved azole antifungals were usually different from those of the sorbed azoles in the suspended particulate matter, suggesting different behaviors for the enantiomers of the chiral azole antifungals in the dissolved and particulate phases of the wastewater. The azole antifungals were widely present in the rivers. The bed sediment was a sink for the imidazole antifungals. The imidazoles were prevalently racemic, whereas tebuconazole was widely nonracemic in the rivers. Seasonal effects were observed on distribution and chirality of the azole antifungals. Concentrations of the azole antifungals in the river water were relatively higher in winter than in spring and summer while the EF of miconazole in the river water was higher in summer. The mechanism of enantiomeric behavior of the chiral azole antifungals in the environment warrants further research.

  16. Components of the Calcium-Calcineurin Signaling Pathway in Fungal Cells and Their Potential as Antifungal Targets

    PubMed Central

    Liu, Shuyuan; Hou, Yinglong; Liu, Weiguo; Lu, Chunyan; Wang, Weixin

    2015-01-01

    In recent years, the emergence of fungal resistance has become frequent, partly due to the widespread clinical use of fluconazole, which is minimally toxic and effective in the prevention and treatment of Candida albicans infections. The limited selection of antifungal drugs for clinical fungal infection therapy has prompted us to search for new antifungal drug targets. Calcium, which acts as the second messenger in both mammals and fungi, plays a direct role in controlling the expression patterns of its signaling systems and has important roles in cell survival. In addition, calcium and some of the components, mainly calcineurin, in the fungal calcium signaling pathway mediate fungal resistance to antifungal drugs. Therefore, an overview of the components of the fungal calcium-calcineurin signaling network and their potential roles as antifungal targets is urgently needed. The calcium-calcineurin signaling pathway consists of various channels, transporters, pumps, and other proteins or enzymes. Many transcriptional profiles have indicated that mutant strains that lack some of these components are sensitized to fluconazole or other antifungal drugs. In addition, many researchers have identified efficient compounds that exhibit antifungal activity by themselves or in combination with antifungal drugs by targeting some of the components in the fungal calcium-calcineurin signaling pathway. This targeting disrupts Ca2+ homeostasis, which suggests that this pathway contains potential targets for the development of new antifungal drugs. PMID:25636321

  17. Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several benzoic acid analogs showed antifungal activity against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis. Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids increased by addition of a methyl, methoxyl...

  18. Facile fabrication of graphene oxide loaded with silver nanoparticles as antifungal materials

    NASA Astrophysics Data System (ADS)

    Cui, Jianghu; Yang, Yunhua; Zheng, Mingtao; Liu, Yingliang; Xiao, Yong; Lei, Bingfu; Chen, Wei

    2014-12-01

    Graphene oxide loaded silver nanoparticles (GO-Ag) were synthesized using a simple method. Our evidence showed that silver nanoparticles (Ag NPs) were successfully loaded on the surface of graphene oxide sheets. The antifungal property of GO-Ag composites was investigated. The results revealed that the obtained GO-Ag composites exhibit enhanced antifungal property in comparison with that of Ag NPs. The toxicity of GO-Ag and Ag NPs were systematically evaluated. The study of cell viability, lactate dehydrogenase, reactive oxygen species, apoptosis/necrosis and hemolysis revealed that GO-Ag composites have lower cytotoxicity and better blood compatibility than Ag NPs. Therefore, these findings provide nanotoxicological information regarding GO-Ag composites which may be alternative antifungal materials in their application of biomedical fields.

  19. A novel antifungal protein with lysozyme-like activity from seeds of Clitoria ternatea.

    PubMed

    K, Ajesh; K, Sreejith

    2014-06-01

    An antifungal protein with a molecular mass of 14.3 kDa was isolated from the seeds of butterfly pea (Clitoria ternatea) and designated as Ct protein. The antifungal protein was purified using different methods including ammonium sulphate precipitation, ion exchange chromatography on DEAE-cellulose and gel filtration on Sephadex G-50 column. Ct protein formed a single colourless rod-shaped crystal by hanging drop method after 7 days of sample loading. The protein showed lytic activity against Micrococcus luteus and broad-spectrum, fungicidal activity, particularly against the most clinically relevant yeasts, such as Cryptococcus neoformans, Cryptococcus albidus, Cryptococcus laurentii, Candida albicans and Candida parapsilosis. It also exerted an inhibitory activity on mycelial growth in several mould species including Curvularia sp., Alternaria sp., Cladosporium sp., Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Rhizopus sp., and Sclerotium sp. The present study adds to the literature on novel seed proteins with antifungal activity. PMID:24691882

  20. Analysis Of Volatile Fingerprints: A Rapid Screening Method For Antifungal Agents For Efficacy Against Dermatophytes

    NASA Astrophysics Data System (ADS)

    Naraghi, Kamran; Sahgal, Natasha; Adriaans, Beverley; Barr, Hugh; Magan, Naresh

    2009-05-01

    The potential of using an electronic nose (E. nose) for rapid screening dermatophytes to antifungal agents was studied. In vitro, the 50 and 90% effective concentration (EC) values of five antifungal agents for T. rubrum and T. mentagrophytes were obtained by mycelial growth assays. Then, the qualitative volatile production patterns of the growth responses of these fungi to these values were incorporated into solid medium were analysed after 96-120 hrs incubation at 25° C using headspace analyses. Overall, results, using PCA and CA demonstrated that it is possible to differentiate between various treatments within 96-120 hrs. This study showed that potential exists for using qualitative volatile patterns as a rapid screening method for antifungal agents for microorganism. This approach could also facilitate the monitoring of antimicrobial drug activities and infection control programmes and perhaps drug resistance build up in microbial species.