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1

COMPARATIVE LIVER P450 ENZYME ACTIVITY AND HISTOPATHOLOGY IN MICE TREATED WITH THE CONAZOLE FUNGICIDES: MYCLOBUTANIL, PROPICONAZOLE AND TRIADIMETON  

EPA Science Inventory

Conazoles used in agriculture and pharmaceutical products comprise a class of chemicals which inhibit ergosterol biosynthesis to act as fungicides. Both propiconazole and triadimefon are hepatotoxic and hepatotumorigenic in mice, while myclobutanil is not a mouse liver tumorigen....

2

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

PubMed

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 present only after 30 days in rats treated with the high dose of triadimefon. A dose-dependent decrease in T4 was present after 4 days with all 3 compounds but only the high doses of propiconazole and triadimefon produced decreased T4 after 30 days. T3 was decreased after high-dose triadimefon after 4 days and in a dose-dependent manner for all compounds after 30 days. Thyroid hormone levels did not differ from control values after 90 days and TSH was not increased in any exposure group. A unique pattern of toxic responses was not identified for each conazole and the hypothesized mode of action for triadimefon-induced thyroid gland tumors was not supported by the data. PMID:17178690

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

3

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

PubMed

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. PMID:16248555

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

2005-11-01

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 Mice Treated with Hepatotumorigenic and Nonhepatotumorigenic Triazole Conazole Fungicides: Propiconazole, Triadimefon, and Myclobutanil  

Microsoft Academic Search

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

WILLIAM O. WARD; Don Delker; Susan Hester; Sheau-Fung Thai; Douglas Wolf; James Allen; Stephen Nesnow

2006-01-01

6

Transcriptional Profiles in Liver from Rats Treated with Tumorigenic and Non-tumorigenic Triazole Conazole Fungicides: Propiconazole, Triadimefon, and Myclobutanil  

Microsoft Academic Search

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

SUSAN D. HESTER; Douglas Wolf; Stephen Nesnow; Sheau-Fung Thai

2006-01-01

7

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

PubMed

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, propiconazole, and triadimefon, from the nontumorigenic myclobutanil. These findings serve to anchor other transcriptional profiling studies aimed at probing differences in key events and modes of action for tumorigenic and nontumorigenic conazoles. PMID:17178687

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

8

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

PubMed

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 resulted in a more complete description of the associated toxicological effects that can distinguish triadimefon from propiconazole and myclobutanil. PMID:17178689

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

2006-01-01

9

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

PubMed

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 gene expression profiles. PMID:17178688

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

2006-01-01

10

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...

11

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...

12

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...

13

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

PubMed

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. PMID:22822543

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

2012-06-01

14

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

Microsoft Academic Search

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

Amber K. Goetz; David J. Dix

2009-01-01

15

Inhibition of rat and human steroidogenesis by triazole antifungals.  

PubMed

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. PMID:19938956

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

2009-12-01

16

Interactions between the antifungal drug myclobutanil and gold and silver nanoparticles in Penicillium digitatum investigated by surface-enhanced Raman scattering.  

PubMed

Surface-enhanced Raman scattering (SERS) of an antifungal reagent, myclobutanil (MCB), was performed on Au and Ag nanoparticles (NPs) to estimate the drug-release behaviors in fungal cells. A density functional theory (DFT) calculation was introduced to predict a favorable binding site of MCB to either the Ag or Au atom. Myclobutanil was presumed to bind more strongly to Au than to Ag in their most stable, optimized geometries of the N4 atom in its 1,2,4-triazole unit binding to the metal atom. Strong intensities were observed in the Ag SERS spectra only at acidic pH values, whereas the most prominent peaks in the Au SERS spectra of MCB matched quite well with those of 1,2,4-triazole regardless of pH conditions. The Raman spectral intensities of the MCB-assembled Ag and Au NPs decreased after treatment with either potato dextrose agar (PDA) or glutathione (GSH). Darkfield microscopy and confocal SERS were performed to analyze the MCB-assembled metal NPs inside Penicillium digitatum fungal cells. The results suggested that MCB was released from the metal NPs in the intracellular GSH in the fungi because we observed only fungal cell peaks. PMID:24666947

Cho, Eun-Min; Singh, Dheeraj K; Ganbold, Erdene-Ochir; Dembereldorj, Uuriintuya; Jang, Seok-Won; Kim, Doseok; Choo, Jaebum; Kim, Sehun; Lee, Cheol Min; Yang, Sung Ik; Joo, Sang-Woo

2014-03-01

17

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...

18

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...

19

Enhancement of Acute Parathion Toxicity to Fathead Minnows Following Pre-exposure to Propiconazole  

Microsoft Academic Search

Over the past two decades a number of antifungal imidazole and triazole derivatives have been approved for use in agricultural applications. In a recent survey of pesticide concentrations in aquatic ecosystems of Central America, the antifungal triazole compound propiconazole was found to be the most widely distributed pesticide. The technical-grade formulation of propiconazole (TGP) has been shown to induce cytochrome

Steven L. Levine; James T. Oris

1999-01-01

20

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...

21

Induction of cytochrome P450 enzymes in rat liver by two conazoles, myclobutanil and triadimefon.  

PubMed

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 with the conazoles at three dose levels by gavage for 14 days: myclobutanil (150, 75, and 10mgkg(-1) body weight day(-1); triadimefon (115, 50, and 10 mg kg(-1) body weight day-'), which included their maximum tolerated dose levels (MTD). Both myclobutanil and triadimefon significantly induced pentoxyresorufin O-depentylase activities at their MTD levels: myclobutanil, 8.1-fold at 150mgkg(-1) body weight day- ; and triadimefon, 18.5-fold at 115mgkg(-1) body weight day-'. Benzyloxyresorufin O-debenzylase activities were similarly increased: myclobutanil, 13.3-fold; triadimefon, 27.7-fold. Quantitative real-time reverse-transcription polymerase chain reaction assays were used to characterize the mRNA expression of specific CYP genes induced by these two conazoles. Myclobutanil and triadimefon treatment at their MTD levels significantly increased rat hepatic mRNA expression of CYP2B1 (14.3- and 54.6-fold), CYP3A23/3A1 (2.2- and 7.3-fold), and CYP3A2 (1.5- and 1.7-fold). Western immunoblots of rat hepatic microsomal proteins identified significantly increased levels of CYP isoforms after myclobutanil or triadimefon treatment at their MTD levels: CYP2BI/2 (4.8- and 5.3-fold), and CYP3A1 (2.2- and 2.9-fold). Triadimefon also increased CYP3A2 immunoreactive protein levels 1.8-fold. These results indicate that triadimefon and myclobutanil, like other triazole-containing conazoles, induced CYP2B and CYP3A families of cytochromes in rat liver. PMID:17484520

Sun, G; Grindstaff, R D; Thai, S F; Lambert, G R; Tully, D B; Dix, D J; Nesnow, S

2007-02-01

22

40 CFR 180.443 - Myclobutanil; tolerances for residues.  

Code of Federal Regulations, 2010 CFR

...2009-07-01 2009-07-01 false Myclobutanil; tolerances for residues. 180...Specific Tolerances § 180.443 Myclobutanil; tolerances for residues. (a...for combined residues of the fungicide myclobutanil...

2009-07-01

23

40 CFR 180.443 - Myclobutanil; tolerances for residues.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Myclobutanil; tolerances for residues. 180...Specific Tolerances § 180.443 Myclobutanil; tolerances for residues. (a...for combined residues of the fungicide myclobutanil...

2010-07-01

24

Dissipation and residue of myclobutanil in lychee.  

PubMed

The dissipation and residue of myclobutanil in lychee under field conditions were studied. To determine myclobutanil residue in samples, an analytical method with a florisil column clean-up and detected by gas chromatography-electron capture detector (GC-ECD) was developed. Recoveries were found in the range of 83.24 %-89.00 % with relative standard deviations of 2.67 %-9.88 %. This method was successfully applied to analyze the dissipation and residue of myclobutanil in lychee in Guangdong and Guangxi Province, China. The half lives in lychee were from 2.2 to 3.4 days. The residues of myclobutanil in lychee flesh were all below the limit of quantification (LOQ) value (0.01 mg/kg), and most of the residues were concentrated in the peel. The terminal residues of myclobutanil were all bellow the maximum residue limit (MRL) value set by European Union (EU) (0.02 mg/kg). Hence it was safe for the use of this pesticide and the results also could give a reference for MRL setting of myclobutanil in lychee in China. PMID:22526985

Liu, Yanping; Sun, Haibin; Liu, Fengmao; Wang, Siwei

2012-06-01

25

Metabolism of myclobutanil and triadimefon by human and rat cytochrome P450 enzymes and liver microsomes.  

PubMed

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 was metabolized more rapidly than triadimefon, which is consistent with metabolism of the n-butyl side-chain in the former and the t-butyl group in the latter compound. Human and rat CYP2C and CYP3A enzymes were the most active. Metabolism was similar in microsomes prepared from livers of control and low-dose rats. High-dose (115 mg kg-1 day-1 of triadimefon or 150 mg kg-1 day-1 of myclobutanil) rats showed increased liver weight, induction of total CYP, and increased metabolism of the two triazoles, though the apparent Km appeared unchanged relative to the control. These data identify CYP enzymes important for the metabolization of these two triazoles. Estimated hepatic clearances suggest that CYP induction may have limited impact in vivo. PMID:16971344

Barton, H A; Tang, J; Sey, Y M; Stanko, J P; Murrell, R N; Rockett, J C; Dix, D J

2006-09-01

26

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

PubMed

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. PMID:23178453

Nesnow, Stephen

2012-11-23

27

Are insensitivities of Venturia inaequalis to myclobutanil and fenbuconazole correlated?  

Microsoft Academic Search

In the UK, two demethylation inhibitor (DMI) fungicides, myclobutanil and fenbuconazole, are recommended for controlling apple scab. Experiments were conducted to determine whether the sensitivity of V. inaequalis to myclobutanil was correlated with that to fenbuconazole. There was a marked reduction in the sensitivity of V. inaequalis to myclobutanil; averaged ED50 values increased from 0.338mg L?1 in the baseline population

X.-M. Xu; L.-Q. Gao; J.-R. Yang

2010-01-01

28

77 FR 75039 - Propiconazole; Pesticide Tolerances  

Federal Register 2010, 2011, 2012, 2013

...organ for propiconazole toxicity in animals is the liver. Increased liver weights were seen in mice after subchronic or chronic oral exposures to propiconazole. Liver lesions such as vacuolation of hepatocytes,...

2012-12-19

29

Mode of action for reproductive and hepatic toxicity inferred from a genomic study of triazole antifungals.  

PubMed

The mode of action for the reproductive toxicity of some triazole antifungals has been characterized as an increase in serum testosterone and hepatic response, and reduced insemination and fertility indices. In order to refine our mechanistic understanding of these potential modes of action, gene expression profiling was conducted on liver and testis from male Wistar Han IGS rats exposed to myclobutanil (500, 2000 ppm), propiconazole (500, 2500 ppm), or triadimefon (500, 1800 ppm) from gestation day six to postnatal day 92. Gene expression profiles indicated that all three triazoles significantly perturbed the fatty acid, steroid, and xenobiotic metabolism pathways in the male rat liver. In addition, triadimefon modulated expression of genes in the liver from the sterol biosynthesis pathway. Although expression of individual genes were affected, there were no common pathways modulated by all three triazoles in the testis. The pathways identified in the liver included numerous genes involved in phase I-III metabolism (Aldh1a1, Cyp1a1, Cyp2b2, Cyp3a1, Cyp3a2, Slco1a4, Udpgtr2), fatty acid metabolism (Cyp4a10, Pcx, Ppap2b), and steroid metabolism (Ugt1a1, Ugt2a1) for which expression was altered by the triazoles. These differentially expressed genes form part of a network involving lipid, sterol, and steroid homeostatic pathways regulated by the constitutive androstane (CAR), pregnane X (PXR), peroxisome proliferator-activated alpha, and other nuclear receptors in liver. These relatively high dose and long-term exposures to triazole antifungals appeared to perturb fatty acid and steroid metabolism in the male rat liver predominantly through the CAR and PXR signaling pathways. These toxicogenomic effects describe a plausible series of key events contributing to the disruption in steroid homeostasis and reproductive toxicity of select triazole antifungals. PMID:19423681

Goetz, Amber K; Dix, David J

2009-08-01

30

40 CFR 180.434 - Propiconazole; tolerances for residues.  

Code of Federal Regulations, 2010 CFR

...2009-07-01 2009-07-01 false Propiconazole; tolerances for residues. 180...Specific Tolerances § 180.434 Propiconazole; tolerances for residues. (a...tolerances are established for residues of propiconazole...

2009-07-01

31

40 CFR 180.434 - Propiconazole; tolerances for residues.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Propiconazole; tolerances for residues. 180...Specific Tolerances § 180.434 Propiconazole; tolerances for residues. (a...tolerances are established for residues of propiconazole...

2010-07-01

32

Bioavailability of butachlor and myclobutanil residues in soil to earthworms  

Microsoft Academic Search

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

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

2005-01-01

33

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...

34

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 (...

35

76 FR 27261 - Propiconazole; Pesticide Tolerances  

Federal Register 2010, 2011, 2012, 2013

...organ for propiconazole toxicity in animals is the liver. Increased liver weights were seen in mice after subchronic or chronic...50 milligrams/kilograms/day (mg/kg/day). Liver lesions such as vacuolation of hepatocytes,...

2011-05-11

36

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

PubMed

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. PMID:19409404

Goetz, Amber K; Dix, David J

2009-07-01

37

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...

38

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...

39

Theoretical study on ?-cyclodextrin inclusion complexes with propiconazole and protonated propiconazole  

PubMed Central

Summary The synthesis of the ?-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 ?-cyclodextrin/propiconazole and ?-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.

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

2012-01-01

40

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

PubMed

The synthesis of the ?-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 ?-cyclodextrin/propiconazole and ?-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. PMID:23365629

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

2012-01-01

41

Raman microscopy for the quantitation of propiconazole in white spruce  

Microsoft Academic Search

The Raman signature of propiconazole at 647–693 cm?1 was used to determine the propiconazole distribution in white spruce (Picea glauca). Samples treated with propiconazole were milled at ~1.5 mm intervals and analysed by methanol extraction and GC-MS to obtain\\u000a a depth profile in the longitudinal direction. The concentration of propiconazole in the milled wood layers ranged from 0.5\\u000a to 7.3 mg\\/g (dry mass

Erlet Kurti; D. V. Heyd; R. Stephen Wylie

2005-01-01

42

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...

43

Detection and management of myclobutanil-resistant grapevine powdery mildew (Uncinula necator) in Ontario  

Microsoft Academic Search

Myclobutanil-resistant Uncinula necator (Schwein.) Burrill was present in western New York State in 1995. In a vineyard in neighboring Ontario, myclobutanil gave poor control of powdery mildew during 1999. In 2000, mildew prevention was assessed with four management programs on three cultivars using small plot, randomized complete block designs. Programs received six fungicide applications between immediate prebloom and early ripening.

J. Northover; C. A. Homeyer

2001-01-01

44

Within-season distribution of myclobutanil resistance in populations of Venturia inaequalis in Virginia  

Microsoft Academic Search

Apple scab, caused by Venturia inaequalis (Vi), is a devastating disease of apple worldwide. Myclobutanil, a sterol-inhibiting (SI) fungicide, is commonly used to control apple scab in the eastern U.S. Populations of Vi in commercial apple orchards in Virginia have demonstrated resistance to myclobutanil and other SI fungicides, yet little is known about the nature and distribution of fungicide resistance

Sasha C. Marine; David G. Schmale; Keith S. Yoder

45

Study on Activities of Antioxidant Enzyme Induced by Myclobutanil in Danio rerio  

Microsoft Academic Search

In this study, the antioxidant responses induced by myclobutanil in zebrafish (Danio rerio) were analyzed. Changes in activities of superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) in the liver of fish were determined. The results showed that as myclobutanil concentration increased, significant changes in SOD and CAT activities and MDA level were found, suggesting that activities of enzymes mentioned

Feng Ding; Wenhua Song; Zhen Li; Jing Guo

2010-01-01

46

Decomposition of myclobutanil and triadimefon in grapes on the vines and during refrigerated storage  

Microsoft Academic Search

Decompositions of the triazole fungicides, myclobutanil and triadimefon, in table grapes, of a Greek variety, on the vines and during refrigerated storage, were studied. Vines of the Greek variety, Opsimo Edessas, were separately sprayed onto the vines with trade preparations of myclobutanil and triadimefon. Samples were collected from the vines after 1, 5, 11, 25, 35 and 46 days. Also,

Panagiotis E Athanasopoulos; Christos J Pappas; Nikolaos V Kyriakidis

2003-01-01

47

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

PubMed

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 pseudouridine. These results extended the companion transcriptomic and proteomic studies and provided a more complete understanding of propiconazole's effects in mouse liver. PMID:21278054

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

2011-04-01

48

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

Microsoft Academic Search

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

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

2010-01-01

49

Dissipation and residues of myclobutanil in tobacco and soil under field conditions.  

PubMed

Field experiments were conducted in two different locations to determine the dissipation pattern and residue levels of myclobutanil in tobacco leaves and soil. Myclobutanil 12.5 % microemulsion (ME) formulation was sprayed once at 3.0 mL/ha, and the residues in green tobacco leaves dissipated to more than 50 % of the initial deposits 5 days after application and up to above 90 % after 21 days. The dissipation rate of myclobutanil in soil was lower than that in green tobacco leaves. The residues dissipated above 50 % of the initial deposits 7 days after treatment and dissipated about 90 % after 42 days. The calculated half-life values (T (1/2)) were found to be 4.89-6.77 days in green tobacco leaves and 12.88-19.20 days in soil, respectively. The ultimate residues of myclobutanil in flue-cured tobacco leaves and soil were determined after the third and fourth applications at levels of 2.0 and 3.0 mL/ha. Myclobutanil residues in cured tobacco leaves 21 days after the last treatment ranged from 0.85 to 3.27 mg/kg. Meanwhile, the residues detected in soil reached below 0.045 mg/kg 21 days after the last treatment. PMID:22415649

Wang, Xiuguo; Li, Yiqiang; Xu, Guangjun; Sun, Huiqing; Xu, JinLi; Zheng, Xiao; Wang, Fenglong

2012-05-01

50

Interaction of propiconazole in the peanut leafspot disease complex  

SciTech Connect

(/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.

Hancock, H.G.

1985-01-01

51

Myclobutanil resistance in an isolate of Venturia inaequalis from New South Wales  

Microsoft Academic Search

An isolate of Venturia inaequalis from the Orange region of New South Wales had an ED50 of 0.97 ?g\\/mL for the fungicide myclobutanil. The ED50 indicative of resistance to this fungicide is ? 0.1 ?g\\/mL. This is the first record in Australia of V. inaequalis resistant to a Demethylation Inhibitor (DMI) fungicide.

S. D. Hetherington; D. A. Gunning

2003-01-01

52

Resistance to Myclobutanil in Populations of Venturia inaequalis in Winchester, Virginia  

Microsoft Academic Search

Sterol-inhibiting (SI) fungicides are widely used to manage apple scab, caused by Venturia inaequalis. However, recent observations indicate that populations of V. inaequalis in orchards in Virginia have developed resistance to myclobutanil and other SI fungicides. Little is known about the frequency and distribution of fungicide resistance in apple scab populations in Virginia. Isolates of V. inaequalis were collected from

Sasha C. Marine; David G. Schmale; Keith S. Yoder

2007-01-01

53

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...

54

Effects of fungicides triadimefon and propiconazole on soil bacterial communities.  

PubMed

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. PMID:20183078

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

2009-09-01

55

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

PubMed

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 17?-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. PMID:20708073

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

2010-12-01

56

Residue analysis and degradation studies of fenbuconazole and myclobutanil in strawberry by chiral high-performance liquid chromatography-tandem mass spectrometry.  

PubMed

A simple and sensitive enantioselective method for the determination of fenbuconazole and myclobutanil in strawberry was developed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Fenbuconazole and myclobutanil residues in strawberry were extracted with acetonitrile containing 1% acetic acid, and an aliquot was cleaned up with PSA (primary and secondary amine) and C(18) sorbent. The direct resolution of fenbuconazole and myclobutanil enantiomers was performed on a cellulose tris (3,5-dimethylphenylcarbamate) column using acetonitrile-0.1% formic acid solution (60:40, v/v) as the mobile phase. Quantification was achieved using matrix-matched standard calibration curves, and the limits of quantification for fenbuconazole and myclobutanil enantiomers in strawberry were both 2 ?g/kg. The method was successfully utilized to investigate the probable enantioselective degradation of fenbuconazole and myclobutanil in strawberry. The results showed that the degradation of the fenbuconazole and myclobutanil enantiomers in strawberry followed pseudofirst-order kinetics (R(2) > 0.97). The results from this study revealed that the degradation of fenbuconazole in strawberry was not enantioselective, while the degradation of myclobutanil was enantioselective, and the (+)-myclobutanil showed a faster degradation than (-)-myclobutanil in strawberry, resulting in the relative enrichment of (-)-myclobutanil in residue. The results could provide a reference to fully evaluate the risks of these two fungicides. PMID:21967215

Zhang, Hu; Wang, Xinquan; Qian, Mingrong; Wang, Xiangyun; Xu, Hao; Xu, Mingfei; Wang, Qiang

2011-11-23

57

The dissipation rates of myclobutanil and residue analysis in wheat and soil using gas chromatography-ion trap mass spectrometry  

Microsoft Academic Search

The dissipation of myclobutanil (triazole fungicide) in wheat plant, grain and soil under the local weather and soil conditions was studied and fungicide residues were determined by GC-ITMS. Myclobutanil (25% EC) was applied at two dosages, 60 g a.i. ha (recommended) and 120 g a.i. ha (2 times of the recommended dosage) in the experimental fields in Shandong, Beijing and

Xingang Liu; Fengshou Dong; Xu Wang; Yongquan Zheng

2009-01-01

58

Evaluation of Propiconazole Operational Treatments of Oaks for Wilt Control.  

National Technical Information Service (NTIS)

Oaks commercially treated with propiconazole on 29 sites in Minnesota in 1998 were evaluated for efficacy in controlling oak wilt. Root graft spread occurred in 39 percent of preventively treated red oaks over 5 years; spread in white oaks occurred only o...

J. Eggers J. Juzwik S. Bernick L. Mordaunt

2005-01-01

59

Toxicogenomic Study of Triazole Fungicides and Perfluoroalkyl Acids in Rat Livers Predicts Toxicity and Categorizes Chemicals Based on Mechanisms of Toxicity  

Microsoft Academic Search

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 triadime- fon) and two perfluorinated chemicals (perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS)) were administered daily via oral gavage for one, three, or five consecutive days to male Sprague-Dawley rats

Matthew T. Martin; Richard J. Brennan; Wenyue Hu; Eser Ayanoglu; Christopher Lau; Hongzu Ren; Carmen R. Wood; J. Christopher Corton; Robert J. Kavlock; David J. Dix

2007-01-01

60

Influence of lysozyme, yeast, azoxystrobin, and myclobutanil on fungal diseases of cucumbers grown hydroponically  

Microsoft Academic Search

The influence of hen egg white lysozyme (HEWL) on root rot caused by Pythium aphanidermatum, and of HEWL, yeast, azoxystrobin, and myclobutanil on stem canker caused by Botrytis cinerea and gummy stem blight caused by Didymella bryoniae in cucumber grown under near-commercial greenhouse conditions was studied. HEWL treatments applied as a root drench at 5g\\/l every 3 weeks gave a

R. Utkhede; C. Bogdanoff

2003-01-01

61

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

Microsoft Academic Search

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

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

2005-01-01

62

Environmental fate of the triazole fungicide propiconazole in a rice-paddy-soil lysimeter  

Microsoft Academic Search

Environmental fate of the triazole fungicide propiconazole, 1-[[2(2,4-dichlorophenyl)-4-propyl-1,3-diox olane-2-yl]methyl]1H-1,2,4-triazole, in soil was investigated using lysimeters simulating a rice-paddy-soil conditions. Two lysimeters composed of different soil types, a sandy loam (lysimeter A) and silty clay (lysimeter B), were used. Propiconazole (Tilt 250R EC) plus [U-14C]-propiconazole was applied over a two-year period to the soil surface of the lysimeters. Propiconazole fate in

In Seon Kim; Lee A. Beaudette; Jae Han Shim; Jack T Trevors; Yong Tack Suh

2002-01-01

63

Studies on adsorption of propiconazole on modified carbons  

Microsoft Academic Search

The adsorption capacity and kinetics of propiconazole in aqueous solution using untreated and treated activated carbons as adsorbents have been studied, providing new experimental data at different temperatures which were obtained using the bottle-point method. Untreated carbon was oxidized with HNO3, H2O2, NaOCl and NaOH to produce a series of samples with different surface chemical properties. The surface chemistry was

Olivier Adam; Maud Bitschené; Giangiacomo Torri; François De Giorgi; Pierre-Marie Badot; Grégorio Crini

2005-01-01

64

Effects of fungicides triadimefon and propiconazole on soil bacterial communities  

Microsoft Academic Search

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

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

2009-01-01

65

The toxicity of the fungicide propiconazole to soil flagellates  

Microsoft Academic Search

We investigated the effects of the ergosterol-inhibiting fungicide, propiconazole {1-[[2-(2,4-dichlorphenyl) - 4 - propyl\\u000a - 1,3 - dioxolan - 2 - yl]methyl] - 1H - 1,2,4 triazole; Tilt}, on mixed natural populations of bacterivorous and fungivorous flagellates in soil and on single\\u000a species of bacterivorous flagellates in liquid culture. The fungicide affected a mixed natural population of fungivorous flagellates\\u000a less

F. Ekelund; K. Westergaard; D. Søe

2000-01-01

66

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

PubMed

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. PMID:12455616

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

2002-09-01

67

Stacking and Sweeping in Cyclodextrin-Modified MEKC for Chiral Separation of Hexaconazole, Penconazole and Myclobutanil  

Microsoft Academic Search

A CD-MEKC method for the on-line preconcentration and chiral separation of three chiral triazole fungicides, namely hexaconazole,\\u000a penconazole and myclobutanil is reported. Simultaneous enantioseparation of the three triazole fungicides was successfully\\u000a achieved by the CD-MEKC system containing 40 mM HP-?-CD + 50 mM SDS in 25 mM phosphate buffer (pH 3.0) solution. Stacking\\u000a with a reverse migrating micelle (SRMM) and sweeping were then used in this

Wan Aini Wan Ibrahim; Dadan Hermawan; M. Marsin Sanagi; Hassan Y. Aboul-Enein

2010-01-01

68

The effects of a triazole fungicide, propiconazole, on pollen germination, tube growth and cytoskeletal distribution in Tradescantia virginiana  

Microsoft Academic Search

The effects of propiconazole on germination and tube growth of Tradescantia virginiana pollen when incorporated in germination media at 0, 102, 136, or 170 l l–1 were evaluated using light microscopy and immunocytochemistry. Propiconazole inhibited pollen germination, cytoplasmic streaming, and tube elongation. Treatments also induced abnormal tube morphology and cytoskeletal distribution. Tubes treated with propiconazole displayed weaker microfilament (Mf) signals

Yi He; Hazel Y. Wetzstein; Barry A. Palevitz

1995-01-01

69

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

Microsoft Academic Search

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

Pei-Jen Chen; Tanya Moore; Stephen Nesnow

2008-01-01

70

The effect of propiconazole on foliar fungal diseases, herbage yield and quality of perennial ryegrass  

Microsoft Academic Search

The fungicide propiconazole, applied as a foliar spray to swards of perennial ryegrass (Lolium perenne) at four sites in England from 1990 to 1992, reduced the incidence of powdery mildew (Blumeria graminis), Drechslera leaf spot (Drechslera spp.) and Rhynchosporium leaf blotch (Rhynchosporium spp.), increased the number of leaves per tiller and reduced the proportion of dead leaves. Propiconazole increased yield,

G. C. Lewis; R. H. Lavender; T. M. Martyn

1996-01-01

71

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...

72

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...

73

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 ...

74

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...

75

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...

76

Cyclodextrin-modified MEKC for enantioseparation of hexaconazole, penconazole, and myclobutanil.  

PubMed

A CD-modified micellar EKC (CD-MEKC) method with 2-hydroxypropyl-gamma-CD (HP-gamma-CD) as chiral selector for the enantioseparation of three chiral triazole fungicides, namely hexaconazole, penconazole, and myclobutanil, is reported for the first time. Simultaneous enantioseparation of the three triazole fungicides was successfully achieved using a CD-MEKC system containing 40 mM HP-gamma-CD and 50 mM SDS in 25 mM phosphate buffer (pH 3.0) solution with resolutions (R(s)) greater than 1.60, peak efficiencies (N) greater than 200,000 for all enantiomers and an analysis time within 15 min compared to 36 min as previously reported using sulfated-beta-CD. PMID:19142910

Wan Ibrahim, Wan Aini; Hermawan, Dadan; Sanagi, M Marsin; Aboul-Enein, Hassan Y

2009-02-01

77

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...

78

Formation and Structure of Metal Complexes with the Fungicides Tebuconazole and Propiconazole  

Microsoft Academic Search

Divalent copper and zinc complexes with metal:azole ratio 1?2 were readily formed at room temperature with the fungicides tebuconazole and propiconazole. The structure of copper and zinc tebuconazole acetate and zinc cis?propiconazole chloride were examined by X?ray crystallography. In copper tebuconazole acetate, the copper atom lies on a crystallographic inversion center and is coordinated to two triazole and two acetate

Philip D. Evans; Karl J. Schmalzl; Craig M. Forsyth; Gary D. Fallon; Siegbert Schmid; Beate Bendixen; Sigurd Heimdal

2007-01-01

79

Effect of propiconazole on growth and sterol biosynthesis by Sclerotium rolfsii  

Microsoft Academic Search

Germination of sclerotia ofSclerotium rolfsii on agar nutrient medium was delayed or slightly inhibited by concentrations of propiconazole between 0.4 and 4.0 ?g ml?1, but was strongly inhibited by 8 ?g ml?1 and completely inhibited by 16 ?g ml?1. On the other hand, growth of hyphae from the germinated sclerotia was strongly inhibited by propiconazole at 1 ?g ml?1 or

W. F. Waterfield; H. D. Sisler

1989-01-01

80

Evaluation of solid sorbents for the determination of fenhexamid, metalaxyl-M, pyrimethanil, malathion and myclobutanil residues in air samples  

Microsoft Academic Search

A methodology is described for greenhouse air analysis by sampling fenhexamid, pyrimethanil, malathion, metalaxyl-M and myclobutanil in solid sorbents. Pesticides were determined by gas chromatography with NP Detector. The trapping efficiency of XAD-2, XAD-4, Supelpak-2, Florisil and C-18 at different sampling conditions (rate, time and air humidity) and pesticides concentration levels has been evaluated. No breakthrough was observed in the

Nikolaos G. Tsiropoulos; Evangelos B. Bakeas; Vasilios Raptis; Stavroula S. Batistatou

2006-01-01

81

Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish.  

PubMed

Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor ?1 (rar?1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish populations in the aquatic environment. PMID:24962053

Lin, Chun-Hung; Chou, Pei-Hsin; Chen, Pei-Jen

2014-07-30

82

Synthesis and antifungal activities of trichodermin derivatives as fungicides on rice.  

PubMed

Twenty new trichodermin derivatives, 2a-5, containing alkoxy, acyloxy, and Br groups in 4-, 8-, 9-, 10- and 16-positions were synthesized and characterized. The antifungal activities of the new compounds against rice false smut (Ustilaginoidea virens), rice sheath blight (Rhizoctonia solani), and rice blast (Magnaporthe grisea) were evaluated. The results of bioassays indicated that the antifungal activities were particularly susceptible to changes at 4-, 8-, and 16-positions, but low to changes at 9- and 10-positions. Most of these target compounds exhibited good antifungal activities at the concentration of 50?mg?l(-1) . Compound 4 (9-formyltrichodermin; EC50 0.80?mg?l(-1) ) with an CHO group at 9-position displayed nearly the same level of antifungal activity against Ustilaginoidea virens as the commercial fungicide prochloraz (EC50 0.82?mg?l(-1) ), while compound 3f ((8R)-8-{[(E)-3-phenylprop-2-enoyl]oxy}trichodermin; EC50 3.58 and 0.74?mg?l(-1) ) with a cinnamyloxy group at C(8) exhibited much higher antifungal activities against Rhizoctonia solani and Magnaporthe grisea than the commercial fungicides prochloraz (EC50 0.96?mg?l(-1) ) and propiconazole (EC50 5.92?mg?l(-1) ), respectively. These data reveal that compounds 3f and 4 possess high antifungal activities and may serve as lead compounds for the development of fungicides in the future. PMID:23576346

Xu, Xiaojun; Cheng, Jingli; Zhou, Yong; Zhang, Chulong; Ou, Xiaoming; Su, Weike; Zhao, Jinhao; Zhu, Guonian

2013-04-01

83

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

PubMed

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. PMID:20839933

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

2010-10-01

84

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

PubMed

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

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

2012-02-29

85

Effect of propiconazole and difenoconazole on the control of anthracnose of chilli fruits caused by Colletotrichum capsici  

Microsoft Academic Search

Anthracnose of chillies caused by Colletotrichum capsici is a serious disease affecting the yield and quality of fruits. In vitro, greenhouse and field experiments were conducted to evaluate the efficacy of propiconazole, difenoconazole and carbendazim at different concentrations to control the pathogen and disease incidence. Among the fungicides, propiconazole exhibited the highest level of inhibition of in vitro mycelial growth,

K. Gopinath; N. V. Radhakrishnan; J. Jayaraj

2006-01-01

86

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

Microsoft Academic Search

A method for the chiral separation of propiconazole using cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) with hydroxypropyl-?-cyclodextrin (HP-?-CD) as chiral selector is reported. The use of a mixture of 30mM HP-?-CD, 50mM SDS, methanol–acetonitrile 10%:5% (v\\/v) in 25mM 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

Wan Aini Wan Ibrahim; Dadan Hermawan; Mohd Marsin Sanagi

2007-01-01

87

Pediatric Antifungal Agents  

PubMed Central

Purpose of review In immunocompromised hosts, invasive fungal infections are common and fatal. In the past decade, the antifungal armamentarium against invasive mycoses has expanded greatly. The purpose of this report is to review the most recent literature addressing the use of antifungal agents in children. Recent findings Most studies evaluating the safety and efficacy of antifungal agents are limited to adults. However, important progress has been made in describing the pharmacokinetics and safety of newer antifungal agents in children, including the echinocandins. Summary Dosage guidelines for newer antifungal agents are currently based on adult and limited pediatric data. Because important developmental pharmacology changes occur throughout childhood impacting the pharmacokinetics of these agents, antifungal studies specifically designed for children are necessary.

Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Smith, P Brian

2009-01-01

88

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 ...

89

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...

90

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...

91

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

PubMed

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 14?-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. PMID:22239944

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

2012-04-01

92

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

Microsoft Academic Search

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 15mgl?1 PCZ alone and

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

2007-01-01

93

Relative efficacy of paclobutrazol, propiconazole and tetraconazole as stress protectants in wheat seedlings  

Microsoft Academic Search

The stress protective effects of triazoles including paclobutrazol, a plant growth regulator, and two fungicides, propiconazole and tetraconazole, are compared. Wheat (Triticum aestivum L. cv Katepwa) seeds were imbibed for 18 h in distilled water (Ck) or in aqueous solutions of each triazole (50 mg L-1). Seeds were then air dried, planted in sectioned plastic flats and grown in a

Angela Gilley; R. A. Fletcher

1997-01-01

94

Relative virulence of isolates of Sclerotinia homoeocarpa with varying sensitivity to propiconazole  

Microsoft Academic Search

Isolates of Sclerotinia homoeocarpawere collected from across southern Ontario from areas where demethylation inhibiting fungicides reportedly had never been used. Forty of these isolates with propiconazole EC 50 values ranging from 0.003 to 0.069 gm l 1 were inoculated onto creeping bentgrass (Agrostis palustris) in summer 1995 and summer 1996 to assess virulence. Each isolate was grown on mixed cereal

Tom Hsiang; Lin Yang; Wayne Barton

1998-01-01

95

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

PubMed

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. PMID:18945160

Romero, R A; Sutton, T B

1997-01-01

96

Enantiomeric determination of azole antifungals in wastewater and sludge by liquid chromatography-tandem mass spectrometry.  

PubMed

A sensitive and reliable liquid chromatographic-tandem mass spectrometric method for enantiomeric determination of five chiral azole antifungals (econazole, ketoconazole, miconazole, tebuconazole, and propiconazole) in wastewater and sludge has been established and validated. An isotope-labeled internal standard was used for quantification. Recovery of the individual enantiomers was usually in the range of 77-102 % for wastewater and 71-95 % for sludge, with relative standard deviations within 20 %. No significant difference (p>0.05) was observed between recovery of pairs of enantiomers of the chiral azole antifungals except for those of tebuconazole. Method quantification limits for individual enantiomers were 0.3-10 ng L(-1) and 3-29 ng g(-1) dry weight for wastewater and sludge, respectively. The method was used to investigate the enantiomeric composition of the azole pharmaceuticals in wastewater and sludge samples from a sewage treatment plant in China. Enantiomers of miconazole, ketoconazole, and econazole were widely detected. The results showed that the azole antifungals in wastewater and sludge were generally racemic or marginally non-racemic. The method is a useful tool for investigation of the enantiomeric occurrence, behavior, and fate of the chiral azole antifungals in the environment. PMID:22526654

Huang, Qiuxin; Zhang, Kun; Wang, Zhifang; Wang, Chunwei; Peng, Xianzhi

2012-06-01

97

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 ...

98

Effects of propiconazole on extra-cellular enzymes involved in nutrient mobilization during Trametes versicolor wood colonization  

Microsoft Academic Search

The effects of propiconazole on extra-cellular enzyme levels in Trametes versicolor have been investigated during wood colonization and degradation. The working hypothesis was that the biocide could alter\\u000a metabolic pathways, which could lead to an alteration of extra-cellular enzyme production. In the presence of a propiconazole\\u000a sub-lethal concentration, the wood degradation rate decrease concomitantly with the lag phase of fungal

Serge Lekounougou; Jean-Pierre Jacquot; Philippe Gérardin; Eric Gelhaye

2008-01-01

99

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

PubMed

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 (GST?) 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 GST? 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 ROS form. PMID:21864511

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

100

Specific adsorption of propiconazole and humic acid on Pt and PtO films  

Microsoft Academic Search

We herein report a study of specific adsorption of propiconazole (PPC) and humic acid (HM) on Pt and PtO films, using cyclic voltammetry (CV) and cyclic massogram (CM) in 0.5M H2SO4. This approach serves as an alternative to studies involving specific adsorption on soil minerals (e.g., clays, Al\\/Fe oxides), in which adsorption is evaluated by conducting batch or column sorption

Andréia P. Silva; Sandra S. Marqueti; Gilberto Maia

2009-01-01

101

Soil applied propiconazole alleviates the impact of salinity on Catharanthus roseus by improving antioxidant status  

Microsoft Academic Search

An investigation was carried out to estimate the salt stress ameliorative effect of propiconazole (a triazole group of fungicide cum plant growth regulator) on the NaCl stressed Catharanthus roseus. The experiment was conducted in pots. All the pots were irrigated to the field capacity with ground water up to 30 days after sowing (DAS). The treatments were given as 80mM

C. Abdul Jaleel; R. Gopi; P. Manivannan; M. Gomathinayagam; P. V. Murali; R. Panneerselvam

2008-01-01

102

Propiconazole and Dietary Components as Specific Inducers of Glutathione S-Transferases in Orthosia gothica  

Microsoft Academic Search

Six major glutathione S-transferase (GST) subunits (subunits 1-6), belonging to two different GST classes (GST1 and GST2), were purified by glutathione-Sepharose affinity chromatography and reverse-phase high-performance liquid chromatography (HPLC) from the gut-free soft tissue cytosol of last instar Orthosia gothica fed a bean diet (large white kidney beans) to which propiconazole (250 ppm) had been added for 2 days. Subunit

E. Egaas

1995-01-01

103

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

Microsoft Academic Search

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

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

2006-01-01

104

PROPICONAZOLE AS A TREATMENT FOR OAK WILT IN QUERCUS RUBRA AND Q. ELLIPSOIDALIS  

Microsoft Academic Search

In Minnesota, propiconazole was injected into mature Quercus rubraand Q. e\\/\\/\\/pso\\/tfa\\/\\/sat high risk to natural infection with Ceratocystis fagacearum, the oak wilt fungus. The trees were treated preventively in 1989 and 1990 at a constant rate of 0.168 g a.i.\\/cm dbh using a root flare injection technique. Control trees were left untreated. Since 1989,15 of 49 trees treated in 1989

N. K. Osterbauer; D. W. French

105

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

PubMed

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 generally, this work could contribute to investigate the toxicity of agricultural chemicals on AMF and underlined the emergency of using sustainable alternative method to control plant diseases. Furthermore, these data can provide a useful approach in soil ecotoxicology studies and risk assessment. PMID:22702206

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

2011-01-01

106

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

PubMed

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 activation, metabolism of xenobiotics, metabolism of biochemical intermediates, biosynthesis of biochemical intermediates, and oxidative stress in mouse liver. The present study provides novel insights into toxic mechanisms and/or modes of action of propiconazole which are required for human health risk assessment of this environmental chemical. PMID:20095644

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

2010-03-01

107

Determination of imidacloprid, metalaxyl, myclobutanil, propham, and thiabendazole in fruits and vegetables by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry  

Microsoft Academic Search

Imidacloprid, metalaxyl, myclobutanil, propham, and thiabendazole have been simultaneously determined in strawberries, oranges, potatoes, pears, and melons by matrix solid-phase dispersion (MSPD) followed by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) in positive-ion mode. The samples were homogenized with C8 bonded silica as MSPD sorbent, placed in a glass column, and eluted with dichloromethane. Chromatographic separation of the compounds was

Ximo Pous; Yolanda Picó

2001-01-01

108

Simultaneous Analysis of Hexaconazole, Myclobutanil, and Tebuconazole Residues in Apples and Soil by SPE Clean-Up and GC with Nitrogen–Phosphorus Detection  

Microsoft Academic Search

A facile and sensitive method utilizing capillary gas chromatography with nitrogen phosphorus detection (GC–NPD) has been\\u000a developed and validated for simultaneous analysis of hexaconazole, myclobutanil, and tebuconazole, three broad-spectrum systemic\\u000a fungicides, in apples and soil. Two samples were fortified with the three pesticides and subjected to ultrasonic extraction,\\u000a followed by solid-phase extraction (SPE) to remove coextractives, before analysis by GC–NPD.

Zhubo Deng; Jiye Hu; Dongmei Qin; Hui Li

2010-01-01

109

New topical antifungal drugs.  

PubMed

The new antifungal drugs used for topical treatment of superficial, skin and mucosal mycoses are reviewed. Amorolfine and allylamines (naftifine and terbinafine) are promising original molecules with new and different modes of action against fungi. Rilopirox is a new pyridone derivative under study. A great number of azole derivatives, such as oxiconazole, isoconazole, sulconazole, and terconazole, are used as topical antifungals. Three of them are synthesized in Barcelona by pharmaceutical laboratories: sertaconazole, flutrimazole and eberconazole. All of them are now in the register process for commercialization. The combination of antifungals with active products, such as keratoplastics, is used mainly for the treatment of onychomycoses; 40% urea associated with 1% bifonazole has shown high efficacy for this indication. PMID:8118161

Torres-Rodríguez, J M

1993-01-01

110

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 ...

111

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...

112

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

PubMed

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. PMID:10563888

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

1999-01-01

113

Antifungal activity of diethyldithiocarbamate.  

PubMed

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. PMID:2555712

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

1989-10-01

114

Determination of commonly used azole antifungals in various waters and sewage sludge using ultra-high performance liquid chromatography-tandem mass spectrometry.  

PubMed

Sensitive and reliable methods have been developed and validated for determination of commonly consumed azole antifungal pharmaceuticals (clotrimazole, econazole, ketoconazole, and miconazole) and biocides (propiconazole and tebuconazole) in various waters and sewage sludge. Solid phase extraction (SPE) combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to determine the azole antifungals in waters. Azole antifungals in sewage sludge were extracted with ultrasonic-assisted extraction, followed by SPE cleanup and UHPLC-MS/MS detection. Quantification was performed by internal standard calibration in multiple reaction monitoring mode. Recoveries were mostly in the range of 52-110% with relative standard deviations generally within 20%. Method quantification limits were 0.5-6 ng L(-1) in waters and 3-9 ng g(-1) dry weight (dw) in sewage sludge, respectively. The methods were applied to determine the azole antifungals in wastewater, river water, sediment, and sewage sludge sampled from the Pearl River Delta, China. Clotrimazole, ketoconazole, and miconazole were widely detected at low ng L(-1) in waters, low ng g(-1) dw in river sediment, and low microg g(-1) dw in sewage sludge. The methods can provide valuable tools for investigating occurrence and fate of the azole antifungals in the environment. PMID:20381052

Huang, Qiuxin; Yu, Yiyi; Tang, Caiming; Peng, Xianzhi

2010-05-21

115

Trends in antifungal research  

Microsoft Academic Search

\\u000a With the increasing use of aggressive immunosuppressive therapies in the management of a variety of patient populations, the\\u000a continuing presence of the AIDS pandemic and the therapeutic advances employed in critical care settings, an increasing number\\u000a of serious fungal infections are being encountered by today’s practicing clinicians. Traditionally, antifungal drug therapy\\u000a has been delivered by means of intravenous infusion, oral

Vorapann Mahaguna; Robert O. Williams; Thomas C. Hardin

116

Association of the Fungicide Propiconazole with Size Fractionated Material from a Silty Clay Soil – S.E. Norway  

Microsoft Academic Search

Eroded soil material may be an important transporting agent for pesticides that are strongly sorbed to soil. The abilityof the fungicide propiconazole to interact with colloidal andparticulate materials has been studied by means of sorptionand desorption experiments. Size separation of silty clay soilfrom Mørdre, Norway and subsequent characterization showedthat different size fractions of soil possessed different physical and chemical properties

G. Riise; H. Madsen; T. Krogstad; M. Nandrup Pettersen

2001-01-01

117

Antifungal Lock Therapy  

PubMed Central

The widespread use of intravascular devices, such as central venous and hemodialysis catheters, in the past 2 decades has paralleled the increasing incidence of catheter-related bloodstream infections (CR-BSIs). Candida albicans is the fourth leading cause of hospital-associated BSIs. The propensity of C. albicans to form biofilms on these catheters has made these infections difficult to treat due to multiple factors, including increased resistance to antifungal agents. Thus, curing CR-BSIs caused by Candida species usually requires catheter removal in addition to systemic antifungal therapy. Alternatively, antimicrobial lock therapy has received significant interest and shown promise as a strategy to treat CR-BSIs due to Candida species. The existing in vitro, animal, and patient data for treatment of Candida-related CR-BSIs are reviewed. The most promising antifungal lock therapy (AfLT) strategies include use of amphotericin, ethanol, or echinocandins. Clinical trials are needed to further define the safety and efficacy of AfLT.

Walraven, Carla J.

2013-01-01

118

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

PubMed

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 fractions from control, MVAL or propiconazole-treated cells revealed increased Ras protein in the cytoplasmic fraction of L-744,832-treated cells, while propiconazole or MVAL reversed these effects. Western blot analysis indicated that phosphorylation of Erk1/2, a protein downstream of Ras, was increased by propiconazole. These data indicate that propiconazole increases cell proliferation by increasing the levels of cholesterol biosynthesis intermediates presumably through a negative feedback mechanism within the pathway, a result of CYP51 inhibition. This feedback mechanism increases Erk1/2 signaling through mevalonate-mediated Ras activation. These results provide an explanation for the observed effects of propiconazole on hepatic cholesterol pathways and on the increased hepatic cell proliferation induced by propiconazole in mice. PMID:22361350

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

2012-04-15

119

Antifungal constituent from Gordonia dassanayakei.  

PubMed

The hexane extract of the stem bark of Gordonia dassanayakei showed high antifungal activity against plant pathogenic fungi Curvularia sp., Colletotrichum gloeosporioides, Rhizoctonia solani, Corynespora cassiicola, and Fusarium sp. A compound responsible for the antifungal activity was isolated and identified as 3-formyl-2,4-dihydroxy-6-methylbenzoic acid 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl ester (1). PMID:11429257

Athukoralage, P S; Herath, H M; Deraniyagala, S A; Wijesundera, R L; Weerasinghe, P A

2001-06-01

120

Issues in antifungal susceptibility testing  

Microsoft Academic Search

In line with the availability of an increasing array of systemic antifungal agents, there is a need for accurate, reproducible and predictive susceptibility testing of fungal isolates in order to help inform clinical choice. Much early attention on antifungal susceptibility testing focused on defining test par- ameters that produced reproducible and reliable intra- and inter-laboratory results and there are now

Elizabeth M. Johnson

2008-01-01

121

Antifungal Susceptibility testing: New trends  

Microsoft Academic Search

Development of standardized antifungal susceptibility testing methods has been the focus of intensive research in the last 15 years. Antifungal sensitivity tests were done for selected (46) fungal isolates, (23 dermatophytes and 23 Candida ) by E-test and broth microdilution method. E- test gave better sensitivity results on Candida species than dermatophytes for all drugs expect itraconazole. We compared E-test

Amina Mostafa; Abdel Aal; Mohamed M. Taha; Noha El-Mashad; Walaa El-Shabrawy

122

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

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 fractions from control, MVAL or propiconazole-treated cells revealed increased Ras protein in the cytoplasmic fraction of L-744,832-treated cells, while propiconazole or MVAL reversed these effects. Western blot analysis indicated that phosphorylation of Erk1/2, a protein downstream of Ras, was increased by propiconazole. These data indicate that propiconazole increases cell proliferation by increasing the levels of cholesterol biosynthesis intermediates presumably through a negative feedback mechanism within the pathway, a result of CYP51 inhibition. This feedback mechanism increases Erk1/2 signaling through mevalonate-mediated Ras activation. These results provide an explanation for the observed effects of propiconazole on hepatic cholesterol pathways and on the increased hepatic cell proliferation induced by propiconazole in mice. Highlights: ? Propiconazole increases cell proliferation in AML12 mouse hepatocytes. ? Propiconazole increases Ras farnesylation and alters Ras membrane localization. ? Propiconazole increases Erk1/2 phosphorylation. ? Dysregulation of the cholesterol biosynthesis pathway can explain these results. ? These results can explain similar effects induced by propiconazole in mice.

Murphy, Lynea A.; Moore, Tanya; Nesnow, Stephen, E-mail: nesnow.stephen@epa.gov

2012-04-15

123

Determination of imidacloprid, metalaxyl, myclobutanil, propham, and thiabendazole in fruits and vegetables by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry.  

PubMed

Imidacloprid, metalaxyl, myclobutanil, propham, and thiabendazole have been simultaneously determined in strawberries, oranges, potatoes, pears, and melons by matrix solid-phase dispersion (MSPD) followed by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) in positive-ion mode. The samples were homogenized with C8 bonded silica as MSPD sorbent, placed in a glass column, and eluted with dichloromethane. Chromatographic separation of the compounds was achieved on a reversed-phase LC column using a methanol-ammonium formate (50 mmol L(-1)) gradient as a mobile phase. Samples were screened by monitoring the protonated molecular ion at m/z 256 for imidacloprid, 280 for metalaxyl, 289 for myclobutanil, and 202 for thiabendazole, and the main fragment at m/z 138 for propham. Positive samples were confirmed by multiple-ion monitoring. The repeatability (<20%) and recovery (>57%) of the method were good, and limits of detection (<0.05 mg kg(-1)) were adequate. PMID:11678189

Pous, X; Ruíz, M J; Picó, Y; Font, G

2001-09-01

124

Effect of Turfgrass Cover and Irrigation on Soil Mobility and Dissipation of Mefenoxam and Propiconazole  

Microsoft Academic Search

conducted on turfgrass versus bare soil. The interaction of irrigation practices and the presence of turfgrass on the mobility and dissipation (methoxyacetyl)-DL-alanine methyl ester), pendimethalin of mefenoxam (N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-D-alanine (N-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzenamine), methyl ester) and propiconazole (1-((2-(2,4-dichlorophenyl)-4-pro- chlorpyrifos (O,O-diethyl-O-(3,5,6-trichloro-2-pyridinyl) pyl-1,3-dioxolan-2-yl)methyl)-1H-1,2,4-triazole) was studied. Sam- phosphorothioate), and isazofos (O-5-chloro-1-isopropyl- pling cylinders (20-cm diam.) were placed in either creeping bentgrass 1H-1,2,4-triazol-3-yl O,O-diethylphosphorothioate) ap- (Agrostis stolonifera L.

D. S. Gardner; B. E. Branham

2001-01-01

125

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

Microsoft Academic Search

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?gL?1) for 7, 20 and 30d. Multiple biomarkers were measured, including hematological indices (hemoglobin concentration, red

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

2011-01-01

126

Antifungal activity of Terminalia australis.  

PubMed

Dichloromethane, methanol and aqueous extracts of the aerial parts of Terminalia australis were evaluated for their antifungal activity. The methanol and aqueous extracts were found to be effective against the tested Aspergillus and Candida strains. PMID:12727498

Carpano, Stella M; Spegazzini, Etile D; Rossi, Javier S; Castro, Maria T; Debenedetti, Silvia L

2003-04-01

127

Antifungal macrodiolide from Streptomyces sp.  

PubMed Central

Aerobic fermentation cultures of Streptomyces sp. produced an antifungal macrodiolide. This new antibiotic consists of two units of homononactic acid linked to form a cyclic diester. An unknown polypeptide was also isolated in trace quantities. The antibiotic with polypeptide complex showed high levels of antifungal activity compared with that of the macrodiolide alone. The macrodiolide also showed a stimulatory effect on some species of fungi. The production, purification, and characterization of these compounds are reported.

Jois, H R; Sarkar, A; Gurusiddaiah, S

1986-01-01

128

Antifungal therapy with an emphasis on biofilms.  

PubMed

Fungal infections are on the rise as advances in modern medicine prolong the lives of severely ill patients. Fungi are eukaryotic organisms and there are a limited number of targets for antifungal drug development; as a result the antifungal arsenal is exceedingly limited. Azoles, polyenes and echinocandins constitute the mainstay of antifungal therapy for patients with life-threatening mycoses. One of the main factors complicating antifungal therapy is the formation of fungal biofilms, microbial communities displaying resistance to most antifungal agents. A better understanding of fungal biofilms provides for new opportunities for the development of urgently needed novel antifungal agents and strategies. PMID:24011516

Pierce, Christopher G; Srinivasan, Anand; Uppuluri, Priya; Ramasubramanian, Anand K; López-Ribot, José L

2013-10-01

129

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...

130

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

PubMed Central

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.

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

2012-01-01

131

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

PubMed

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 TGF?-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. PMID:22334560

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

2012-05-01

132

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

PubMed

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. PMID:21384499

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

2013-03-01

133

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

PubMed

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. PMID:22329022

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

2012-01-01

134

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

PubMed

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. PMID:22590578

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

2012-01-01

135

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

PubMed

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 ?H and ?S 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. PMID:21702493

Wang, Chao; Li, Ying

2011-08-10

136

Antifungal peptides at membrane interaction.  

PubMed

Many drugs are available for the treatment of systemic or superficial mycoses, but only a limited number of them are effective antifungal drugs, devoid of toxic and undesirable side effects. Furthermore, resistance development and fungistatic rather than fungicidal activities represent limitations of current antifungal therapy. Therefore an urgent need for a new generation of antifungal agents remains. We recently synthesised a set of linear and cyclic peptides characterized by sequences typical of membrane-active antimicrobial peptides (AMP). AMT2, cyclo-AMT2, AMT3 and cyclo-AMT3 (Scheme 1) were tested against different yeast species and exhibited general antifungal activity, with a specificity against Cryptococcus neoformans. To evaluate the role of the membrane cell in the mechanism of antifungal activity, we investigated the conformational behaviour of AMT2, cyclo-AMT2, AMT3 and cyclo-AMT3 in different bio-membrane mimicking systems using a combined approach based on spectroscopy and microscopy techniques. Our data highlight the behaviour of the peptides to interact with the bilayer surface, excluding their ability to destabilize or permeabilize the fungal cell wall. Microbial membrane, indeed, may be an important platform for specific interactions of peptides with specific targets involved in the cell wall synthesis. PMID:22417640

Di Marino, Sara; Scrima, Mario; Grimaldi, Manuela; D'Errico, Gerardino; Vitiello, Giuseppe; Sanguinetti, Maurizio; De Rosa, Margherita; Soriente, Annunziata; Novellino, Ettore; D'Ursi, Anna Maria

2012-05-01

137

Evaluation of vaginal antifungal formulations in vivo.  

PubMed Central

Relatively simple and rapid procedures have been developed for evaluating the local efficacy of vaginal antifungal agents in vivo in a vaginal candidiasis model in ovariectomized rats. The results of this investigation indicate that the model and methods described are quite suitable for screening potential antifungal substances and for assessing the chemotherapeutic effectiveness of new antifungal agents and formulations before carrying out clinical studies.

McRipley, R. J.; Erhard, P. J.; Schwind, R. A.; Whitney, R. R.

1979-01-01

138

Alternative approaches to antifungal therapies  

PubMed Central

The expansive use of immunosuppressive medications in fields such as transplantational medicine and oncology, the higher frequency of invasive procedures in an aging population and the HIV/AIDS pandemic have increased the frequency of systemic fungal infections. At the same time, increased resistance of pathogenic fungi to classical antifungal agents has led to sustained research efforts targeting alternative antifungal strategies. In this review, we focus on two promising approaches: cationic peptides and the targeting of fungal virulence factors. Cationic peptides are small, predominantly positively charged protein fragments which exert direct and indirect antifungal activities, one mechanism of action being the permeabilization of the fungal membrane. They include lysozyme, defensins, and cathelicidins, as well as novel synthetic peptides. Amongst fungal virulence factors, the targeting of candidal secreted aspartic proteinases seems to be a particularly promising approach.

Mehra, T; Koberle, M; Braunsdorf, C; Mailander-Sanchez, D; Borelli, C; Schaller, M

2012-01-01

139

Comparison of echinocandin antifungals  

PubMed Central

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.

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

2007-01-01

140

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

Microsoft Academic Search

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

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

1999-01-01

141

Antifungal resistance in yeast vaginitis.  

PubMed Central

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.

Dun, E.

1999-01-01

142

Antifungal application of nonantifungal drugs.  

PubMed

Candida species are the cause of 60% of all mycoses in immunosuppressed individuals, leading to ?150,000 deaths annually due to systemic infections, whereas the current antifungal therapies either have toxic side effects or are insufficiently efficient. We performed a screening of two compound libraries, the Enzo and the Institute for Molecular Medicine Finland (FIMM) oncology collection library, for anti-Candida activity based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. From a total of 844 drugs, 26 agents showed activity against Candida albicans. Of those, 12 were standard antifungal drugs (SADs) and 7 were off-target drugs previously reported to be active against Candida spp. The remaining 7 off-target drugs, amonafide, tosedostat, megestrol acetate, melengestrol acetate, stanozolol, trifluperidol, and haloperidol, were identified with this screen. The anti-Candida activities of the new agents were investigated by three individual assays using optical density, ATP levels, and microscopy. The antifungal activities of these drugs were comparable to those of the SADs found in the screen. The aminopeptidase inhibitor tosedostat, which is currently in a clinical trial phase for anticancer therapy, displayed a broad antifungal activity against different Candida spp., including Candida glabrata. Thus, this screen reveals agents that were previously unknown to be anti-Candida agents, which allows for the design of novel therapies against invasive candidiasis. PMID:24277040

Stylianou, Marios; Kulesskiy, Evgeny; Lopes, José Pedro; Granlund, Margareta; Wennerberg, Krister; Urban, Constantin F

2014-02-01

143

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 ...

144

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

PubMed Central

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 t1/2 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.

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

2011-01-01

145

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

PubMed

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. PMID:21909317

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

2011-08-01

146

Antifungal activity of rhizospheric bacteria.  

PubMed

Fluorescent Pseudomonad spp. were isolated from the rhizosphere of potato plants (Algeria) by serial dilutions of rhizosphere soils on Kings B medium and were tested for their antifungal activity. The antifungal activity of the Pseudomonas isolated from Potatoes rhizosphere was tested against Pythium ultimum, Rhizoctonia solani and Fusarium oxysporum in dual culture with bacteria on PDA. The Petri dish was divided into tow, on one the bacteria was spread and on the opposite side fungal plugs were inoculated and incubated for one week. Fourteen bacteria were isolated; only one isolate inhibited the growth of Pythium ultimum, Rhizoctonia solani, Fusarium solani; Fusarium oxysporum f.sp. albedinis and Fusarium oxysporum f. sp. Lycopersici with inhibition zones of 39.9, 33.7, 30.8, 19.9 and 22.5 mm respectively. PMID:21534477

Mezaache, S; Guechi, A; Zerroug, M M; Strange, R N; Nicklin, J

2010-01-01

147

A Prototype Antifungal Contact Lens  

PubMed Central

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.

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

2011-01-01

148

Clinical efficacy of echinocandin antifungals.  

PubMed

The prevalence of fungal infections has increased significantly over the past few decades. Candida and Aspergillus spp. are the most common fungal pathogens due to recent changes in medical technology. Amphotericin B continues to be the treatment of choice in many severe disseminated mycosis cases, but problems with toxicity, resistance and non-availability of an absorbable oral form are important drawbacks. The azoles offer a less toxic alternative but often they are not as effective as amphotericin B and resistance is an increasing problem. The echinocandins are new active antifungal agents with a novel mechanism of action. During the past year, one agent has been released and two others are undergoing advanced stages of investigation. Although these agents are not the ideal antifungal drug, they do offer new options of therapy. PMID:11964885

Arathoon, E G

2001-12-01

149

Antifungal Susceptibility Tests of Aspergillus Species  

Microsoft Academic Search

\\u000a Although different methods are now available to assess the susceptibility of Aspergillus species to antifungal agents, there are still limited data correlating in vitro resistance with meaningful clinical endpoints.\\u000a Moreover, there is no consensus on the breakpoints to define resistance\\/susceptibility to different antifungal agents. This\\u000a chapter reviews the technical issues related to antifungal susceptibility tests for Aspergillus species, including the

Arnaldo Lopes Colombo; Viviane Reis; Patricio Godoy

150

Antifungal Resistance Mechanisms in Dermatophytes  

Microsoft Academic Search

Although fungi do not cause outbreaks or pandemics, the incidence of severe systemic fungal infections has increased significantly,\\u000a mainly because of the explosive growth in the number of patients with compromised immune system. Thus, drug resistance in\\u000a pathogenic fungi, including dermatophytes, is gaining importance. The molecular aspects involved in the resistance of dermatophytes\\u000a to marketed antifungals and other cytotoxic drugs,

Nilce M. Martinez-Rossi; Nalu T. A. Peres; Antonio Rossi

2008-01-01

151

Antifungal Susceptibility Testing and Therapy  

Microsoft Academic Search

\\u000a The development of new therapies to treat fatal diseases is creating an increasing number of patients who have predisposing\\u000a factors for infections by opportunistic yeasts. The rise in the prevalence of fungal infections has been the drive to develop\\u000a and license several new antifungal agents such as new formulations of polyenes, new triazole agents and echinocandins. The\\u000a availability of distinct

Manuel Cuenca-Estrella; Juan Luis Rodriguez-Tudela

152

Defensins: antifungal lessons from eukaryotes  

PubMed Central

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.

Silva, Patricia M.; Goncalves, Sonia; Santos, Nuno C.

2014-01-01

153

Development of Prophylactic Anti-Fungal Preparations.  

National Technical Information Service (NTIS)

In order to develop better topical anti-fungal agents with prophylactic activity against common ringworm infection a chemical assay for sodium pyrithione (a known anti-fungal drug) was developed in stratum corneum and its persistence there determined a do...

S. Riegelman W. L. Epstein R. A. Upton

1980-01-01

154

Screening antifungal activities of selected medicinal plants  

Microsoft Academic Search

Plants synthesise a vast array of secondary metabolites that are gaining importance for their biotechnological applications. The antifungal activity of the ethanolic extracts of ten Argentinean plants used in native medicine is reported. Antifungal assays included radial growth inhibition, disk and well diffusion assays and growth inhibition by broth dilution tests. The chosen test fungi were yeasts, microfungi and wood-rot

Emma Nelly Quiroga; Antonio Rodolfo Sampietro; Marta Amelia Vattuone

2001-01-01

155

Well diffusion for antifungal susceptibility testing  

Microsoft Academic Search

Introduction: The increasing clinical and microbiologic resistance of Candida spp. isolates to several antifungal agents is becoming a serious problem. It is now reasonable to propose the use of antifungal susceptibility testing in Candida spp. isolates from patients who have failed conventional therapy, before the selection of an empirical therapy.Methods: One hundred and fifty eight isolates of Candida spp. were

S Magaldi; S Mata-Essayag; C Hartung de Capriles; C Perez; M. T Colella; Carolina Olaizola; Yudith Ontiveros

2004-01-01

156

Antifungal Activity of C-27 Steroidal Saponins  

PubMed Central

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.

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

2006-01-01

157

Antifungal stilbenoids from Stemona collinsae.  

PubMed

Fifteen new stilbenoids including 11 phenylbenzofurans, the stemofurans A-K (1-11), and four dihydrostilbenes, the stilbostemins A (15), C (17), E (19), and F (20), were isolated and identified from a methanolic extract of Stemona collinsae roots together with five known derivatives, the stilbenes pinosylvin (13) and 4'-methylpinosylvin (14), the dihydrostilbenes, stilbostemins B (16) and D (18), and the dihydrophenanthrene racemosol (12) as well as (+)-sesamin, coniferyl alcohol, and stigmasterol. Bioautographic tests with Cladosporium herbarum displayed antifungal activity for stilbenoids of all four structural types. Ten derivatives were tested against five microfungi using the microdilution technique linked with digital image analysis of germ tubes. PMID:12088422

Pacher, T; Seger, C; Engelmeier, D; Vajrodaya, S; Hofer, O; Greger, H

2002-06-01

158

Current concepts in antifungal susceptibility testing, part I  

Microsoft Academic Search

A variety of antifungal agents are available to treat serious fungal infections, and a number of antifungal agents are under development. With the increasing prevalence of mycotic infections, particularly in immunosuppressed patients, and with the emergence of drug resistance to these agents, there is an increased need to perform antifungal susceptibility testing to determine which of the available antifungal agents

Robert S. Liao; W. Michael Dunne

2003-01-01

159

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...

160

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...

161

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 ...

162

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 ...

163

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 ...

164

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-...

165

COMPARISON OF HEPATIC GENE EXPRESSION PROFILES FROM MICE EXPOSED TO THREE TOXICOLOGICALLY DIFFERENT CONAZOLES  

EPA Science Inventory

Conazoles comprise a chemical class of fungicides used as agricultural and pham-taceutical products. Both propiconazole and triadimefon are hepatotoxic and hepatotumorigenic in mice, while myclobutanil is not a mouse liver tumorigen. The tumorigenic activities of these conazoles ...

166

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...

167

Direct application of carbendazim and propiconazole at field rates to the external mycelium of three arbuscular mycorrhizal fungi species: effect on 32 P transport and succinate dehydrogenase activity  

Microsoft Academic Search

The influence of the systemic fungicides propiconazole (Tilt 250E) and carbendazim (Bavistin) at field application rates\\u000a on the functioning of three arbuscular mycorrhizal fungi was studied. Short-term fungal 32P transport and succinate dehydrogenase (SDH) activity in external hyphae of Glomus intraradices Schenck and Smith, G. claroideum Schenck and Smith and G. invermaium Hall in symbiosis with pea (Pisum sativum L.)

Monica Kling; Iver Jakobsen

1997-01-01

168

Side effects of propiconazole (tilt 250 EC TM ) on non-target soil fungi in a field trial compared with natural stress effects  

Microsoft Academic Search

The present study was performed as a dose-response field experiment using a trade marked formulation of the ergosterol biosynthesis\\u000a inhibiting fungicide, propiconazole, applied at the recommended and ten times the recommended application rates. The soil\\u000a dilution plate method was used to isolate fungi from 0–1 and 1–2 cm soil depth. Soil samples were taken 10 times during the\\u000a period from

Susanne Elmholt

1991-01-01

169

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

Microsoft Academic Search

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?g\\/l) for 7,

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

2010-01-01

170

Antifungal peptides homologous to the Penicillium chrysogenum antifungal protein (PAF) are widespread among Fusaria.  

PubMed

Putative antifungal peptide encoding genes containing Penicillium chrysogenum antifungal protein (PAF) characteristic amino acid motifs were identified in 15 Fusarium isolates, representing 10 species. Based on the predicted sequences of mature peptides, discrepancy in one, two or three amino acids was observed between them. Phylogenetic investigations revealed that they show high amino acid sequence similarity to PAF and they belong to the group of fungal derived antifungal peptides with PAF-cluster. Ten from the 15 partially purified <10 kDa peptide fraction of Fusarium ferment broths showed antifungal activity. The presence of approximately 6.3 kDa molecular weight peptides was detected in all of the antifungally active ferment broths, and this peptide was isolated and purified from Fusarium polyphilaidicum. The minimal inhibitiory concentrations of F. polyphilaidicum antifungal protein (FPAP) were determined against different filamentous fungi, yeasts and bacteria. Filamentous fungal species were the most susceptible to FPAF, but some yeasts were also slightly sensitive. PMID:23174348

Galgóczy, László; Virágh, Máté; Kovács, Laura; Tóth, Beáta; Papp, Tamás; Vágvölgyi, Csaba

2013-01-01

171

Antifungal Drug Resistance: Clinical Relevance and Impact of Antifungal Drug Use  

Microsoft Academic Search

Antifungal drug resistance significantly impacts treatment outcomes in patients with invasive fungal infections (IFIs). Although\\u000a primary (intrinsic) resistance may occur independent of previous therapy, prior concomitant antifungal exposure increases\\u000a the risk for secondary (acquired) resistance and subsequent colonization or infection with less-susceptible pathogens. Among\\u000a various pathogen-antifungal combinations, this effect has been best studied clinically with azole exposure and the risk

Richard H. Drew; Mary L. Townsend

2010-01-01

172

Antifungal proteins: More than antimicrobials?  

PubMed Central

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.

Hegedus, Nikoletta; Marx, Florentine

2013-01-01

173

The Triphenylethylenes, a Novel Class of Antifungals  

PubMed Central

ABSTRACT New antifungals are needed, particularly in the developing world, to treat life-threatening fungal infections, such as cryptococcosis. Drug repurposing is one strategy to identify new drug-like compounds, but it is often difficult to identify a mechanism of action. Here we discuss the outstanding effort by Butts et al. to identify calmodulin as an antifungal target of repurposed estrogen receptor antagonists [A. Butts, K. Koselny, Y. Chabrier-Roselló, C. P. Semighini, Y. C. S. Brown, et al., mBio 5(1):e00765-13, 2014, doi:10.1128/mBio.00765-13]. The authors show that these compounds bind to and directly inhibit fungal calmodulin and also reduce fungal burden in an animal disease model. These studies thus establish both the key preclinical efficacy and the antifungal mechanism of action, which will allow these compounds to progress toward development of novel antifungal therapies.

2014-01-01

174

Antifungal susceptibility of Malassezia pachydermatis biofilm.  

PubMed

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

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

2013-11-01

175

Rechargeable Infection-responsive Antifungal Denture Materials  

Microsoft Academic Search

Candida-associated denture stomatitis (CADS) is a significant clinical concern. We developed rechargeable infection-responsive antifungal denture materials for potentially managing the disease. Polymethacrylic acid (PMAA) was covalently bound onto diurethane dimethacrylate denture resins in the curing step. The PMAA resins bound cationic antifungal drugs such as miconazole and chlorhexidine digluconate (CG) through ionic interactions. The anticandidal activities of the drug-containing PMAA-resin

Z. Cao; X. Sun; C.-K. Yeh; Y. Sun

2010-01-01

176

Antifungal stewardship in invasive Candida infections.  

PubMed

Bloodstream and other invasive infections due to Candida species (invasive fungal diseases = IFD) are a major cause of morbidity and mortality in hospitalized adults and children in many countries worldwide. The high infection-related morbidity and mortality associated with invasive Candida infection/candidaemia (IC/C), combined with suboptimal diagnostic tools, have driven the overuse of antifungal drugs. Antifungal stewardship (AFS) may be regarded as subentity of the more general term Anti-infective or Antimicrobial Stewardship Program (AIS/AMS). The high costs and high contribution of antifungal agents to the management of IFDs along with their recognized toxicities have been addressed as the principal justification for antifungal stewardship. AFS programmes should be organized by an interdisciplinary team of clinicians, pharmacists, microbiologists and infection control experts with the lead of an infectious disease specialist preferably in each large hospital/institution dealing with high-risk patients for invasive fungal infections. These programmes should consider various aspects of IC/C including (i) the local fungal epidemiology, (ii) information on antifungal resistance rates, (iii) establishing and application of therapeutic guidelines, (iv) implementation of treatment strategies for empirical, pre-emptive therapy including PK/PD data for antifungal drugs, de-escalation and 'switch and step-down strategies' (from intravenous to oral medication) in defined patient populations, (v) catheter management together with the application of routine diagnostic procedures such as ophthalmological and cardiac evaluations and (vi) the best available diagnostic tests for diagnosing IC and candidaemia. PMID:24661820

Ruhnke, M

2014-06-01

177

Antifungal activity of five species of Polygala  

PubMed Central

Crude extracts and fractions of five species of Polygala – P. campestris, P. cyparissias, P. paniculata, P. pulchella and P. sabulosa – were investigated for their in vitro antifungal activity against opportunistic Candida species, Cryptococcus gattii and Sporothrix schenckii with bioautographic and microdilution assays. In the bioautographic assays, the major extracts were active against the fungi tested. In the minimal concentration inhibitory (MIC) assay, the hexane extract of P. paniculata and EtOAc fraction of P. sabulosa showed the best antifungal activity, with MIC values of 60 and 30 ?g/mL, respectively, against C. tropicalis, C. gattii and S. schenckii. The compounds isolated from P. sabulosa prenyloxycoumarin and 1,2,3,4,5,6-hexanehexol displayed antifungal activity against S. schenckii (with MICs of 125 ?g/mL and 250 ?g/mL, respectively) and C. gattii (both with MICs of 250 ?g/mL). Rutin and aurapten isolated from P. paniculata showed antifungal activity against C. gattii with MIC values of 60 and 250 ?g/mL, respectively. In the antifungal screening, few of the isolated compounds showed good antifungal inhibition. The compound ?-spinasterol showed broad activity against the species tested, while rutin had the best activity with the lowest MIC values for the microorganisms tested. These two compounds may be chemically modified by the introduction of a substitute group that would alter several physico-chemical properties of the molecule, such as hydrophobicity, electronic density and steric strain.

Johann, Susana; Mendes, Beatriz G.; Missau, Fabiana C.; de Resende, Maria A.; Pizzolatti, Moacir G.

2011-01-01

178

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

PubMed

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 ?g 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. PMID:21190711

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

2011-04-01

179

Ultrashort antibacterial and antifungal lipopeptides  

PubMed Central

Host-defense cationic antimicrobial peptides (?12–50 aa long) play an essential protective role in the innate immune system of all organisms. Lipopeptides, however, are produced only in bacteria and fungi during cultivation, and they are composed of specific lipophilic moieties attached to anionic peptides (six to seven amino acids). Here we report the following. (i) The attachment of an aliphatic chain to otherwise inert, cationic D,L tetrapeptides endows them with potent activity against various microorganisms including antibiotic resistance strains. (ii) Cell specificity is determined by the sequence of the short peptidic chain and the length of the aliphatic moiety. (iii) Despite the fact that the peptidic chains are very short, their mode of action involves permeation and disintegration of membranes, similar to that of many long antimicrobial peptides. Besides adding important information on the parameters necessary for host-defense lipopeptides to kill microorganisms, the simple composition of these lipopeptides and their diverse specificities should make them economically available, innate immunity-mimicking antimicrobial and antifungal compounds for various applications.

Makovitzki, Arik; Avrahami, Dorit; Shai, Yechiel

2006-01-01

180

Posaconazole: a new antifungal weapon.  

PubMed

The last twenty years, the incidence of invasive fungal infections (IFI) has risen dramatically due to the prolongation of survival of patients with multiple risk factors for fungal infections. Amphotericin B was for more than 40 years the gold standard for almost all IFI, but toxicity and resistance, especially of new and emerging pathogens remained important issues. Fluconazole and itraconazole have also the same disadvantage of resistance. Voriconazole, a new triazole antifungal has offered an additional option, but the problem of resistant aspergillosis, and zygomycosis remains. Echinocandins (caspofungin, micafungin and anidulafungin) are active only against Candida and Aspergillus spp., but not against Fusarium, Scedosporium and Zygomycetes. Posaconazole is the most recently approved triazole with broad spectrum activity against Candida spp., Aspergillus spp., Cryptococcus neoformans, Zygomycetes, dermatiaceous, dimorphic, and other fungal pathogens. Interestingly, posaconazole is active against Candida spp., resistant to fluconazole and itraconazole, and Aspergillus fumigatus resistant to fluconazole itraconazole, amphotericin B, and voriconazole. The results from clinical trials of posaconazole as salvage treatment are encouraging. Multicenter clinical trials have also established its role in the prophylaxis of (IFI) in the severely immunocompromised patients such as those after hematopoietic stem cell transplantation (HSCT) who developed graft versus host disease (GVHD), as well as the neutropenic patients with an acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after myeloablative chemotherapy. Posaconazole has pharmacokinetic advantages and low side effect profile, which are very important, especially in the seriously ill population. PMID:21682687

Aperis, Georgios; Alivanis, Polichronis

2011-09-01

181

21 CFR 333.210 - Antifungal active ingredients.  

Code of Federal Regulations, 2013 CFR

...Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Topical Antifungal Drug Products § 333.210 Antifungal active...

2013-04-01

182

ASDCD: antifungal synergistic drug combination database.  

PubMed

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. PMID:24475134

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

2014-01-01

183

ASDCD: Antifungal Synergistic Drug Combination Database  

PubMed Central

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.

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

2014-01-01

184

Antifungal susceptibility testing of yeasts: uses and limitations  

Microsoft Academic Search

With recent developments in the field of mycology, such as increased incidence of fungal infections, the introduction of newer, safer antifungals, and the emergence of resistance, the need for clinically relevant antifungal susceptibility testing methods is obvious. Studies performed over the past decade have allowed the National Committee for Clinical Laboratory Standards Subcommittee on Antifungal Testing to achieve consensus on

Guadalupe Reyes; Mahmoud A. Ghannoum

2000-01-01

185

Synthesis of new antifungal peptides selective against Cryptococcus neoformans  

Microsoft Academic Search

Many drugs are available for the treatment of systemic or superficial mycoses, but only a limited number of them are effective antifungal drugs, devoid of toxic and undesirable side effects. Furthermore, resistance development and fungistatic rather than fungicidal activities represent limitations of current antifungal therapy. Therefore there remains an urgent need for a new generation of antifungal agents.According to a

Manuela Grimaldi; Margherita De Rosa; Sara Di Marino; Mario Scrima; Brunella Posteraro; Maurizio Sanguinetti; Giovanni Fadda; Annunziata Soriente; Anna Maria D’Ursi

2010-01-01

186

Plant and Bacterial Chitinases Differ in Antifungal Activity  

Microsoft Academic Search

Chitinases were isolated from the grains of wheat, barley and maize, and compared with those obtained from Serratia marcescens, Streptomyces griseus and Pseudomonas stutzeri for antifungal activity and enzyme specificity. The six enzymes were tested for antifungal activity using an assay based upon inhibition of hyphal extension of the fungi Trichoderma reesei and Phycomyces blakesleeanus. Antifungal activity was observed with

WALDEN K. ROBERTS; CLAUDE P. SELITRENNIKOFF

1988-01-01

187

Pharmacodynamic implications for use of antifungal agents.  

PubMed

In the last decade, the relationship between drug dosing and treatment efficacy for life-threatening fungal infections has been clarified by application of pharmacodynamic principles to the study of antifungal agents. Similar to antibacterials, antifungal agents can display static or cidal patterns of activity against pathogenic fungi that can be broadly classified as either concentration-dependent or concentration-independent. The differences between these pharmacodynamic patterns can play an important role in the selection and dosing of antifungal therapy, especially in the treatment of uncommon or resistant mycoses. Knowledge of these pharmacodynamic characteristics may also guide an exploration of unconventional dosing strategies that could prove to be as effective, safe, and more convenient in critically ill or persistently immunosuppressed patients. PMID:17616480

Lewis, Russell E

2007-10-01

188

Epidemiology and antifungal resistance in invasive candidiasis  

PubMed Central

The epidemiology of Candida infections has changed over the last two decades: The number of patients suffering from such infections has increased dramatically and the Candida species involved have become more numerous as Candida albicans is replaced as an infecting agent by various non-C. albicans species (NAC). At the same time, additional antifungal agents have become available. The different Candida species may vary in their susceptibility for these various antifungals. This draws more attention to in vitro susceptibility testing. Unfortunately, several different test methods exist that may deliver different results. Moreover, clinical breakpoints (CBP) that classify test results into susceptible, intermediate and resistant are controver- sial between CLSI and EUCAST. Therefore, clinicians should be aware that interpretations may vary with the test system being followed by the microbiological laboratory. Thus, knowledge of actual MIC values and pharmacokinetic properties of individual antifungal agents is important in delivering appropriate therapy to patients

2011-01-01

189

Antifungal drug discovery: the process and outcomes.  

PubMed

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

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

2014-06-01

190

New Antifungal Pyranoisoflavone from Ficus tikoua Bur.  

PubMed Central

Considering the undesirable attributes of synthetic fungicides and the availability of Ficus species in China, the stem of Ficus tikoua Bur. was investigated. One new antifungal pyranoisoflavone, 5,3?,4?-trihydroxy-2?,2?-dimethylpyrano (5?,6?:7,8) isoflavone (1), together with two known isoflavones, wighteone (2) and lupiwighteone (3) (with previously reported antifungal activities), were isolated from ethyl acetate extract by bioassay-guided fractionation. Their structures were determined by spectroscopic analysis, such as NMR (1H-1H COSY, HMQC, HMBC and NOESY), IR, UV and HRMS, as well as ESI-MSn analyses. The antifungal activities of 1–3 against Phytophthora infestans were evaluated by direct spore germination assay, and the IC50 values were 262.442, 198.153 and 90.365 ?g·mL?1, respectively.

Wei, Shaopeng; Wu, Wenjun; Ji, Zhiqin

2012-01-01

191

Rechargeable Infection-responsive Antifungal Denture Materials  

PubMed Central

Candida-associated denture stomatitis (CADS) is a significant clinical concern. We developed rechargeable infection-responsive antifungal denture materials for potentially managing the disease. Polymethacrylic acid (PMAA) was covalently bound onto diurethane dimethacrylate denture resins in the curing step. The PMAA resins bound cationic antifungal drugs such as miconazole and chlorhexidine digluconate (CG) through ionic interactions. The anticandidal activities of the drug-containing PMAA-resin discs were sustained for a prolonged period of time (weeks and months). Drug release was much faster at acidic conditions (pH 5) than at pH 7. Drugs bound to the denture materials could be “washed out” by treatment with EDTA, and the drug-depleted resins could be recharged with the same or a different class of anticandidal drugs. These results suggest clinical potential of the newly developed antifungal denture materials in the management of CADS and other infectious conditions.

Cao, Z.; Sun, X.; Yeh, C.-K.; Sun, Y.

2010-01-01

192

Rechargeable infection-responsive antifungal denture materials.  

PubMed

Candida-associated denture stomatitis (CADS) is a significant clinical concern. We developed rechargeable infection-responsive antifungal denture materials for potentially managing the disease. Polymethacrylic acid (PMAA) was covalently bound onto diurethane dimethacrylate denture resins in the curing step. The PMAA resins bound cationic antifungal drugs such as miconazole and chlorhexidine digluconate (CG) through ionic interactions. The anticandidal activities of the drug-containing PMAA-resin discs were sustained for a prolonged period of time (weeks and months). Drug release was much faster at acidic conditions (pH 5) than at pH 7. Drugs bound to the denture materials could be "washed out" by treatment with EDTA, and the drug-depleted resins could be recharged with the same or a different class of anticandidal drugs. These results suggest clinical potential of the newly developed antifungal denture materials in the management of CADS and other infectious conditions. PMID:20940361

Cao, Z; Sun, X; Yeh, C-K; Sun, Y

2010-12-01

193

Antifungal medications or disinfectants for denture stomatitis.  

PubMed

Data sourcesThe Cochrane database of systematic reviews, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase databases and reference lists of identified articles were searched with no language restriction.Study selectionRandomised controlled trials that compared the efficacy of antifungal medications with other treatments of denture-related erythematous stomatitis in adults wearing conventional acrylic removable complete dentures were included. Trials of seven days or fewer were excluded.Data extraction and synthesisStudy assessment and data extraction were carried out independently by at least two reviewers. Study quality was assessed using Cochrane methodology. Odds Ratios (OR) and 95% Confidence Interval (CI) were calculated to compare results across studies using a random effects model.ResultsFourteen randomised controlled trials were included in the review, with eight studies contributing to the meta-analysis. No statistically significant difference between antifungal treatment and disinfection methods was found for both clinical and microbiological outcomes. Meta-analysis showed a statistically significant difference between an antifungal and a placebo for the microbiological outcome (OR=0.32; 95% CI: 0.12-0.89; Z=-2.2; p=0.028), favouring the antifungals. There was no statistically significant difference between antifungal and placebo for the clinical outcome (OR=0.2; 95% CI: 0.04-1.04; Z=-1.9; p=0.056).ConclusionsThe findings of this review and meta-analysis suggest that disinfection methods could be considered as an adjunct or alternative to antifungal medications in the treatment of denture stomatitis. PMID:24971864

Lalla, Rajesh V; Dongari-Bagtzoglou, Anna

2014-06-01

194

Potato Dextrose Agar Antifungal Susceptibility Testing for Yeasts and Molds: Evaluation of Phosphate Effect on Antifungal Activity of CMT3  

Microsoft Academic Search

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.

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

2002-01-01

195

Antimycobacterial and antifungal isosters of salicylamides.  

PubMed

A set of 40 derivatives of 3-hydroxypicolinic acid and 2-sulfanylbenzoic acid, isosteric to salicylanilides was synthesized. The compounds were evaluated for in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium, Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon beigelii, Aspergillus fumigatus, Absidia corymbifera, Trichophyton mentagrophytes and Microsporum gypseum. Structure-activity relationships of antimycobacterial activity and antifungal activity against T. mentagrophytes and M. gypseum were analyzed by the Free-Wilson method. An increase in antimycobacterial activity was observed only for the sulfanylbenzoic acid derivatives, especially those with the benzyl moiety. The antifungal activity was not significant. PMID:12953220

Waisser, Karel; Pesina, Milan; Holý, Pavel; Pour, Milan; Bures, Otakar; Kunes, Jisí; Klimesová, Vsra; Buchta, Vladimír; Kubanová, Petra; Kaustová, Jarmila

2003-08-01

196

Screening antifungal activities of selected medicinal plants.  

PubMed

Plants synthesise a vast array of secondary metabolites that are gaining importance for their biotechnological applications. The antifungal activity of the ethanolic extracts of ten Argentinean plants used in native medicine is reported. Antifungal assays included radial growth inhibition, disk and well diffusion assays and growth inhibition by broth dilution tests. The chosen test fungi were yeasts, microfungi and wood-rot causing Basidiomycetes. Extracts of Larrea divaricata, Zuccagnia punctata and Larrea cuneifolia displayed remarkable activity in the assays against the majority of the test fungi. In addition to the former plants, Prosopanche americana also inhibited yeast growth. PMID:11137353

Quiroga, E N; Sampietro, A R; Vattuone, M A

2001-01-01

197

Borrelidin, a potent antifungal agent: insight into the antifungal mechanism against Phytophthora sojae.  

PubMed

Borrelidin has high and specific antifungal activity against Phytophthora sojae . To explore the antifungal mechanism of borrelidin against P. sojae , the relationship between the antifungal activity of borrelidin and the concentration of threonine was evaluated. The results demonstrated that the growth-inhibitory effect of borrelidin on the growth of P. sojae was antagonized by threonine in a dose-dependent manner, suggesting that threonyl-tRNA synthetase (ThrRS) may be the potential target of borrelidin. Subsequently, the inhibition of the enzymatic activity of ThrRS by borrelidin in vitro was confirmed. Furthermore, the detailed interaction between ThrRS and borrelidin was investigated using fluorescence spectroscopy and circular dichroism (CD), implying a tight binding of borrelidin to ThrRS. Taken together, these results suggest that the antifungal activity of borrelidin against P. sojae was mediated by inhibition of ThrRS via the formation of the ThrRS-borrelidin complex. PMID:22967236

Gao, Ya-Mei; Wang, Xiang-Jing; Zhang, Ji; Li, Ming; Liu, Chong-Xi; An, Jing; Jiang, Ling; Xiang, Wen-Sheng

2012-10-01

198

Synthetic multivalent antifungal peptides effective against fungi.  

PubMed

Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. B4010 displayed better antifungal properties than natamycin and amphotericin B. The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes. S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. The studies further suggested that the first arginine is important for mediating peptide-bilayer interactions. Replacing the first arginine led to a 2-4 fold decrease in antifungal activities and reduced membrane disruption properties. The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides. PMID:24498363

Lakshminarayanan, Rajamani; Liu, Shouping; Li, Jianguo; Nandhakumar, Muruganantham; Aung, Thet Tun; Goh, Eunice; Chang, Jamie Ya Ting; Saraswathi, Padhmanaban; Tang, Charles; Safie, Siti Radiah Binte; Lin, Lim Yih; Riezman, Howard; Lei, Zhou; Verma, Chandra S; Beuerman, Roger W

2014-01-01

199

Antifungal activity of Cynara scolymus L. extracts  

Microsoft Academic Search

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.

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

2005-01-01

200

Antifungal potential of Indian medicinal plants  

Microsoft Academic Search

Fourteen Indian plants, selected based on their use in respiratory and other disorders in traditional systems of medicine, were analyzed for their potential activity against fungi. The antifungal activity was investigated by disc diffusion, microbroth dilution and percent spore germination inhibition tests against pathogenic Aspergilli. Methanolic extracts of Solanum xanthocarpum and Datura metel inhibited the growth of Aspergillus fumigatus, A.

Rajesh Dabur; H. Singh; A. K. Chhillar; M. Ali; G. L. Sharma

2004-01-01

201

Antifungal Susceptibility Testing: Current Role from the Clinical Laboratory Perspective  

PubMed Central

Despite availability of many antifungal agents, antifungal clinical resistance occurs, perhaps as a consequence of an infecting organism found to be resistant in vitro to one or more antifungals tested. From what derives the important current role of the in vitro antifungal susceptibility testing (AFST), that is to determine which agents are like to be scarcely effective for a given infection. Thus, AFST results, if timely generated by the clinical microbiology laboratory and communicated to clinicians, can aid them in the therapeutic decision making, especially for difficult-to-treat invasive candidiasis and aspergillosis. Although recently refined AFST methods are commercially available for allowing a close antifungal resistance surveillance in many clinical setting, novel assays such as flow cytometry or MALDI-TOF mass spectrometry are upcoming tools for AFST. Based on short-time antifungal drug exposure of fungal isolates, these assays could provide a reliable means for quicker and sensitive assessment of AFST.

Posteraro, Brunella; Torelli, Riccardo; De Carolis, Elena; Posteraro, Patrizia; Sanguinetti, Maurizio

2014-01-01

202

Antifungal susceptibility testing: current role from the clinical laboratory perspective.  

PubMed

Despite availability of many antifungal agents, antifungal clinical resistance occurs, perhaps as a consequence of an infecting organism found to be resistant in vitro to one or more antifungals tested. From what derives the important current role of the in vitro antifungal susceptibility testing (AFST), that is to determine which agents are like to be scarcely effective for a given infection. Thus, AFST results, if timely generated by the clinical microbiology laboratory and communicated to clinicians, can aid them in the therapeutic decision making, especially for difficult-to-treat invasive candidiasis and aspergillosis. Although recently refined AFST methods are commercially available for allowing a close antifungal resistance surveillance in many clinical setting, novel assays such as flow cytometry or MALDI-TOF mass spectrometry are upcoming tools for AFST. Based on short-time antifungal drug exposure of fungal isolates, these assays could provide a reliable means for quicker and sensitive assessment of AFST. PMID:24804003

Posteraro, Brunella; Torelli, Riccardo; De Carolis, Elena; Posteraro, Patrizia; Sanguinetti, Maurizio

2014-01-01

203

Synthesis of new antifungal peptides selective against Cryptococcus neoformans.  

PubMed

Many drugs are available for the treatment of systemic or superficial mycoses, but only a limited number of them are effective antifungal drugs, devoid of toxic and undesirable side effects. Furthermore, resistance development and fungistatic rather than fungicidal activities represent limitations of current antifungal therapy. Therefore there remains an urgent need for a new generation of antifungal agents. According to a polypharmacological approach, the present work concerns the synthesis and antifungal activity of a set of peptides designed to simultaneously target the fungal cell surface and lanosterol demethylase, a key enzyme involved in ergosterol synthesis. Our peptides include amino acid sequences characteristic of membrane-active antimicrobial peptides (AMP), and due to the presence of His residues, they carry the imidazole ring characteristic of azole compounds. The peptides synthesized by us, were tested against different yeast species, and displayed general antifungal activity, with a therapeutically promising antifungal specificity against Cryptococcus neoformans. PMID:20943406

Grimaldi, Manuela; De Rosa, Margherita; Di Marino, Sara; Scrima, Mario; Posteraro, Brunella; Sanguinetti, Maurizio; Fadda, Giovanni; Soriente, Annunziata; D'Ursi, Anna Maria

2010-11-15

204

Azole antifungal agents: emphasis on new triazoles.  

PubMed Central

Many advances have been made in antifungal therapy over the last three decades. Itraconazole and fluconazole, two investigational triazole agents, are the most recent additions to the list of antifungal drugs. This review has focused primarily on their mechanisms of action, favorable pharmacologic properties, and spectra of activity against a broad range of systemic pathogens. Itraconazole and fluconazole show much promise as orally active agents, with less potential for toxicity than the currently available azoles. Fluconazole and, to a lesser degree, itraconazole are especially promising therapies for cryptococcal meningitis. In addition, fluconazole may prove to be highly effective in urinary tract infections caused by Candida species and other fungi. Ongoing and future clinical trials will more clearly define the specific roles of itraconazole and fluconazole in the treatment of systemic mycoses.

Saag, M S; Dismukes, W E

1988-01-01

205

A new antifungal coumarin from Clausena excavata.  

PubMed

A new ?-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

Kumar, Ramashish; Saha, Aniruddha; Saha, Dipanwita

2012-01-01

206

Antifungal activity of 10 Guadeloupean plants.  

PubMed

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

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

207

Aspergillus--classification and antifungal susceptibilities.  

PubMed

Aspergillus is one of the most important fungal genera for the man, for its industrial use, its ability to spoil food and not least its medical impact as cause of a variety of diseases. Currently hundreds of species of Aspergillus are known; nearly fifty of them are able to cause infections in humans and animals. Recently, the genus Aspergillus is subdivided into 8 subgenera and 22 sections. The spectrum of diseases caused by Aspergillus species varies from superficial cutaneous to invasive and systemic infections. All species of Aspergillus investigated so far are resistant against the antifungals fluconazole and 5-fluorocytosine, the range of susceptibilities to currently available antifungals is discussed in this paper. PMID:23278534

Buzina, Walter

2013-01-01

208

Natural Killer Cells and Antifungal Host Response  

PubMed Central

As a result of improved experimental methodologies and a better understanding of the immune system, there is increasing insight into the antifungal activity of natural killer (NK) cells. Murine and human NK cells are able to damage fungi of different genera and species in vitro, and they exert both direct and indirect antifungal activity through cytotoxic molecules such as perforin and through cytokines and interferons, respectively. On the other hand, recent data suggest that fungi exhibit immunosuppressive effects on NK cells. Whereas clear in vivo data are lacking in humans, the importance of NK cells in the host response against fungi has been demonstrated in animal models. Further knowledge of the interaction of NK cells with fungi might help to better understand the pathogenesis of invasive fungal infections and to improve treatment strategies.

Schmidt, Stanislaw; Zimmermann, Stefanie-Yvonne; Tramsen, Lars; Koehl, Ulrike

2013-01-01

209

Novel conformationally restricted triazole derivatives with potent antifungal activity  

Microsoft Academic Search

In continuation of our work on azole antifungal agents, a series of new conformationally restricted triazole derivatives possessing benzylpiperidin-4-yl methyl amino side chains were designed and synthesized. All the new azoles showed moderate to excellent in vitro antifungal activity against most of the tested pathogenic fungi. Several compounds (such as 12e, 12f, 12h and 12n) showed higher antifungal activity against

Wenya Wang; Shengzheng Wang; Yang Liu; Guoqiang Dong; Yongbing Cao; Zhenyuan Miao; Jianzhong Yao; Wannian Zhang; Chunquan Sheng

2010-01-01

210

Using Antifungal Pharmacodynamics to Improve Patient Outcomes  

Microsoft Academic Search

In vitro and in vivo studies of available and investigational antifungals have broadened our understanding of the pharmacodynamics\\u000a of these agents as well as the pharmacokinetic\\/pharmacodynamic characteristics that are associated with efficacy. These data\\u000a are increasingly being used as surrogate means to answer questions about dosing and administration of antimicrobial agents\\u000a in order to improve outcomes in patients with invasive

Nathan P. Wiederhold

2010-01-01

211

Current and Emerging Azole Antifungal Agents  

PubMed Central

Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging. This review describes present and future uses of the currently available azole antifungal agents in the treatment of systemic and superficial fungal infections and provides a brief overview of the current status of in vitro susceptibility testing and the growing problem of clinical resistance to the azoles. Use of the currently available azoles in combination with other antifungal agents with different mechanisms of action is likely to provide enhanced efficacy. Detailed information on some of the second-generation triazoles being developed to provide extended coverage of opportunistic, endemic, and emerging fungal pathogens, as well as those in which resistance to older agents is becoming problematic, is provided.

Sheehan, Daniel J.; Hitchcock, Christopher A.; Sibley, Carol M.

1999-01-01

212

Hydroxytyrosol expresses antifungal activity in vitro.  

PubMed

Hydroxytyrosol (HT) is a potent antioxidant found in olive oil and leaves. Using several in vitro approaches, we tested antifungal activity of HT. HT showed broad spectrum of antifungal activity against medically important yeasts and dermatophyte strains with MIC values ranging between 97.6 µgml?¹ and 6.25 mgml?¹. The antimicrobial activity of HT was also tested using the time-kill methodology. Below the MIC value, HT showed potent damage of cell wall of Candida albicans ATCC 10231 using fluorescent dye-exclusion method. At the subinhibitory concentration, HT also influenced dimorphic transition of Candida indicating that HT is inhibitor of germ-tube formation as one of the most important virulence factor of C. albicans. Furthermore, HT showed disturbances in cell surface hydrophobicity (CSH) of C. albicans. The in vitro results indicate that HT caused a significant cell wall damage and changes in CSH as well as inhibition of germ-tube formation as virulence factor of C. albicans. The study indicates that HT has a considerable in vitro antifungal activity against medically important yeasts. PMID:23721186

Zoric, Natasa; Horvat, Igor; Kopjar, Nevenka; Vucemilovic, Ante; Kremer, Dario; Tomic, Sinisa; Kosalec, Ivan

2013-08-01

213

Antifungal ellagitannin isolated from Euphorbia antisyphilitica Zucc  

PubMed Central

Objective To study antifungal activity of a new ellagitannin isolated from the plant residues of Euphorbia antisyphilitica (E. antisyphilitica) Zucc in the wax extraction process. Methods An extract was prepared from dehydrated and pulverized residues and fractionated by liquid chromatography on Amberilte XAD-16, until obtained an ellagitannin-rich ethanolic fraction which was treated by rotaevaporation to recover the ellagitannin as fine powder. An aqueous solution was prepared and treated through ionic exchange liquid chromatography (Q XL) and gel permeation chromatography (G 25). The ellagitannin-rich fraction was thermogravimetrically evaluated (TGA and DTA) to test the thermo-stability of ellagic acid (monomeric unit). Then ellagitannin powder was analyzed by infrared spectrospcopy to determinate the functional groups and, also mass spectroscopy was used to determine the molecular ion. Results The principal functional groups of ellagitannin were determined, the molecular weight was 860.7 g/mol; and an effective antifungal activity against phytopathogenic fungi was demonstrated. Conclusions It can be concluded that the new ellagitannin (860.7 g/mol) isolated from E. antisyphilitica Zucc is an effective antifungal agent against Alternaria alternata, Fusarium oxyzporum, Colletotrichum gloeosporoides and Rhizoctnia solani.

Ascacio-Valdes, Juan; Burboa, Edgardo; Aguilera-Carbo, Antonio F; Aparicio, Mario; Perez-Schmidt, Ramon; Rodriguez, Raul; Aguilar, Cristobal N

2013-01-01

214

Nonanoic Acid, an Antifungal Compound from Hibiscus syriacus Ggoma  

PubMed Central

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.

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

2012-01-01

215

Nonanoic Acid, an Antifungal Compound from Hibiscus syriacus Ggoma.  

PubMed

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

Jang, Yun-Woo; Jung, Jin-Young; Lee, In-Kyoung; Kang, Si-Yong; Yun, Bong-Sik

2012-06-01

216

Evaluation of solid sorbents for the determination of fenhexamid, metalaxyl-M, pyrimethanil, malathion and myclobutanil residues in air samples: application to monitoring malathion and fenhexamid dissipation in greenhouse air using C-18 or Supelpak-2 for sampling.  

PubMed

A methodology is described for greenhouse air analysis by sampling fenhexamid, pyrimethanil, malathion, metalaxyl-M and myclobutanil in solid sorbents. Pesticides were determined by gas chromatography with NP Detector. The trapping efficiency of XAD-2, XAD-4, Supelpak-2, Florisil and C-18 at different sampling conditions (rate, time and air humidity) and pesticides concentration levels has been evaluated. No breakthrough was observed in the range of concentration studied (0.10-75 microg of each pesticide). In almost all the cases good stability results were obtained. Personal pumps have been used with selected sorbents (Supelpak-2 and C-18) in order to sample malathion and fenhexamid in air of experimental greenhouse after their application in a tomato crop. The dissipation process of the analytes in various time periods after application has been studied. Malathion concentrations varied between 20.1 microg m(-3) just after application and 1.06 microg m(-3) 3 days later. Fenhexamid concentrations, determined by high performance liquid chromatography with UV detection, fall rapidly; after 12 h post-application being below 0.50 microg m(-3). PMID:17723526

Tsiropoulos, Nikolaos G; Bakeas, Evangelos B; Raptis, Vasilios; Batistatou, Stavroula S

2006-07-28

217

Impact of new antifungal breakpoints on antifungal resistance in Candida species.  

PubMed

We reviewed our antifungal susceptibility data for micafungin, anidulafungin, fluconazole, and voriconazole against Candida species and compared resistance rates determined by the previous and recently revised CLSI antifungal breakpoints. With the new breakpoints, resistance was significantly increased for micafungin (from 0.8% to 7.6%), anidulafungin (from 0.9% to 7.3%), and voriconazole (from 6.1% to 18.4%) against Candida glabrata. Resistance was also increased for fluconazole against Candida albicans (from 2.1% to 5.7%). PMID:24403302

Fothergill, Annette W; Sutton, Deanna A; McCarthy, Dora I; Wiederhold, Nathan P

2014-03-01

218

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

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.

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

2014-01-01

219

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

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

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

2014-07-01

220

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...

221

In vitro methods for antifungal susceptibility testing of Trichophyton spp  

Microsoft Academic Search

In general, methods to test the susceptibility of fungi to antifungal drugs require standardized techniques, but so far there is no methodology that is widely applicable to dermatophytes. Here we introduced modifications to the protocols from documents of the National Committee for Clinical Laboratory Standards (CLSI) M38-A and the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility

Maria Elisabete da Silva Barros; Daniel de Assis Santos; Júnia Soares Hamdan

2006-01-01

222

Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia  

Microsoft Academic Search

The efficacy of antifungal prophylaxis with itraconazole capsules and its serum concentrations were evaluated in patients intensively treated for acute leukaemia. A consecutive group of patients without systemic antifungal prophylaxis (January 1993 to August 1994, period 1) was compared with another consecutive group of patients (period 2) who received itraconazole capsules (September 1994 to April 1995 400 mg\\/day, from May

A Glasmacher; E Molitor; C Hahn; K Bomba; S Ewig; C Leutner; E Wardelmann; IGH Schmidt-Wolf; J Mezger; G Marklein; T Sauerbruch

1998-01-01

223

Antifungal activity of Piper diospyrifolium Kunth (Piperaceae) essential oil  

PubMed Central

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.

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

2011-01-01

224

Antifungal Chemical Compounds Identified Using a C. elegans Pathogenicity Assay  

Microsoft Academic Search

There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans

Julia Breger; Beth Burgwyn Fuchs; George Aperis; Terence I Moy; Frederick M Ausubel; Eleftherios Mylonakis

2007-01-01

225

Current concepts in antifungal susceptibility testing, Part II  

Microsoft Academic Search

Standardization of antifungal susceptibility testing methods for yeasts has been recently followed by the NCCLS M38-A standard broth microdilution method for testing some of the more common filamentous moulds that cause invasive disease. Part II of this article will address some of the issues and concerns surrounding the performance of antifungal susceptibility testing. Recommended guidelines will also be presented for

Robert S. Liao; W. Michael Dunne

2003-01-01

226

Antifungal susceptibility testing and drug interaction modeling in moulds  

Microsoft Academic Search

In this thesis two parameters of in vitro antifungal susceptibility testing of filamentous fungi, the medium and the quantification of fungal growth, were investigated and different drug interaction models were used for analyzing the in vitro combination of various antifungal drugs. A microbroth kinetic system was developed in order to analyze the growth curves of three species of filamentous fungi

Joseph Meletiadis

2002-01-01

227

Gene Expression and Evolution of Antifungal Drug Resistance  

Microsoft Academic Search

Permanent changes in gene expression result from certain forms of antifungal resistance. In this study, we asked whether any changes in gene expression are required for the evolution of a drug-resistant phenotype in populations. We examined the changes in gene expression resulting from the evolution of resistance in exper- imental populations of the yeast Saccharomyces cerevisiae with two antifungal drugs,

James B. Anderson; Caroline Sirjusingh; Nazia Syed; Shantelle Lafayette

2009-01-01

228

Synthesis of novel substituted tetrazoles having antifungal activity  

Microsoft Academic Search

In an effort to find potent antifungal agents, a variety of triazole derivatives with a 5-substituted tetrazole structure 6, 7, 12 and 14 were prepared and evaluated for antifungal activity against Candida spp., Cryptococcus neoformans, and Aspergillus spp. in vitro. The location of the methyl group at the C-3 of compounds 12 and 14 has been demonstrated to be a

Ram Shankar Upadhayaya; Sanjay Jain; Neelima Sinha; Nawal Kishore; Ramesh Chandra; Sudershan K Arora

2004-01-01

229

Antifungal and antiviral products of marine organisms.  

PubMed

Marine organisms including bacteria, fungi, algae, sponges, echinoderms, mollusks, and cephalochordates produce a variety of products with antifungal activity including bacterial chitinases, lipopeptides, and lactones; fungal (-)-sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride; algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone, bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (-)-ageloxime D, haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da antifungal peptide. The antiviral compounds from marine organisms include bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A, purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid, glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03, meroditerpenoids, methyl ester derivative of vatomaric acid, lectins, polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin; echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and; tilapia hepcidin 1-5 (TH 1-5), seabream SauMx1, SauMx2, and SauMx3, and orange-spotted grouper ?-defensin. Although the mechanisms of antifungal and antiviral activities of only some of the aforementioned compounds have been elucidated, the possibility to use those known to have distinctly different mechanisms, good bioavailability, and minimal toxicity in combination therapy remains to be investigated. It is also worthwhile to test the marine antimicrobials for possible synergism with existing drugs. The prospects of employing them in clinical practice are promising in view of the wealth of these compounds from marine organisms. The compounds may also be used in agriculture and the food industry. PMID:24562325

Cheung, Randy Chi Fai; Wong, Jack Ho; Pan, Wen Liang; Chan, Yau Sang; Yin, Cui Ming; Dan, Xiu Li; Wang, He Xiang; Fang, Evandro Fei; Lam, Sze Kwan; Ngai, Patrick Hung Kui; Xia, Li Xin; Liu, Fang; Ye, Xiu Yun; Zhang, Guo Qing; Liu, Qing Hong; Sha, Ou; Lin, Peng; Ki, Chan; Bekhit, Adnan A; Bekhit, Alaa El-Din; Wan, David Chi Cheong; Ye, Xiu Juan; Xia, Jiang; Ng, Tzi Bun

2014-04-01

230

Chemical modification of antifungal polyene macrolide antibiotics  

NASA Astrophysics Data System (ADS)

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.

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

2011-02-01

231

Nylon-3 Polymers with Selective Antifungal Activity  

PubMed Central

Host-defense peptides inhibit bacterial growth but show little toxicity toward mammalian cells. A variety of synthetic polymers have been reported to mimic this antibacterial selectivity; however, achieving comparable selectivity for fungi is more difficult because these pathogens are eukaryotes. Here, we report nylon-3 polymers based on a novel subunit that display potent antifungal activity (MIC = 3.1 ?g/mL for C. albicans) and favorable selectivity (IC10 > 400 ?g/mL for 3T3 fibroblast toxicity; HC10 > 400 ?g/mL for hemolysis).

Liu, Runhui; Chen, Xinyu; Hayouka, Zvika; Chakraborty, Saswata; Falk, Shaun P.; Weisblum, Bernard; Masters, Kristyn S.; Gellman, Samuel H.

2013-01-01

232

Antifungal ether diglycosides from Matayba guianensis Aublet.  

PubMed

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). PMID:24485783

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

233

Analogues of antifungal tjipanazoles from rebeccamycin.  

PubMed

Analogues of antifungal tjipanazoles were obtained by semi-synthesis from rebeccamycin, an antitumor antibiotic isolated from cultures of Saccharothrix aerocolonigenes. The antiproliferative activities of the new compounds were evaluated in vitro against nine tumor cell lines. The effect on the cell cycle of murine leukemia L1210 cells was examined and the antimicrobial activities against two Gram positive bacteria, a Gram negative bacterium and a yeast were determined. The inhibitory properties toward four kinases and toward topoisomerase I were evaluated. The most cytotoxic compound in the series was a dinitro derivative characterized as a potent topoisomerase I inhibitor. PMID:15051063

Voldoire, Aline; Moreau, Pascale; Sancelme, Martine; Matulova, Maria; Léonce, Stéphane; Pierré, Alain; Hickman, John; Pfeiffer, Bruno; Renard, Pierre; Dias, Nathalie; Bailly, Christian; Prudhomme, Michelle

2004-04-15

234

Antifungal activity of magnolol and honokiol  

Microsoft Academic Search

Two neolignan compounds, magnolol (5,5?-diallyl-2,2?-dihydroxybiphenyl,1) and honokiol (5,5?-diallyl-2,4?-dihydroxybiphenyl,2), were isolated from the stem bark ofMagnolia obovata and evaluated for antifungal activity against various human pathogenic fungi. Compound1 and2 showed significant inhibitory activities againstTrichophyton mentagrophytes, Microsporium gypseum, Epidermophyton floccosum, Aspergillus niger, Cryptococcus neoformans, andCandida albicans with minimum inhibitory concentrations (MIC) in a range of 25–100 ?g\\/ml. Therefore, compound1 and2 could be

Kyu Ho Bang; Yoon Kwan Kim; Byung Sun Min; Min Kyun Na; Young Ha Rhee; Jong Pill Lee; Ki Hwan Bae

2000-01-01

235

Synthesis and antifungal properties of papulacandin derivatives  

PubMed Central

Summary Derivatives of an antifungal agent that targets the ?-(1,3)-D-glucan synthase, papulacandin D, were synthesized and tested for activity. The papulacandin D structure contains a challenging benzannulated spiroketal unit, which is introduced in a palladium-catalyzed cross-coupling reaction of a glycal silanolate and an aryl iodide followed by an oxidative spiroketalization. Four different variants were made, differing in the nature of the acyl side chain with respect to the length, and in the number and stereochemistry of the double bonds. Moderate biological activity was observed for the derivatives with a side chain based on palmitic acid and linoleic acid.

van der Kaaden, Marjolein; Breukink, Eefjan

2012-01-01

236

Potentiation of azole antifungals by 2-adamantanamine.  

PubMed

Azoles are among the most successful classes of antifungals. They act by inhibiting ?-14 lanosterol demethylase in the ergosterol biosynthesis pathway. Oropharyngeal candidiasis (OPC) occurs in about 90% of HIV-infected individuals, and 4 to 5% are refractory to current therapies, including azoles, due to the formation of resistant biofilms produced in the course of OPC. We reasoned that compounds affecting a different target may potentiate azoles to produce increased killing and an antibiofilm therapeutic. 2-Adamantanamine (AC17) was identified in a screen for compounds potentiating the action of miconazole against biofilms of Candida albicans. AC17, a close structural analog to the antiviral amantadine, did not affect the viability of C. albicans but caused the normally fungistatic azoles to become fungicidal. Transcriptome analysis of cells treated with AC17 revealed that the ergosterol and filamentation pathways were affected. Indeed, cells exposed to AC17 had decreased ergosterol contents and were unable to invade agar. In vivo, the combination of AC17 and fluconazole produced a significant reduction in fungal tissue burden in a guinea pig model of cutaneous candidiasis, while each treatment alone did not have a significant effect. The combination of fluconazole and AC17 also showed improved efficacy (P value of 0.018) compared to fluconazole alone when fungal lesions were evaluated. AC17 is a promising lead in the search for more effective antifungal therapeutics. PMID:23689724

Lafleur, Michael D; Sun, Lingmei; Lister, Ida; Keating, John; Nantel, Andre; Long, Lisa; Ghannoum, Mahmoud; North, Jeffrey; Lee, Richard E; Coleman, Ken; Dahl, Thomas; Lewis, Kim

2013-08-01

237

Synergistic Antifungal Effect of Glabridin and Fluconazole  

PubMed Central

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.

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

238

Susceptibility of Prototheca Species to Antifungal Agents  

PubMed Central

Twenty isolates of Prototheca filamenta, Prototheca moriformis, Prototheca stagnora, Prototheca wickerhamii, and Prototheca zopfii were tested for in vitro susceptibility to five commonly used antifungal agents: amphotericin B, 5-fluorocytosine, griseofulvin, miconazole, and nystatin. The results revealed resistance to griseofulvin of all the Prototheca isolates tested and an inhibitory effect on P. filamenta by high 5-fluorocytosine concentrations (minimal inhibitory concentration [MIC] = 12.5 to 100 ?g/ml; minimal fungicidal or algacidal concentration [MFC/MAC] = 50 to 100 ?g/ml). P. filamenta isolates were also susceptible to miconazole (MIC = 0.1 to 0.5 ?g/ml, MFC/MAC = 0.5 to 1 ?g/ml); isolates of the other Prototheca species varied in regard to miconazole activity from susceptible to resistant (MIC = 1 ? >100 ?g/ml, MFC/MAC = 5 ? >100 ?g/ml). The Prototheca isolates revealed an in vitro susceptibility to the polyene antifungal agents, amphotericin B, and nystatin (MIC = 0.09 to 3.12 ?g/ml and 0.19 to 12.5 ?g/ml, respectively; MFC/MAC = 0.19 to 25 ?g/ml and 0.75 to 25 ?g/ml, respectively).

Segal, Ester; Padhye, Arvind A.; Ajello, Libero

1976-01-01

239

Susceptibility of Prototheca species to antifungal agents.  

PubMed

Twenty isolates of Prototheca filamenta, Prototheca moriformis, Prototheca stagnora, Prototheca wickerhamii, and Prototheca zopfii were tested for in vitro susceptibility to five commonly used antifungal agents: amphotericin B, 5-fluorocytosine, griseofulvin, miconazole, and nystatin. The results revealed resistance to griseofulvin of all the Prototheca isolates tested and an inhibitory effect on P. filamenta by high 5-fluorocytosine concentrations (minimal inhibitory concentration [MIC] = 12.5 to 100 mug/ml; minimal fungicidal or algacidal concentration [MFC/MAC] = 50 to 100 mug/ml). P. filamenta isolates were also susceptible to miconazole (MIC = 0.1 to 0.5 mug/ml, MFC/MAC = 0.5 to 1 mug/ml); isolates of the other Prototheca species varied in regard to miconazole activity from susceptible to resistant (MIC = 1 - >100 mug/ml, MFC/MAC = 5 - >100 mug/ml). The Prototheca isolates revealed an in vitro susceptibility to the polyene antifungal agents, amphotericin B, and nystatin (MIC = 0.09 to 3.12 mug/ml and 0.19 to 12.5 mug/ml, respectively; MFC/MAC = 0.19 to 25 mug/ml and 0.75 to 25 mug/ml, respectively). PMID:984758

Segal, E; Padhye, A A; Ajello, L

1976-07-01

240

Pharmacokinetics and pharmacodynamics of antifungals in children: clinical implications.  

PubMed

Invasive fungal disease (IFD) remains life threatening in premature infants and immunocompromised children despite the recent development of new antifungal agents. Optimal dosing of antifungals is one of the few factors clinicians can control to improve outcomes of IFD. However, dosing in children cannot be extrapolated from adult data because IFD pathophysiology, immune response, and drug disposition differ from adults. We critically examined the literature on pharmacokinetics (PK) and pharmacodynamics (PD) of antifungal agents and highlight recent developments in treating pediatric IFD. To match adult exposure in pediatric patients, dosing adjustment is necessary for almost all antifungals. In young infants, the maturation of renal and metabolic functions occurs rapidly and can significantly influence drug exposure. Fluconazole clearance doubles from birth to 28 days of life and, beyond the neonatal period, agents such as fluconazole, voriconazole, and micafungin require higher dosing than in adults because of faster clearance in children. As a result, dosing recommendations are specific to bracketed ranges of age. PD principles of antifungals mostly rely on in vitro and in vivo models but very few PD studies specifically address IFD in children. The exposure-response relationship may differ in younger children compared with adults, especially in infants with invasive candidiasis who are at higher risk of disseminated disease and meningoencephalitis, and by extension severe neurodevelopmental impairment. Micafungin is the only antifungal agent for which a specific target of exposure was proposed based on a neonatal hematogenous Candida meningoencephalitis animal model. In this review, we found that pediatric data on drug disposition of newer triazoles and echinocandins are lacking, dosing of older antifungals such as fluconazole and amphotericin B products still need optimization in young infants, and that target PK/PD indices need to be clinically validated for almost all antifungals in children. A better understanding of age-specific PK and PD of new antifungals in infants and children will help improve clinical outcomes of IFD by informing dosing and identifying future research areas. PMID:24872147

Autmizguine, Julie; Guptill, Jeffrey T; Cohen-Wolkowiez, Michael; Benjamin, Daniel K; Capparelli, Edmund V

2014-06-01

241

Antifungal drug development: challenges, unmet clinical needs, and new approaches.  

PubMed

Invasive, life-threatening fungal infections are an important cause of morbidity and mortality, particularly for patients with compromised immune function. The number of therapeutic options for the treatment of invasive fungal infections is quite limited when compared with those available to treat bacterial infections. Indeed, only three classes of molecules are currently used in clinical practice and only one new class of antifungal drugs has been developed in the last 30 years. Here we summarize the unmet clinical needs of current antifungal therapy, discuss challenges inherent to antifungal drug discovery and development, and review recent developments aimed at addressing some of these challenges. PMID:24789878

Roemer, Terry; Krysan, Damian J

2014-01-01

242

Overview of medically important antifungal azole derivatives.  

PubMed

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

Fromtling, R A

1988-04-01

243

Antifungal 3-butylisocoumarins from Asteraceae-Anthemideae.  

PubMed

Seven new naturally occurring 3-butylisocoumarins were isolated and identified from lipophilic extracts of aerial as well as underground organs: corfin (17) and 3'-hydroxycorfin (18) from the roots of Chamaemelum mixtum and (-)-(R)-2'-methoxydihydroartemidin (5), (+)-(S,R)-epoxyartemidin (6a), dracumerin (12), (+)-(R)-(E)-3'-hydroxyartemidin (13), and capillarin isovalerate (20) from various organs of Artemisia dracunculus (tarragon). Furthermore, six known derivatives, artemidiol (7), (E/Z)-artemidin (11), capillarin (19), artemidinol (21), 8-hydroxyartemidin (22), and 8-hydroxycapillarin (23), were obtained. The antifungal activities of all naturally occurring derivatives were determined in a germ-tube inhibition test against a susceptible strain of rice blast fungus Pyricularia grisea. The 3-butyl side-chain is a prerequisite for high activity. Eleven structurally related synthetic derivatives were additionally tested to explore the influence of structural characteristics on activity. Benlate, blasticidin S, kresoxim-methyl, griseofulvin, and the carrot phytoalexin 6-methoxymellein all served as positive controls. PMID:14738379

Engelmeier, D; Hadacek, F; Hofer, O; Lutz-Kutschera, G; Nagl, M; Wurz, G; Greger, H

2004-01-01

244

A new antifungal metabolite from Penicillium expansum.  

PubMed

A new antifungal compound, (3S)-4,6-dihydro-8-methoxy-3,5-dimethyl-6-oxo-3H-2-benzopyran (4), was isolated from Penicillium expansum. During the isolation procedure 4 was determined to be unstable and readily reacted with methanol, ethanol, and water, forming three new isochromans, (1S,3S)-6-hydroxy-1,8-dimethoxy-3,5-dimethylisochroman (1), 1-ethoxy-6-hydroxy-8-methoxy-3,5-dimethylisochroman (2), and 1,6-dihydroxy-8-methoxy-3,5-dimethylisochroman (3), respectively. (3S)-6-Hydroxy-8-methoxy-3,5-dimethylisochroman (5) was reisolated from P. expansum. In fungicide disk assays, compounds 1, 2, and 4 inhibited the mycelial growth of Lasiodiplodia theobromae at 100 microg/mL by 76%, 74%, and 69%, respectively. PMID:15270557

He, Guochun; Matsuura, Hideyuki; Takushi, Tetsuya; Kawano, Shinji; Yoshihara, Teruhiko

2004-07-01

245

Overview of medically important antifungal azole derivatives.  

PubMed Central

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).

Fromtling, R A

1988-01-01

246

Canadian perspectives on antifungal treatment for onychomycosis.  

PubMed

Onychomycosis is a common nail disease caused by dermatophytes, yeasts, and nondermatophyte molds affecting approximately 6.5% of the Canadian population. Approved therapies for onychomycosis in Canada are terbinafine 250 mg once daily for 6 to 12 weeks; itraconazole 200 mg twice daily given for two to three pulses (one pulse = 200 mg daily for 1 week, with 3 weeks off the drug before the next pulse); and ciclopirox nail lacquer 8% used once daily for up to 48 weeks. These medications can be used for dermatophyte onychomycosis of toenails or fingernails. Liver enzyme monitoring should be performed when prescribing the oral medications. Ciclopirox is one of the newest antifungal agents and is the only topical therapy specifically indicated for onychomycosis in Canada. Topical therapy for onychomycosis provides an advantage over oral treatment in safety and cost, giving ciclopirox wide potential for use. It remains to be seen what future role ciclopirox will have in the Canadian onychomycosis spectrum. PMID:17204230

Gupta, Aditya K; Poulin, Yves; Lynde, Charles W

2006-12-01

247

Candicidin and other polyenic antifungal antibiotics  

PubMed Central

About 50 polyenic antifungal antibiotics produced by actinomycetes have been isolated and described. Among these are the most effective antimonilial agents so far known. These polyenes can be classified into four broad groups depending on the number of conjugated carbon-to-carbon double bonds that are present in their chromophores. Only some of the tetraenes (four conjugated double bonds), such as nystatin and pimaricin, and a few heptaenes (seven conjugated double bonds), such as amphotericin B, Trichomycin candicidin and hamycin, have found practical application in the treatment of infectious diseases caused by fungi. Nystatin and pimaricin show the least in vitro activity against fungi, while trichomycin and candicidin are the most active. Recent clinical investigations carried out in the USA have shown that candicidin is very effective in the treatment of vaginal monilial infections.

Waksman, Selman A.; Lechevalier, Hubert A.; Schaffner, Carl P.

1965-01-01

248

Antifungal potential of Indian medicinal plants.  

PubMed

Fourteen Indian plants, selected based on their use in respiratory and other disorders in traditional systems of medicine, were analyzed for their potential activity against fungi. The antifungal activity was investigated by disc diffusion, microbroth dilution and percent spore germination inhibition tests against pathogenic Aspergilli. Methanolic extracts of Solanum xanthocarpum and Datura metel inhibited the growth of Aspergillus fumigatus, A. flavus and A. niger and their in vitro MICs were found to be 1.25-2.50 mg/ml by both microbroth dilution and percent spore germination assays. In disc diffusion assay, a concentration of 0.062 mg/disc of methanol extract of D. metel showed significant activity against Aspergilli. S. xanthocarpum exhibited similar activity at 0.125 mg/disc. PMID:15159003

Dabur, Rajesh; Singh, H; Chhillar, A K; Ali, M; Sharma, G L

2004-06-01

249

Antifungal therapy for chronic rhinosinusitis: the controversy persists  

PubMed Central

Purpose of review Chronic rhinosinusitis is a debilitating disease seen frequently by allergist–immunologists. Recent research examining the pathophysiological mechanisms and treatment options for chronic rhinosinusitis have yielded contradicting results, particularly in regard to the role of fungi and antifungal therapies. Recent findings Recent studies using antifungal therapies for chronic rhinosinusitis will be critically evaluated with careful attention to sample selection, length of the intervention, drug delivery system, drug stability and handling, assessment of compliance to study medications, and choice of outcome measures with attention to study power (both primary and secondary). Using this framework to evaluate currently available studies reveals limitations in studies showing a benefit for antifungal therapy and in studies showing no benefit (or harm). Summary Limitations in studies that either support or refute the benefit of antifungal therapy for chronic rhinosinusitis prevent any firm conclusions about its efficacy.

Rank, Matthew A.; Adolphson, Cheryl R.; Kita, Hirohito

2014-01-01

250

Research to Identify Effective Antifungal Agents, 1993 Annual Report.  

SciTech Connect

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.

Schreck, Carl

1993-10-01

251

Research to Identify Effective Antifungal Agents, 1991 Annual Report.  

SciTech Connect

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.

Schreck, Carl

1991-09-01

252

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

PubMed

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. PMID:20363517

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

2010-07-01

253

Chemical structure and antifungal activity of a number of triterpenoids.  

PubMed

Antifungal activity was tested in 49 pentacyclic triterpenoids and their glycosides, of plant and semisynthetic origin. Several of these compounds inhibited the multiplication of the yeast Saccharomyces carlsbergensis. The highest antifungal activity was found in the triterpene glycosides oleanolic acid and hederagenin, which have a free carboxyl group at C 28(27). Triterpenes of the meristotropic acid, macedonic acid, and lupan types had no fungistatic activity at concentrations up to 100 microgram/ml. PMID:549682

Anisimov, M M; Shcheglov, V V; Strigina, L I; Chetyrina, N S; Uvarova, N I; Oshitok, G I; Alad'ina, N G; Vecherko, L P; Zorina, A D; Matyukhina, L G; Saltykova, I A

1979-01-01

254

Recent insights into the mechanisms of antifungal resistance  

Microsoft Academic Search

The incidence of fungal infections has increased in recent years, particularly among immunocompromised individuals. Treatment\\u000a of invasive fungal infections has been hampered by a limited number of available antifungal agents and both intrinsic and\\u000a acquired resistance to these agents among many fungal pathogens. Therefore, much interest has focused on elucidating the molecular\\u000a basis for antifungal resistance. Recent efforts have increased

Katherine S. Barker; P. David Rogers

2006-01-01

255

[Antifungal susceptibility testing in yeasts. Update and novelties].  

PubMed

This text reviews and updates the uses of the reference procedures for antifungal susceptibility testing in yeasts, the reliability of the commercial methods and the guidelines for the use of these procedures for patient management and for epidemiological reasons to determine the susceptibility profile and the emergence of resistances. Novelties in the procedures of setting clinical breakpoints of antifungal agents by both the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the US Clinical Laboratory Standards Institute (CLSI) are also reviewed. PMID:23453232

Cuenca-Estrella, Manuel; Alastruey-Izquierdo, Ana; Gómez-López, Alicia; Monzón, Araceli

2013-02-01

256

Chemosensitization as a Means to Augment Commercial Antifungal Agents  

PubMed Central

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.

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

2012-01-01

257

Antituberculosis activity of certain antifungal and antihelmintic drugs  

Microsoft Academic Search

A panel of antifungal and antihelmintic drugs was tested for activity against Mycobacterium tuberculosis in vitro. Antifungal drugs, miconazole, 2-nitroimidazole, clotrimazole, and the antihelmintic drug niclosamide were found to have significant antituberculosis activity, with minimal inhibitory concentrations (MICs) between 1 and 10?g\\/ml. Niclosamide and 2-nitroimidazole also had activity against stationary phase tubercle bacilli. Further testing of these drugs and their

Z. Sun; Y. Zhang

1999-01-01

258

Isolation of Bacillus amyloliquefaciens Strains with Antifungal Activities from Meju  

PubMed Central

Bacilli with fibrinolytic activities were isolated from traditionally-prepared Meju and some of these strains showed strong antifungal activities. One isolate, MJ1-4, showed the strongest antifungal activity. MJ1-4 and other isolates were identified as B. amyloliquefaciens strains by recA gene sequencing and RAPD-PCR results. B. amyloliqufaciens MJ1-4 efficiently inhibited an Aspergillus spp.-producing aflatoxin B1 (AFB1) and a Penicillium spp.-producing ochratoxin (OTA) in addition to other fungi. Antifungal activity of B. amyloliquefaciens MJ1-4 culture reached its maximum (40 AU/mg protein) in LB or TSB medium around 48 hr at 37°C. Antifungal activity of the concentrated culture supernatant was not decreased significantly by protease treatments, implying that the antifungal substance might not be a simple peptide or protein. Considering its antifungal and fibrinolytic activities together, B. amyloliquefaciens MJ1-4 can serve as a starter for fermented soyfoods such as Cheonggukjang and Doenjang.

Lee, Hwang A; Kim, Jeong Hwan

2012-01-01

259

Synthesis and antifungal activity of benzimidazole, benzotriazole and aminothiazole derivatives  

PubMed Central

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.

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

2012-01-01

260

In vivo mutagenicity of conazole fungicides correlates with tumorigenicity.  

PubMed

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 tests. We studied the in vivo mutagenicity of these three conazoles using the Big Blue mouse assay system. Groups of mice were fed either control diet or diet containing 1800 p.p.m. triadimefon, 2500 p.p.m. propiconazole or 2000 p.p.m. myclobutanil. After 4 days of feeding, mice were immediately euthanized, livers were removed, DNA isolated and lacI genes recovered into infectious bacteriophage lambda particles by in vitro packaging. Bacteriophage with mutations in the lacI gene was detected by infecting into Escherichia coli, and mutant frequencies were determined using a colorimetric plaque assay. Propiconazole induced a 1.97-fold increase in mutant frequency compared to concurrent controls (P = 0.018) and triadimefon induced a 1.94-fold increase compared to concurrent controls (P = 0.009). Myclobutanil did not induce any change in mutant frequency (P = 0.548). These results provide the first evidence that the hepatotumorigenic conazoles are capable of inducing mutations in liver in vivo while the non-tumorigen myclobutanil is not, suggesting that mutagenicity may represent a key event in conazoles tumorigenic mode of action. PMID:19028983

Ross, Jeffrey A; Moore, Tanya; Leavitt, Sharon A

2009-03-01

261

Solid-state structure determination and solution-state NMR characterization of the (2 R ,4 R )\\/(2 S ,4 S )- and (2 R ,4 S )\\/(2 S ,4 R )-diastereomers of the agricultural fungicide propiconazole, the (2 R ,4 S )\\/(2 S ,4 R )-symmetrical triazole constitutional isomer, and a ditriazole analogue  

Microsoft Academic Search

Single-crystal X-ray diffraction analysis was used to determine the structure of a racemic diastereomer of the agricultural fungicide propiconazole [1-(2-(2,4-dichlorophenyl)-4-n-propyl-1,3-dioxolane-2-yl-methyl)-1-H-1,2,4-triazole] and of two by-products (a symmetrical 1,3,4-triazole racemic-constitutional isomer and a propiconazole ditriazole analogue). All three crystalline racemic-diastereomers had (2R,4S)\\/(2S,4R)-stereochemistry in which then-propyl group was observed in atrans-to-phenyl disposition. Propiconazole (2R,4S)\\/(2S,4R)-diastereomer gives crystals belonging to the monoclinic space group P21,\\/a,

Robert Glaser; Itay Adin; David Ovadia; Ernestine Mendler; Marc Drouin

1995-01-01

262

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

PubMed

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

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

2013-03-01

263

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

PubMed Central

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.

Asmundsdottir, Lena Ros; Erlendsdottir, Helga

2013-01-01

264

[Textiles with antifungal and antibacterial properties].  

PubMed

SeaCell and SeaCell active fibers can be produced on the basis of the ZIMMER Lyocell process. One particularity of the SeaCell fiber is its capacity to bind and absorb substances. During the activation of SeaCell fibers the bactericidal metal silver is absorbed by the fully formed cellulosic fiber through metalsorption. The present study demonstrates the antifungal and antibacterial effect of SeaCell active in an in vitro test system against Candida albicans (DSM 11225), Candida tropicalis (ATCC 1169) and Candida krusei (ATCC 6258). Furthermore, the antibacterial activity of fibers with different amounts of SeaCell active fibers in a dose-dependent manner against Staphylococcus aureus (ATCC 22923) and Escherichia coli (ATCC 35218) could be demonstrated. If this fiber seems to be suited for bio-active textiles in specific anatomical body regions and skin conditions with a susceptibility for fungal and bacterial infections namely with Candida species, Staphylococcus aureus and Escherichia coli must be examined by means of further investigations, especially in vivo tests in human considering allergic and toxic effects of the fiber. PMID:18782244

Hipler, U C

2008-09-01

265

Antifungal Hydrolases in Pea Tissue 1  

PubMed Central

Chitinase and ?-1,3-glucanase purified from pea pods acted synergistically in the degradation of fungal cell walls. The antifungal potential of the two enzymes was studied directly by adding protein preparations to paper discs placed on agar plates containing germinated fungal spores. Protein extracts from pea pods infected with Fusarium solani f.sp. phaseoli, which contained high activities of chitinase and ?-1,3-glucanase, inhibited growth of 15 out of 18 fungi tested. Protein extracts from uninfected pea pods, which contained low activities of chitinase and ?-1,3-glucanase, did not inhibit fungal growth. Purified chitinase and ?-1,3-glucanase, tested individually, did not inhibit growth of most of the test fungi. Only Trichoderma viride was inhibited by chitinase alone, and only Fusarium solani f.sp. pisi was inhibited by ?-1,3-glucanase alone. However, combinations of purified chitinase and ?-1,3-glucanase inhibited all fungi tested as effectively as crude protein extracts containing the same enzyme activities. The pea pathogen, Fusarium solani f.sp. pisi, and the nonpathogen of peas, Fusarium solani f.sp. phaseoli, were similarly strongly inhibited by chitinase and ?-1,3-glucanase, indicating that the differential pathogenicity of the two fungi is not due to differential sensitivity to the pea enzymes. Inhibition of fungal growth was caused by the lysis of the hyphal tips. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5

Mauch, Felix; Mauch-Mani, Brigitte; Boller, Thomas

1988-01-01

266

Cynodontin: a fungal metabolite with antifungal properties.  

PubMed

A red pigment that accumulates in cultures of a Drechslera avenae pathotype with specificity for Avena sterilis was isolated and identified as the anthraquinone cynodontin (3-methyl-1,4,5,8-tetrahydroxyanthraquinone). Satisfactory yield of the compound was obtained with 20-60 day incubations at temperatures between 20 and 27 degrees C. Cynodontin was tested in vitro for fungitoxicity and was found to be a potent inhibitor of the growth of Sclerotinia minor, Sclerotinia sclerotiorum, and Botrytis cinerea and, to a lesser extent, of Verticillium dahliae. The ED(50) values obtained with these fungi were of the same order of magnitude as those of the commercial fungicides dicloran and carbendazim, which were used as reference chemicals. In contrast, the growth of a number of other fungi was not significantly inhibited by cynodontin. Anthraquinone and two other anthraquinone derivatives, emodin and chrysophanol, which were also included in the tests, did not affect the growth of the cynodontin-sensitive fungi. It thus appears that the type and position of the substitutions at the C-ring play a role in the expression of antifungal activity. PMID:12903946

Chrysayi-Tokousbalides, Maria; Kastanias, Michael A

2003-08-13

267

Update on antifungal therapy with terbinafine.  

PubMed

Terbinafine, a synthetic antifungal of allylamine class, has fungicidal activity against dermatophytes, moulds and certain dimorphic fungi and fungistatic activity against Candida albicans. Following oral administration the terbinafine is absorbed rapidly (>70%) and reaches within 2 hours the peak plasma concentration. The drug is highly lipophilic and keratophilic and is highly bound to plasma protein (>90%) with a bioavailability of 70% to 80%. The drug is rapidly delivered and it is present in the stratum corneum, sebum, nails and hair for months after stopping the medication. The drug has been proven to be the choice treatment in the therapy of onychomycosis as it is very effective, well tolerated and has a relatively low potential for drug interactions. The pharmacologic and pharmacokinetic properties of terbinafine give strong support to the possibility that the pulse therapy may be equally effective in onychomycoses, possibly reducing medication costs and drug exposure. Several therapeutic patterns have been proposed: weekly intermittent terbinafine (500 mg/d for 1 week each month for 4 months), or single-dose terbinafine (1000 mg per month for 4 months). Use of topical terbinafine 1% may be practical where the tinea involvement is not extensive or chronic. Recently, the terbinafine is available in a novel topical solution (film-forming solution--FFS) effective in the treatment of tinea pedis (athlete's foot). PMID:20461049

Gianni, C

2010-06-01

268

Update on antifungal resistance in Aspergillus and Candida.  

PubMed

Antifungal resistance in Candida and Aspergillus may be either intrinsic or acquired and may be encountered in the antifungal drug exposed but also the antifungal drug-naïve patient. Prior antifungal treatment confers a selection pressure and notoriously raises the awareness of possible resistance in patients failing therapy, thus calling for susceptibility testing. On the contrary, antifungal resistance in the drug-naïve patient is less expected and therefore more challenging. This is particularly true when it concerns pathogens with acquired resistance which cannot be predicted from the species identification itself. This scenario is particularly relevant for A. fumigatus infections due to the increasing prevalence of azole-resistant isolates in the environment. For Candida, infections resistance is most common in the context of increasing prevalence of species with intrinsic resistance. Candida glabrata which has intrinsically reduced susceptibility to fluconazole is increasingly common particularly among the adult and elderly population on the Northern Hemisphere where it may be responsible for as many as 30% of the blood stream infections in population-based surveillance programmes. Candida parapsilosis is prevalent in the paediatric setting, at centres with increasing echinocandin use and at the southern or pacific parts of the world. In the following, the prevalence and drivers of intrinsic and acquired resistance in Aspergillus and Candida will be reviewed. PMID:24372701

Arendrup, M C

2014-06-01

269

Antifungal activity of multifunctional Fe 3O 4-Ag nanocolloids  

NASA Astrophysics Data System (ADS)

In recent years, rapid increase has been observed in the population of microbes that are resistant to conventionally used antibiotics. Antifungal drug therapy is no exception and now resistance to many of the antifungal agents in use has emerged. Therefore, there is an inevitable and urgent medical need for antibiotics with novel antimicrobial mechanisms. Aspergillus glaucus is the potential cause of fatal brain infections and hypersensitivity pneumonitis in immunocompromised patients and leads to death despite aggressive multidrug antifungal therapy. In the present article, we describe the antifungal activity of multifunctional core-shell Fe 3O 4-Ag nanocolloids against A. glaucus isolates. Controlled experiments are also carried out with Ag nanocolloids in order to understand the role of core (Fe 3O 4) in the antifungal action. The minimum inhibitory concentration (MIC) of nanocolloids is determined by the micro-dilution method. MIC of A. glaucus is 2000 ?g/mL. The result is quite promising and requires further investigations in order to develop a treatment methodology against this death causing fungus in immunocompromised patients.

Chudasama, Bhupendra; Vala, Anjana K.; Andhariya, Nidhi; Upadhyay, R. V.; Mehta, R. V.

2011-05-01

270

Cadinene sesquiterpenes from Eupatorium adenophorum and their antifungal activity.  

PubMed

Bioactive constituents of Eupatorium adenophorum were investigated for antifungal activity. A structure-antifungal activity relationship of cadinene sesquiterpenes was predicted by evaluating individual derivatives. Cadinene derivatives were extracted from leaves of Eupatorium adenophorum using ethyl acetate. Five cadinene sesquiterpenes were isolated by column chromatography and Preparative Thin Layer Chromatography. Bioactivity of these cadinene sesquiterpenes were evaluated in vitro against four phytopathogenic fungi using poison food technique. Purified sesquiterpenes were spectroscopically elucidated as cadinan-3-ene-2,7-dione (1), 7-hydroxycadinan-3-ene-2-one (2), 5,6-dihydroxycadinan-3-ene-2,7-dione (3), cadinan-3,6-diene-2,7-dione (4) and 2-acetyl-cadinan-3,6-diene-7-one (5). Antifungal evaluation of these compounds against pathogenic fungi was found to be selective. Compound 1 was highly inhibitory towards S. rolfsii (ED50 181.60 ± 0.58 ?gmL(-1)) and R. solani (ED50 189.74 ± 1.03 ?gmL(-1)). Availability of plant material and significant antifungal activity makes the plant a potential source of antifungal agent and that can be exploited for the development of a natural fungicide. PMID:23452218

Kundu, Aditi; Saha, Supradip; Walia, Suresh; Shakil, Najam A; Kumar, Jitendra; Annapurna, Kannepalli

2013-01-01

271

In Search of the Holy Grail of Antifungal Therapy  

PubMed Central

The ideal antifungal agent remains an elusive goal for treatment of life-threatening systemic fungal infections. Such an agent would have broad antifungal activity, low rates of resistance, flexible routes of administration, few associated adverse events, and limited drug-drug interactions. Only three of the seven classes of antifungal agents currently available are suitable for treatment of systemic infection: the polyenes, the azoles, and the echinocandins. None match all the characteristics of an ideal agent, the Holy Grail of antifungal therapy. Academia and industry need to collaborate in the search for new lead antifungal compounds using traditional screening methods as well as the new pharmacogenomics methods. Enhancing efficacy and reducing toxicity of the currently available therapeutic agents is also another important avenue of study. As an example, the Mycosis Research Center at the University of Mississippi Medical Center has identified pyogenic polyenes in commercial preparations of amphotericin B deoxycholate which correlate with infusion related toxicities. A highly purified formulation of amphotericin B appears promising, with a better therapeutic index compared to its parent compound as evidenced by results of in vitro and in vivo studies reviewed in this presentation.

Chapman, Stanley W.; Sullivan, Donna C.; Cleary, John D.

2008-01-01

272

New targets and delivery systems for antifungal therapy.  

PubMed

Development of new approaches for treatment of invasive fungal infections encompasses new delivery systems for approved and investigational compounds, as well as exploiting the cell membrane, cell wall and virulence factors as putative antifungal targets. Novel delivery systems consisting of cyclodextrins, cochleates, nanoparticles/nanospheres and long circulating ('stealth') liposomes, substantially modulate the pharmacokinetics of existing compounds, and may also be useful to enhance the delivery of antifungal agents to sites of infection. Further insights into the structure-activity relationship of the antifungal triazoles that target the biosynthesis of ergosterol in the fungal cell membrane have led to the development of highly potent broad spectrum agents, including posaconazole, ravuconazole and voriconazole. Similarly, a novel generation of cell-wall active semisynthetic echinocandin 1,3 beta-glucan inhibitors (caspofungin, FK463, and VER-002) has entered clinical development. These agents have potent and broad-spectrum activity against Candida spp, and potentially useful activity against Aspergillus spp. and Pneumocystis carinii. The ongoing convergence of the fields of molecular pathogenesis, antifungal pharmacology and vaccine development will afford the opportunity to develop novel targets to complement the existing antifungal armamentarium. PMID:11204162

Walsh, T J; Viviani, M A; Arathoon, E; Chiou, C; Ghannoum, M; Groll, A H; Odds, F C

2000-01-01

273

Antifungal mechanism of the Aspergillus giganteus AFP against the rice blast fungus Magnaporthe grisea  

Microsoft Academic Search

The mold Aspergillus giganteus produces a basic, low molecular weight protein showing antifungal properties against economically important plant pathogens, the AFP (Antifungal Protein). In this study, we investigated the mechanisms by which AFP exerts its antifungal activity against Magnaporthe grisea. M. grisea is the causal agent of rice blast, one of the most devastating diseases of cultivated rice worldwide. AFP

Ana Beatriz Moreno; Blanca San Segundo

274

Use of the Sensititre Colorimetric Microdilution Panel for Antifungal Susceptibility Testing of Dermatophytes  

Microsoft Academic Search

The Sensititre YeastOne antifungal panel was used to test 49 dermatophytes belonging to the species Epidermophyton floccosum, Microsporum gypseum, Microsporum canis, Trichophyton tonsurans, Trichophyton rubrum, and Trichophyton mentagrophytes. The MICs of four antifungals obtained with the Sensititre YeastOne antifungal panel were compared with those obtained by the reference NCCLS microdilution method. The levels of agreement between the two methods (<2

I. Pujol; J. Capilla; B. Fernandez-Torres; M. Ortoneda; J. Guarro

2002-01-01

275

Proficiency Testing Program for Clinical Laboratories Performing Antifungal Susceptibility Testing of Pathogenic Yeast Species  

Microsoft Academic Search

Antifungal susceptibility testing is expected to facilitate the selection of adequate therapy for fungal infec- tions. The general availability of antifungal susceptibility testing in clinical laboratories is low, even though a number of standard methods are now available. The objective of the present study was to develop and evaluate a proficiency testing program (PTP) for the antifungal susceptibility testing of

Rama Ramani; Vishnu Chaturvedi

2003-01-01

276

Proficiency Testing Program for Clinical Laboratories Performing Antifungal Susceptibility Testing of Pathogenic Yeast Species  

Microsoft Academic Search

Antifungal susceptibility testing is expected to facilitate the selection of adequate therapy for fungal infec- tions. The general availability of antifungal susceptibility testing in clinical laboratories is low, even though a number of standard methods are now available. The objective of the present study was to develop and evaluate a proficiency testing program (PTP) for the antifungal susceptibility testing of

Rama Ramani; Vishnu Chaturvedi

277

Antifungal activity of sakurasosaponin from the root extract of Jacquinia flammea.  

PubMed

The methanolic crude extract from the roots of Jacquinia flammea showed moderate antifungal activity against dermatophytes and very strong antifungal activity against Colletotrichum gloeosporioides. The bioassay-guided purification of the extract, using a combination of vacuum-liquid chromatography and high performance liquid chromatography, allowed the identification of sakurasosaponin as the main metabolite responsible for the antifungal activity. PMID:21740284

García-Sosa, K; Sánchez-Medina, A; Álvarez, Sandra L; Zacchino, S; Veitch, N C; Simá-Polanco, P; Peña-Rodriguez, L M

2011-07-01

278

Antifungal resistance does not necessarily affect Candida glabrata fitness.  

PubMed

Although there has been an overall good coverage of Candida glabrata infections by the echinocandins, emergence of antifungal resistance during therapy has been reported. We investigated, by using an invertebrate host model, the fitness of sequential C. glabrata isolates with different echinocandins susceptibility patterns. The studied strains were isolated from a case of recurrent fungemia with a fatal outcome due to C. glabrata that developed cross-resistance to echinocandins during caspofungin therapy. The sequential strains isolated post-therapy showed a S663P mutation in the Fks2p hot spot 1. In vivo study in the invertebrate host Galleria mellonella did not suggest a fitness cost related to the acquired antifungal resistance, the three isolates displayed a similar rate of killing (P ?=? 0.54). We observed a clear correlation between emergence of antifungal resistance and persistence of the causal agent, probably aided by the unchanged fitness and unresponsiveness in vivo to the adopted therapy. PMID:24091025

Borghi, Elisa; Andreoni, Stefano; Cirasola, Daniela; Ricucci, Valentina; Sciota, Rita; Morace, Giulia

2014-02-01

279

Antifungal compounds from the rhizome and roots of Ferula hermonis.  

PubMed

The antifungal activity of hexane, dichloromethane, methanol and aqueous extracts from the rhizome and root of Ferula hermonis was assayed in vitro by the agar disk diffusion method against a panel of human opportunistic and pathogenic fungi. Among them, the hexane and dichloromethane extracts showed the highest activity particularly against the dermatophytes Microsporum gypseum and Tricophyton mentagrophytes as well as the yeast Candida lactis-condensi. Activity-guided fractionation of both extracts using an agar overlay bioautographic method led to the isolation of two antifungal compounds which were identified as the daucane aryl esters jaeschkeanadiol p-hydroxybenzoate (ferutinin) and jaeschkeanadiol benzoate (teferidin). Determination of minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) values of both compounds evidenced a stronger antifungal activity for ferutinin than for teferidin. Particularly, T. mentagrophytes was the most sensitive strain with MIC and MFC values ranging from 8 to 256 µg/mL. PMID:22927102

Al-Ja'fari, Abdel-Hadi; Vila, Roser; Freixa, Blanca; Costa, Joan; Cañigueral, Salvador

2013-06-01

280

Comparison of antifungal activities of Vietnamese citrus essential oils.  

PubMed

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. PMID:22799453

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

2013-03-01

281

Enhancement of Commercial Antifungal Agents by Kojic Acid  

PubMed Central

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., sakA?, mpkC?, 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.

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

2012-01-01

282

Antimicrobial and antifungal effects of tissue conditioners containing a photocatalyst.  

PubMed

This study examined the antimicrobial/antifungal ability of a tissue conditioner containing a photocatalyst for Escherichia coli, Streptococcus mutans, Staphylococcus aureus and Candida albicans. The photocatalyst was mixed with tissue conditioners powders at concentrations of 0, 10, 15, and 20 wt%. Tissue conditioners powders containing a photocatalyst were mixed with liquid to make test specimens. Test specimens inoculated by each microorganism were irradiated by ultraviolet light for 0-, 2- and 4 hours. The antimicrobial/antifungal effects were evaluated by the CFU technique. The CFU values of each microorganism for tissue conditioners containing a photocatalyst showed significant decrease following UV-irradiation. The improvement in antimicrobial/antifungal effects was concomitant with the increase of the mixing ratio and the irradiation time. Therefore, the results indicated that tissue conditioners containing a photocatalyst might have photocatalytic ability. PMID:21946490

Uchimaru, Masayuki; Sakai, Takako; Moroi, Ryoji; Shiota, Susumu; Shibata, Yukie; Deguchi, Mikito; Sakai, Hidetaka; Yamashita, Yoshihisa; Terada, Yoshihiro

2011-01-01

283

Antifungal properties of yam (Dioscorea alata) peel extract.  

PubMed

The extraction of natural antifungal compounds from the peels of yam (Dioscorea alata) and the effect of these compounds on both the vegetative and reproductive structures of some yam not pathogens were studied. Four prominent antifungal components were obtained; one of the components was fully characterized and identified as beta-sitosterol. The antifungal activity of the compounds toward the germination of spores of two yam pathogens showed an inhibition of less than 57% at a concentration of 50 mg/L while inhibition on the elongation of germ-tubes of Fusarium moniliforme was as high as 82% at the same concentration. However, the ED50 for inhibition of germ-tube elongation in the yam compounds for the same organism was below 32 mg/L. The role of the yam compounds at high concentrations in disease resistance is discussed. PMID:9173001

Aderiye, B I; Ogundana, S K; Adesanya, S A; Roberts, M F

1996-01-01

284

Antifungal activity of alkyl gallates against plant pathogenic fungi.  

PubMed

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. PMID:24618299

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

2014-04-01

285

Peptide-based Antifungal Therapies against Emerging Infections  

PubMed Central

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.

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

2010-01-01

286

Caenorhabditis elegans-based Model Systems for Antifungal Drug Discovery  

PubMed Central

The substantial morbidity and mortality associated with invasive fungal infections constitute undisputed tokens of their severity. The continued expansion of susceptible population groups (such as immunocompromised individuals, patients undergoing extensive surgery, and those hospitalized with serious underlying diseases especially in the intensive care unit) and the limitations of current antifungal agents due to toxicity issues or to the development of resistance, mandate the development of novel antifungal drugs. Currently, drug discovery is transitioning from the traditional in vitro large-scale screens of chemical libraries to more complex bioassays, including in vivo studies on whole animals; invertebrates, such as Caenorhabditis elegans, are thus gaining momentum as screening tools. Key pathogenesis features of fungal infections, including filament formation, are expressed in certain invertebrate and mammalian hosts; among the various potential hosts, C. elegans provides an attractive platform both for the study of host-pathogen interactions and the identification of new antifungal agents. Advantages of compound screening in this facile, relatively inexpensive and not as ethically challenged whole-animal context, include the simultaneous assessment of antifungal efficacy and toxicity that could result in the identification of compounds with distinct mechanisms of action, for example by promoting host immune responses or by impeding fungal virulence factors. With the recent advent of using predictive models to screen for compounds with improved chances of bioavailability in the nematode a priori, high-throughput screening of chemical libraries using the C. elegans-c. albicans antifungal discovery assay holds even greater promise for the identification of novel antifungal agents in the near future.

Anastassopoulou, Cleo G.; Fuchs, Beth Burgwyn; Mylonakis, Eleftherios

2013-01-01

287

Influence of human serum on antifungal pharmacodynamics with Candida albicans.  

PubMed

Antifungal susceptibilities (NCCLS, approved standard M27-A, 1997) were determined for the reference strain ATCC 90028 and 21 clinical isolates of Candida albicans with varying levels of fluconazole susceptibility using RPMI 1640 (RPMI) and 80% fresh human serum-20% RPMI (serum). Sixty-four percent (14 of 22) of the isolates tested demonstrated significant decreases (> or = 4-fold) in fluconazole MICs in the presence of serum, and the remaining eight isolates exhibited no change. Itraconazole and ketoconazole, two highly protein-bound antifungal agents, had MICs in serum that were increased or unchanged for 46% (10 of 22) and 41% (9 of 22) of the isolates, respectively. All 10 isolates tested against an investigational antifungal agent, LY303366, demonstrated significant increases in the MIC required in serum, while differences in amphotericin B MICs in the two media were not observed. Four of 10 isolates tested demonstrated fourfold higher flucytosine MICs in serum than in RPMI. Postantifungal effects (PAFEs) and 24-h kill curves were determined by standard methods for selected isolates. At the MIC, fluconazole, itraconazole, ketoconazole, flucytosine, and LY303366 kill curves and PAFEs in RPMI were similar to those in serum. Isolates of fluconazole-resistant C. albicans required lower MICs in serum than in RPMI, without relative increases in fungal killing or PAFEs. Isolates tested against amphotericin B demonstrated significantly reduced killing and shorter PAFEs in serum than in RPMI without observable changes in MIC. In conclusion, antifungal pharmacodynamics in RPMI did not consistently predict antifungal activity in serum for azoles and amphotericin B. Generally speaking, antifungal agents with high protein binding exhibited some form of reduced activity (MIC, killing, or PAFE) in the presence of serum compared to those with low protein binding. PMID:11408217

Zhanel, G G; Saunders, D G; Hoban, D J; Karlowsky, J A

2001-07-01

288

Influence of Human Serum on Antifungal Pharmacodynamics with Candida albicans  

PubMed Central

Antifungal susceptibilities (NCCLS, approved standard M27-A, 1997) were determined for the reference strain ATCC 90028 and 21 clinical isolates of Candida albicans with varying levels of fluconazole susceptibility using RPMI 1640 (RPMI) and 80% fresh human serum–20% RPMI (serum). Sixty-four percent (14 of 22) of the isolates tested demonstrated significant decreases (?4-fold) in fluconazole MICs in the presence of serum, and the remaining eight isolates exhibited no change. Itraconazole and ketoconazole, two highly protein-bound antifungal agents, had MICs in serum that were increased or unchanged for 46% (10 of 22) and 41% (9 of 22) of the isolates, respectively. All 10 isolates tested against an investigational antifungal agent, LY303366, demonstrated significant increases in the MIC required in serum, while differences in amphotericin B MICs in the two media were not observed. Four of 10 isolates tested demonstrated fourfold higher flucytosine MICs in serum than in RPMI. Postantifungal effects (PAFEs) and 24-h kill curves were determined by standard methods for selected isolates. At the MIC, fluconazole, itraconazole, ketoconazole, flucytosine, and LY303366 kill curves and PAFEs in RPMI were similar to those in serum. Isolates of fluconazole-resistant C. albicans required lower MICs in serum than in RPMI, without relative increases in fungal killing or PAFEs. Isolates tested against amphotericin B demonstrated significantly reduced killing and shorter PAFEs in serum than in RPMI without observable changes in MIC. In conclusion, antifungal pharmacodynamics in RPMI did not consistently predict antifungal activity in serum for azoles and amphotericin B. Generally speaking, antifungal agents with high protein binding exhibited some form of reduced activity (MIC, killing, or PAFE) in the presence of serum compared to those with low protein binding.

Zhanel, George G.; Saunders, David G.; Hoban, Daryl J.; Karlowsky, James A.

2001-01-01

289

Use of Antifungal Combination Therapy: Agents, Order, and Timing  

PubMed Central

Given the substantial morbidity and mortality related to invasive fungal infections, treatment with a combination of antifungal agents is often considered. A growing body of literature from in vitro studies, animal models, and clinical experience provides data evaluating this approach. This review describes combination antifungal strategies for the management of cryptococcal meningitis, invasive candidiasis, invasive aspergillosis, and rare mold infections. The potential effects that sequencing and timing have on the efficacy of such approaches are discussed, with a focus on recent clinical data in this arena.

Perfect, John R.

2010-01-01

290

Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani  

PubMed Central

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.

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

291

Antifungal and antioxidant activities of the phytomedicine pipsissewa, Chimaphila umbellata  

Microsoft Academic Search

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

Imelda J. Galván; Nadereh Mir-Rashed; Matthew Jessulat; Monica Atanya; Ashkan Golshani; Tony Durst; Philippe Petit; Virginie Treyvaud Amiguet; Teun Boekhout; Richard Summerbell; Isabel Cruz; John T. Arnason; Myron L. Smith

2008-01-01

292

Antifungal activity of hydrochloride salts of tylophorinidine and tylophorinine.  

PubMed

The antimicrobial efficacy of two phenanthroindolizidine alkaloids, tylophorinidine hydrochloride (TdnH) and tylophorinine hydrochloride (TnnH), isolated from the plant Tylophora indica (local name, Antamul) was evaluated. These were screened for in vitro antifungal and antibacterial activities. Both compounds exhibited potent antifungal activity displaying minimum inhibitory concentrations (MIC) in the range of 2-4 microg/mL for TdnH and 0.6-2.5 microg/mL for TnnH against Candida species. PMID:23074899

Dhiman, Mini; Parab, Rajashri R; Manju, Sreedharannair L; Desai, Dattatraya C; Mahajan, Girish B

2012-09-01

293

Atmospheric pressure cold plasma as an antifungal therapy  

SciTech Connect

A microhollow cathode based, direct-current, atmospheric pressure, He/O{sub 2} (2%) cold plasma microjet was used to inactive antifungal resistants Candida albicans, Candida krusei, and Candida glabrata in air and in water. Effective inactivation (>90%) was achieved in 10 min in air and 1 min in water. Antifungal susceptibility tests showed drastic reduction of the minimum inhibitory concentration after plasma treatment. The inactivation was attributed to the reactive oxygen species generated in plasma or in water. Hydroxyl and singlet molecular oxygen radicals were detected in plasma-water system by electron spin resonance spectroscopy. This approach proposed a promising clinical dermatology therapy.

Sun Peng; Wu Haiyan [College of Engineering, Peking University, Beijing 100871 (China); Sun Yi; Liu Wei; Li Ruoyu [Department of Dermatology and Venereology, Peking Univ. 1st Hospital and Research Center for Medical Mycology, Peking Univ., Beijing 100034 (China); Zhu Weidong; Lopez, Jose L. [Department of Applied Science and Technology and Center for Microplasma Science and Technology, Saint Peter's College, Jersey City, New Jersey 07306 (United States); Zhang Jue; Fang Jing [College of Engineering, Peking University, Beijing 100871 (China); Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China)

2011-01-10

294

Novel antifungal defensins from Nigella sativa L. seeds.  

PubMed

From seeds of Nigella sativa L. (Ranunculaceae), an endemic plant of Uzbekistan, two novel defensins named Ns-D1 and Ns-D2, were isolated and sequenced. The peptides differ by a single amino acid residue and show high sequence similarity to Raphanus sativus L. defensins Rs-AFP1 and Rs-AFP2. The Ns-D1 and Ns-D2 defensins display strong although divergent antifungal activity towards a number of phytopathogenic fungi. High antifungal activity of N. sativa defensins makes them promising candidates for engineering pathogen-resistant plants. PMID:21144761

Rogozhin, Eugene A; Oshchepkova, Yulia I; Odintsova, Tatyiana I; Khadeeva, Natalia V; Veshkurova, Olga N; Egorov, Tsezi A; Grishin, Eugene V; Salikhov, Shavkat I

2011-02-01

295

Triazole induced drought tolerance in horse chestnut (Aesculus hippocastanum).  

PubMed

We determined the influence of the triazole derivatives paclobutrazol, penconazole, epixiconazole, propiconazole and myclobutanil on the drought tolerance and post drought recovery of container-grown horse chestnut (Aesculus hippocastanum L.) saplings. Myclobutanil neither conferred drought resistance, as assessed by its effects on a number of physiological and biochemical parameters, nor affected growth parameters measured after recovery from drought. Chlorophyll fluorescence (F(v)/F(m)), photosynthetic rates, total foliar chlorophyll and carotenoid concentrations, foliar proline concentration and superoxide dismutase and catalase activities were consistently higher and leaf necrosis and cellular electrolyte leakage was lower at the end of a 3-week drought in trees treated with paclobutrazol, penconazole, epixiconazole or propiconazole than in control trees. Twelve weeks after drought treatment, leaf area and shoot, root and total plant dry masses were greater in triazole-treated trees than in control trees with the exception of those treated with myclobutanil. In a separate study, trees were subjected to a 2-week drought and then sprayed with paclobutrazol, penconazole, epixiconazole, propiconazole or myclobutanil. Chlorophyll fluorescence, photosynthetic rate, foliar chlorophyll concentration and catalase activity over the following 12 weeks were 20 to 50% higher in triazole-treated trees than in control trees. At the end of the 12-week recovery period, leaf area and shoot, root and total plant dry masses were higher in triazole-treated trees than in control trees, with the exception of trees treated with myclobutanil. Application of triazole derivatives, with the exception of myclobutanil, enhanced tolerance to prolonged drought and, when applied after a 2-week drought, hastened recovery from drought. The magnitude of treatment effects was in the order epixiconazole approximately propiconazole > penconazole > paclobutrazol > myclobutanil. PMID:18765373

Percival, Glynn C; Noviss, Kelly

2008-11-01

296

Polyelectrolyte Multilayers Fabricated from Antifungal ?-Peptides: Design of Surfaces that Exhibit Antifungal Activity Against Candida albicans  

PubMed Central

The fungal pathogen Candida albicans can form biofilms on the surfaces of medical devices that are resistant to drug treatment and provide a reservoir for recurrent infections. The use of fungicidal or fungistatic materials to fabricate or coat the surfaces of medical devices has the potential to reduce or eliminate the incidence of biofilm-associated infections. Here, we report on (i) the fabrication of multilayered polyelectrolyte thin films (PEMs) that promote the surface-mediated release of an antifungal ?-peptide and (ii) the ability of these films to inhibit the growth of C. albicans on film-coated surfaces. We incorporated a fluorescently labeled antifungal ?-peptide into the structures of PEMs fabricated from poly-L-glutamic acid (PGA) and poly-L-lysine (PLL) using a layer-by-layer fabrication procedure. These films remained stable when incubated in culture media at 37 °C and released ?-peptide gradually into solution for up to 400 hours. Surfaces coated with ?-peptide-containing films inhibited the growth of C. albicans, resulting in a 20% reduction of cell viability after two hours and a 74% decrease in metabolic activity after seven hours when compared to cells incubated on PGA/PLL coated surfaces. In addition, ?-peptide-containing films inhibited hyphal elongation by 55%. These results, when combined, demonstrate that it is possible to fabricate ?-peptide-containing thin films that inhibit the growth and proliferation of C. albicans and provide the basis of an approach that could be used to inhibit the formation of C. albicans biofilms on film-coated surfaces. The layer-by-layer approach reported here could ultimately be used to coat the surfaces of catheters, surgical instruments, and other devices to inhibit drug-resistant C. albicans biofilm formation in clinical settings.

Karlsson, Amy J.; Flessner, Ryan M.; Gellman, Samuel H.

2010-01-01

297

Combination Antifungal Therapy for Cryptococcal Meningitis  

PubMed Central

BACKGROUND Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. METHODS We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. RESULTS A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P = 0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P = 0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P = 0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P = 0.13). amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (?0.42 log10 colony-forming units [CFU] per milliliter per day vs. ?0.31 and ?0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy. CONCLUSIONS Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found. (Funded by the Wellcome Trust and the British Infection Society; Controlled-Trials.com number, ISRCTN95123928.)

Day, Jeremy N.; Chau, Tran T.H.; Wolbers, Marcel; Mai, Pham P.; Dung, Nguyen T.; Mai, Nguyen H.; Phu, Nguyen H.; Nghia, Ho D.; Phong, Nguyen D.; Thai, Cao Q.; Thai, Le H.; Chuong, Ly V.; Sinh, Dinh X.; Duong, Van A.; Hoang, Thu N.; Diep, Pham T.; Campbell, James I.; Sieu, Tran P.M.; Baker, Stephen G.; Chau, Nguyen V.V.; Hien, Tran T.

2014-01-01

298

Human Pharmacogenomic Variations and Their Implications for Antifungal Efficacy  

PubMed Central

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.

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

2006-01-01

299

Antibodies, killer toxins and antifungal immunoprotection: a lesson from nature?  

Microsoft Academic Search

Cellular immunity if usually considered the principal defence mechanism against human opportunistic fungi. Recently, detection of protective antibodies has provoked a resurgence of interest in humoral immunity as critical to antifungal protection. In particular, the discovery of human natural fungicidal antibodies acting as internal images of yeast killer toxins has highlighted the importance of the idiotypic network and has suggested

Anatonio Cassone; Flavia De Bernardis; Stefania Conti; Luciano Polonelli

1997-01-01

300

Standardization of Antifungal Susceptibility Variables for a Semiautomated Methodology  

Microsoft Academic Search

Recently, the methodology that will serve as a basis of the standard for antifungal susceptibility testing of fermentative yeasts of the European Committee on Antibiotic Susceptibility Testing has been described. This procedure employs a spectrophotometric method for both inoculum adjustment and endpoint determination. However, the utilization of a spectrophotometer requires studies for standardization. The present work analyzes the following parameters:

JUAN L. RODRIGUEZ-TUDELA; MANUEL CUENCA-ESTRELLA; TERESA M. DIAZ-GUERRA; EMILIA MELLADO

2001-01-01

301

Collaborative Evaluation of Optimal Antifungal Susceptibility Testing Conditions for Dermatophytes  

Microsoft Academic Search

A multicenter study was conducted to define the most suitable testing conditions for antifungal susceptibility of dermatophytes. Broth microdilution MICs of clotrimazole, itraconazole, and terbinafine were determined in three centers against 60 strains of dermatophytes. The effects of inoculum density (ca. 10 3 and 10 4 CFU\\/ml), incubation time (3, 7, and 14 days), endpoint criteria for MIC determination (complete

Belkys Fernandez-Torres; Francisco J. Cabanes; Alfonso J. Carrillo-Munoz; Alexandre Esteban; Isabel Inza; Lourdes Abarca; Josep Guarro

2002-01-01

302

Antifungal Activity of Eupolauridine and Its Action on DNA Topoisomerases  

Microsoft Academic Search

The azafluoranthene alkaloid eupolauridine has previously been shown to have in vitro antifungal activity and selective inhibition of fungal topoisomerase I. The present study was undertaken to examine further its selectivity and mode of action. Eupolauridine completely inhibits the DNA relaxation activity of purified fungal topoisomerase I at 50 g\\/ml, but it does not stabilize the cleavage complex of either

Shabana I. Khan; Alison C. Nimrod; Mohammed Mehrpooya; John L. Nitiss; Larry A. Walker; Alice M. Clark

2002-01-01

303

Research to Identify Effective Antifungal Agents, 1992 Annual Report.  

SciTech Connect

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.

Schreck, Carl

1993-03-01

304

Research to identify effective antifungal agents. Annual report 1993.  

National Technical Information Service (NTIS)

Use of malachite green as a fungicide in fish culture was terminated by the Food and Drug Administration (FDA) on August 27,1991. Formalin has been the replacement antifungal agent, but the present registration restricts its use only to eggs of salmonids ...

C. B. Schreck M. S. Fitzpatric R. L. Chitwood L. L. Marking J. J. Rach

1993-01-01

305

Invasive fungal infection — laboratory diagnosis and antifungal treatment  

Microsoft Academic Search

Invasive fungal infections (IFIs) have become increasingly prevalent in the recent decade along with the increasing populations of immunocompromised patients and widespread use of the broad-spectrum antibiotics. The morbidity and the mortality of IFIs remain high while the diagnosis and treatment of IFIs are highly challenging. Recent advances in diagnostic methods and antifungal agents provide the potential to improve the

Pei-Lan Shao; Li-Min Huang; Po-Ren Hsueh

2006-01-01

306

Antifungal properties of the human Metschnikowia strain IHEM 25107.  

PubMed

Metschnikowiaceae may show natural, strain-dependent antifungal properties, so they are employed in agriculture as natural, safe alternatives to pesticides. With this paper, we documented the ability of the recently described Metschnikowia IHEM 25107 to inhibit growth of several molds, including diverse Aspergillus species and dermatophytes. This biocontrol activity enables pulcherrimin-producing strains to naturally antagonize competing microorganisms. PMID:24272547

Sisti, Maurizio; Savini, Vincenzo

2014-05-01

307

Molecular epidemiology and antifungal susceptibility of Serbian Cryptococcus neoformans isolates.  

PubMed

Molecular typing and antifungal susceptibility testing of 34 clinical Serbian Cryptococcus neoformans isolates from 25 patients was retrospectively performed. Amplified fragment length polymorphism (AFLP) fingerprinting was used for genotyping, whereas a novel real-time PCR was used to determine the mating- and serotype. The antifungals amphotericin B, 5-fluorocytosine, fluconazole, voriconazole, itraconazole and posaconazole were used to determine the antifungal susceptibility profiles. The majority of isolates belonged to genotype AFLP1/VNI (n = 20; 58.8%), followed by AFLP2/VNIV (n = 10; 29.4%), AFLP3/VNIII (n = 3; 8.8%) and AFLP1B/VNII (n = 1; 2.9%). All AFLP1/VNI isolates were mating-serotype ?A, the sole AFLP1B/VNII isolate was found to be aA, whereas AFLP2/VNIV harboured serotype D isolates with either the a (n = 2; 5.9%) or ? (n = 8; 23.5%) mating-type allele. The isolates (n = 3; 8.8%) that were found to be genotype AFLP3/VNIII had the hybrid mating- and serotype combination aA-?D. In vitro antifungal susceptibility testing showed that all isolates were susceptible to amphotericin B, voriconazole and posaconazole. Low resistance level was observed for fluconazole (n = 1; 2.9%) and 5-fluorocytosine. (n = 2; 5.8%). A large percentage of isolates was found to be susceptible dose dependent to itraconazole (n = 16; 47.1%). AFLP1/VNI was the most common genotype among clinical C. neoformans isolates from immunocompromised patients in Serbia. C. neoformans from HIV-negative patients were significantly less susceptible to 5-fluorocytosine (P < 0.01). Correlation between genotypes and antifungal susceptibility was not observed. PMID:24438323

Arsic Arsenijevic, Valentina; Pekmezovic, Marina G; Meis, Jacques F; Hagen, Ferry

2014-06-01

308

High-performance chiral separation of fourteen triazole fungicides by sulfated ?-cyclodextrin-mediated capillary electrophoresis  

Microsoft Academic Search

In this paper, sulfated ?-cyclodextrin-mediated capillary electrophoresis (CE) is evaluated as a new approach for the chiral separation of triazole-type fungicides. The 14 fungicides investigated were bitertanol, cyproconazole, difenoconazole, diniconazole, flutriafol, hexaconazole, myclobutanil, paclobutrazol, penconazole, propiconazole, tebuconazole, tetraconazole, triadimefon and triadimenol. Under the optimal conditions, excellent enantioseparation was achieved for all the 14 fungicides, including those fungicides containing two chiral

Y. S. Wu; H. K. Lee; S. F. Y. Li

2001-01-01

309

Effect of conazole fungicides on reproductive development in the female rat  

Microsoft Academic Search

Three triazole fungicides were evaluated for effects on female rat reproductive development. Rats were exposed via feed to propiconazole (P) (100, 500, or 2500ppm), myclobutanil (M) (100, 500, or 2000ppm), or triadimefon (T) (100, 500, or 1800ppm) from gestation day 6 to postnatal day (PND) 98. Body weight (BW) and anogenital distance (AGD) at PND 0, age and BW at

John C. Rockett; Michael G. Narotsky; Kary E. Thompson; Inthirany Thillainadarajah; Chad R. Blystone; Amber K. Goetz; Hongzu Ren; Deborah S. Best; Rachel N. Murrell; Harriette P. Nichols; Judith E. Schmid; Douglas C. Wolf; David J. Dix

2006-01-01

310

Gene expression profiling in liver and testis of rats to characterize the toxicity of triazole fungicides  

Microsoft Academic Search

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 for hormone measurements, and liver and testes were collected for histology, enzyme biochemistry, or gene expression profiling. Body and testis weights were unaffected, but

Douglas B. Tully; Wenjun Bao; Amber K. Goetz; Chad R. Blystone; Hongzu Ren; Judith E. Schmid; Lillian F. Strader; Carmen R. Wood; Deborah S. Best; Michael G. Narotsky; Douglas C. Wolf; John C. Rockett; David J.. Dix

2006-01-01

311

The effect of fungicides on urediniospore germination and disease development of daylily rust  

Microsoft Academic Search

In response to the recent introduction and rapid spread throughout the United States of daylily rust caused by Puccinia hemerocallidis, research was conducted on the relative efficacy of seven fungicides (myclobutanil, propiconazole, flutolanil, triadimefon, chlorothalonil, mancozeb, and azoxystrobin) for control of this disease. Fungicides were applied at varying rates 24h before spray–inoculation of daylilies (Hemerocallis sp. cv. Pardon Me) with

J. W Buck; J. L Williams-Woodward

2003-01-01

312

Decline of pesticide residues from barley to malt  

Microsoft Academic Search

The fate of dinitroaniline herbicides (pendimethalin and trifluralin), organophosphous insecticides (fenitrothion and malathion), and pyrimidine (nuarimol) and triazole (myclobutanil and propiconazole) fungicides from barley to malt was determined. Several samples for residue analysis were taken after each stage of malting (steeping, germination and kilning). Pesticide residue analysis was carried out by GC\\/ITMS in selected ion monitoring mode. Pesticides decline along

S. Navarro; G. Pérez; G. Navarro; N. Vela

2007-01-01

313

Baseline sensitivity and cross-resistance to demethylation-inhibiting fungicides in Ontario isolates of Sclerotinia homoeocarpa  

Microsoft Academic Search

Four hundred and thirty-five isolates of Sclerotinia homoeocarpa from eight populations in southern Ontario were tested for sensitivity to the demethylation-inhibiting (DMI) fungicides, propiconazole, myclobutanil, fenarimol and tebuconazole. The isolates were collected in summer 1994 just prior to legal DMI fungicide use on turfgrass in Ontario. There were wide variations in sensitivities, and seven of the eight populations were very

T. Hsiang; L. Yang; W. Barton

1997-01-01

314

Evaluation of selected fungicides to control mint rust on Scotch spearmint  

Microsoft Academic Search

Mint rust, caused by the fungus Puccinia menthae, is a serious disease limiting the establishment of a viable spearmint oil industry in north east Victoria, Australia. Six fungicide-active ingredients: bitertanol, triadimenol, fluquinconazole, tebuconazole, myclobutanil and propiconazole, were evaluated for control of this disease. Bitertanol gave the most effective control resulting in higher oil yields, followed by tebuconazole. Fluquinconazole was the

J Edwards; F. E Bienvenu

2000-01-01

315

Extension of the bioautograph technique for multiresidue determination of fungicide residues in plants and water  

Microsoft Academic Search

The inhibition effect of 17 fungicides on spores germination of different species of fungi on thin layer Chromatographie (TLC) plates has been studied in order to extend the applicability of bioautography and to increase the sensitivity of the detection. Minimum detectable amounts on TLC plates of vinclozolin, iprodione, procymidone, captan, imazalil, triadimefon, triadimenol, fenarimol, propiconazole, myclobutanil, flutriafol, flusilazole, hexaconazole, tebuconazole,

Anna Balinova

1995-01-01

316

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...

317

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  

Microsoft Academic Search

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

M. A. Pfaller; D. J. Diekema; S. A. Messer; L. Boyken; H. Huynh; R. J. Hollis

2002-01-01

318

In vitro screening of 10 edible thai plants for potential antifungal properties.  

PubMed

Growing rates of fungal infections and increasing resistance against standard antifungal drugs can cause serious health problems. There is, therefore, increasing interest in the potential use of medicinal plants as novel antifungal agents. This study investigates the antifungal properties of crude plant extracts from ten medicinal plant species. Crude samples were extracted using the hot water extraction process. The minimum inhibitory concentrations (MIC) and diameter zone of inhibition were determined in each extract against ten fungal strains, and fluconazole was used as a positive control. The cytotoxicity of crude extracts on in vitro human skin fibroblast (HSF) cell models was determined by MTT assay. Of the ten crude extracts, Psidium guajava L. exhibited the highest antifungal activity, diameter zone of inhibition, and percentage HSF cell viability. Although all extracts exhibited antifungal activity, Psidium guajava L. had the greatest potential for developing antifungal treatments. PMID:24516502

Suwanmanee, Supattra; Kitisin, Thitinan; Luplertlop, Natthanej

2014-01-01

319

How does antifungal pharmacology differ for mucormycosis versus aspergillosis?  

PubMed

Over the last decade, advances in diagnostic systems and the introduction of new antifungal agents have significantly improved outcomes in immunocompromised patients who develop invasive aspergillosis. However, mortality rates remain relatively unchanged for less common, but highly aggressive, mold infections such as mucormycosis. Recent genome sequencing of Rhizopus oryzae revealed evidence of a whole-genome duplication event during the evolution of this pathogen. Consequently, R. oryzae has a 2- to 10-fold enrichment in gene families associated with ergosterol and cell wall biosynthesis, cell growth, iron uptake, and known fungal virulence factors compared with sequenced Aspergillus fumigatus strains. This genetic plasticity may explain the remarkable capability of this pathogen for rapid growth in hostile environments, such as the inflammatory milieu, as well as its relative resistance to multiple antifungal classes. Herein, we examine how pharmacological aspects of treating mucormycosis may differ from those of the more commonly encountered invasive aspergillosis. PMID:22247448

Lewis, Russell E; Lortholary, Olivier; Spellberg, Brad; Roilides, Emmanuel; Kontoyiannis, Dimitrios P; Walsh, Thomas J

2012-02-01

320

Pharmacognostic and antifungal investigations of Elaeocarpus ganitrus (Rudrakasha)  

PubMed Central

Rudrakasha is the dried bead obtained from the ripe fruit of Elaeocarpus ganitrus Roxb. (Family: Elaeocarpaceae). Microscopic studies revealed the presence of a hard endocarp with lignified isodiametric sclereids, seeds with membranous seed coat, which enclosed a dense cellular endosperm comprising of calcium oxalate druses. Physicochemical parameters showed that total ash was 1.36 times and 1.56 times more than the acid insoluble ash and water-soluble ash, respectively. Further, ethanol had a maximum extractable value of 2.4% and moisture content was found to be 9.7%. Different extracts, petroleum ether, chloroform, ethanol and water were prepared. Chemically the extracts showed the presence of phytosterols, fats, alkaloids, flavonoids, carbohydrates, proteins and tannins. The extracts were evaluated for antifungal activity on different fungal strains. Chlorofom and ethanol extracts have high antifungal activity against Candida albicans. Whereas, chloroform, ethanol and water extracts showed moderate inhibition against Aspergillus niger.

Singh, B.; Chopra, A.; Ishar, M.P.S.; Sharma, A.; Raj, T.

2010-01-01

321

Rondonin an antifungal peptide from spider (Acanthoscurria rondoniae) haemolymph  

PubMed Central

Antimicrobial activities were detected in the haemolymph of the spider Acanthoscurrria rondoniae. A novel antifungal peptide, rondonin, was purified by reverse phase high performance liquid chromatography (RP-HPLC). Rondonin has an amino acid sequence of IIIQYEGHKH and a molecular mass of 1236.776 Da. This peptide has identity to a C-terminal fragment of the “d” subunit of haemocyanin from the spiders Eurypelma californicum and Acanthoscurria gomesiana. A synthetic peptide mimicking rondonin had identical characteristics to those of the isolated material, confirming its sequence. The synthetic peptide was active only against fungus. These data led us to conclude that the antifungal activity detected in the plasma of these spiders is the result of enzymatic processing of a protein that delivers oxygen in the haemolymph of many chelicerate. Several studies have suggested that haemocyanins are involved in the arthropod immune system, and the activity of this haemocyanin fragment reinforces this idea.

Riciluca, K.C.T.; Sayegh, R.S.R.; Melo, R.L.; Silva, P.I.

2012-01-01

322

Antifungal Textiles Formed Using Silver Deposition in Supercritical Carbon Dioxide  

NASA Astrophysics Data System (ADS)

The antifungal properties of two silver-coated natural cotton fiber structures prepared using a supercritical carbon dioxide (scCO2) solvent were examined. Scanning electron microscopy confirmed that the scCO2 process may be used to produce cotton fiber textiles with uniform silver nanoparticle coatings. A version of the Kirby-Bauer disk diffusion test was used to assess the ability of these textiles to inhibit fungal growth. Cotton fabric samples modified with Ag(hepta) and Ag(cod)(hfac) exhibited measurable zones of inhibition. On the other hand, the uncoated fabric had no zone of inhibition. Possible applications of antifungal textiles prepared using scCO2 processing include use in hospital uniforms and wound dressings.

Gittard, Shaun D.; Hojo, Daisuke; Hyde, G. Kevin; Scarel, Giovanna; Narayan, Roger J.; Parsons, Gregory N.

2010-04-01

323

Conventional and alternative antifungal therapies to oral candidiasis.  

PubMed

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

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

2010-10-01

324

Antifungal activity of Stenotrophomonas maltophilia in Stomoxys calcitrans larvae.  

PubMed

The microbiota present in Stomoxys calcitrans larvae may assist their survival in contaminated environments through production of inhibitory substances. Bacteriological identification methods, the polymerase chain reaction (PCR) and scanning electron microscopy (SEM) were used to detect a bacterium naturally present in mucus and macerated S. calcitrans larvae. The antifungal activity was determined based on the results from disk diffusion tests on an artificial solid medium. The bacterium was identified as Stenotrophomonas maltophilia and presented antifungal activity against Beauveria bassiana sensu lato isolates CG 138, CG 228 and ESALQ 986. This result suggests that the larval microbiota is a factor that can compromise the use of B. bassiana s.l. fungus for biological control of S. calcitrans larvae. PMID:25054498

Moraes, Ana Paula Rodrigues; Videira, Sandy Sampaio; Bittencourt, Vânia Rita Elias Pinheiro; Bittencourt, Avelino José

2014-04-01

325

Antifungal metabolites from fungal endophytes of Pinus strobus.  

PubMed

The extracts of five foliar fungal endophytes isolated from Pinus strobus (eastern white pine) that showed antifungal activity in disc diffusion assays were selected for further study. From these strains, the aliphatic polyketide compound 1 and three related sesquiterpenes 2-4 were isolated and characterized. Compound 2 is reported for the first time as a natural product and the E/Z conformational isomers 3 and 4 were hitherto unknown. Additionally, the three known macrolides; pyrenophorol (5), dihydropyrenophorin (6), and pyrenophorin (7) were isolated and identified. Their structures were elucidated by spectroscopic analyses including 2D NMR, HRMS and by comparison to literature data where available. The isolated compounds 1, 2, and 5 were antifungal against both the rust Microbotryum violaceum and Saccharomyces cerevisae. PMID:21632082

Sumarah, Mark W; Kesting, Julie R; Sørensen, Dan; Miller, J David

2011-10-01

326

Conventional and alternative antifungal therapies to oral candidiasis  

PubMed Central

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.

Anibal, Paula Cristina; de Cassia Orlandi Sardi, Janaina; Peixoto, Iza Teixeira Alves; de Carvalho Moraes, Julianna Joanna; Hofling, Jose Francisco

2010-01-01

327

Efinaconazole solution 10%: topical antifungal therapy for toenail onychomycosis.  

PubMed

Toenail onychomycosis is a common disease with limited treatment options, as treatment failures and relapses frequently are encountered. Many patients experience long-term disease that affects multiple toenails and causes substantial discomfort and pain. Although many patients prefer topical therapies, treatment efficacy with ciclopirox and amorolfine lacquers has been disappointing. Efinaconazole solution 10% is a new triazole antifungal agent specifically developed for the treatment of onychomycosis. Efinaconazole has shown a broad spectrum of antifungal activity in vitro and is more potent than ciclopirox against common onychomycosis pathogens. It has lower keratin binding and quicker drug release from keratin than ciclopirox and amorolfine and exhibits remarkably greater in vivo activity. Efinaconazole has limited or no potential for drug interactions and a low resistance potential. Efinaconazole provides a viable alternative to oral therapy for the treatment of toenail onychomycosis. PMID:24195094

Tosti, Antonella

2013-10-01

328

Antifungal action of the oxathiolone-fused chalcone derivative.  

PubMed

AMG-148, an oxathiolone-fused chalcone derivative, exhibited in vitro antifungal activity against several strains of human pathogenic yeast, with minimum inhibitory concentration values within the range of 1-16 ?g ml(-1) and a fungicidal effect was observed at higher concentrations. Presence of major drug-effluxing membrane proteins Cdr1p, Cdr2p or Mdr1p, did not affect substantially the fungistatic activity of this compound against clinical Candida albicans strains. Studies on the mode of action revealed that AMG-148 inhibited chitin and ?(1?3)glucan biosynthesis and was in vitro an inhibitor of ?(1?3)glucan synthase. Inhibition of chitin biosynthesis was responsible for fungistatic activity, while the fungicidal effect was a consequence of disturbance of ?(1?3)glucan synthase function. The chalcone derivative may be a useful lead compound for the development of novel antifungal agents. PMID:21910757

??cka, Izabela; Konieczny, Marek T; Bu?akowska, Anita; Rzymowski, Tomasz; Milewski, S?awomir

2011-09-01

329

Lectins but not antifungal proteins exhibit anti-nematode activity.  

PubMed

A variety of lectins and antifungal proteins were tested for toxicity against the plant parasitic nematodes Ditylenchus dipsaci and Heterodera glycines. It was found that lectins from the mushrooms Xylaria hypoxylon, Agrocybe cylindracea and Tricholoma mongolicum (TML-1) were the most potent against D. dipsaci, with EC(50) being 4.7, 9, and 20mg/ml, respectively. Lectins from Pseudostellaria heterophylla, samta tomato, and the mushrooms T. mongolicum (TML-2), Ganoderma lucidum, and Boletus edulis, and antifungal proteins from Ginkgo biloba toward D. dipsaci and pumpkin Cucurbita moschata had much lower anti-nematode potencies and could be considered as inactive for practical purposes. All lectins except that from P.heterophylle were potent against H.glycines. PMID:21784014

Zhao, S; Guo, Y X; Liu, Q H; Wang, H X; Ng, T B

2009-09-01

330

Antifungal agents and therapy for infants and children with invasive fungal infections: a pharmacological perspective  

PubMed Central

Invasive fungal infections, although relatively rare, are life-threatening diseases in premature infants and immunocompromised children. While many advances have been made in antifungal therapeutics in the last two decades, knowledge of the pharmacokinetics and pharmacodynamics of antifungal agents for infants and children remains incomplete. This review summarizes the pharmacology and clinical utility of currently available antifungal agents and discusses the opportunities and challenges for future research.

Lestner, Jodi M; Smith, P Brian; Cohen-Wolkowiez, Michael; Benjamin, Daniel K; Hope, William W

2013-01-01

331

The Mediterranean red alga Asparagopsis taxiformis has antifungal activity against Aspergillus species.  

PubMed

The red algae Asparagopsis taxiformis collected from the Straits of Messina (Italy) were screened for antifungal activity against Aspergillus species. EUCAST methodology was applied and extracts showed antifungal activity against A. fumigatus, A. terreus and A. flavus. The lowest minimum inhibitory concentrations observed were <0.15 mg ml(-1) and the highest were >5 mg ml(-1) for Aspergillus spp. tested. Agar diffusion assays confirmed antifungal activity of A. taxiformis extracts in Aspergillus species. PMID:23437896

Genovese, Giuseppa; Leitner, Sandra; Minicante, Simona A; Lass-Flörl, Cornelia

2013-09-01

332

Antifungal cyclopeptides from Halobacillus litoralis YS3106 of marine origin  

Microsoft Academic Search

Three new cyclopeptides, including halolitoralin A (a cyclic hexapeptide), halolitoralin B and C (two cyclic tetrapeptides), together with three known cyclic dipeptides, cyclo(Pro-Val), cyclo(Pro-Leu) and cyclo(Ile-Val) were isolated from the ferment broth of a marine sediment-derived Halobacillus litoralis YS3106. The cyclopeptides show surprisingly simple architectures with highly repeated residue units, which showed moderate antifungal and weak antitumor activities in vitro.

Ling Yang; Ren-xiang Tan; Qian Wang; Wei-yi Huang; Yong-xian Yin

2002-01-01

333

Cordymin, an antifungal peptide from the medicinal fungus Cordyceps militaris  

Microsoft Academic Search

Cordymin, an antifungal peptide with a molecular mass of 10,906Da and an N-terminal amino acid sequence distinct from those of previously reported proteins, was purified from the medicinal mushroom Cordyceps militaris. The isolation protocol comprised ion exchange chromatography of the aqueous extract on SP-Sepharose and Mono S and gel filtration on Superdex 75 by a fast protein liquid chromatography system.

Jack H. Wong; Tzi Bun Ng; Hexiang Wang; Stephen Cho Wing Sze; Kalin Yanbo Zhang; Qi Li; Xiaoxu Lu

2011-01-01

334

In Vitro Interactions between Antifungals and Immunosuppressive Drugs against Zygomycetes ?  

PubMed Central

The in vitro interaction of antifungals with immunosuppressive drugs was evaluated against zygomycetes. The combination of amphotericin B with cyclosporine, rapamycin, or tacrolimus was synergistic for 90%, 70%, and 30% of the isolates, respectively. For posaconazole, itraconazole, and ravuconazole, synergy was more frequently observed with cyclosporine than with rapamycin or tacrolimus and antagonistic interactions were rarely noted. In summary, calcineurin inhibitors and rapamycin can be synergistic in vitro with amphotericin B and azoles against zygomycetes.

Dannaoui, Eric; Schwarz, Patrick; Lortholary, Olivier

2009-01-01

335

Persistence of histoplasma in adrenals 7 years after antifungal therapy.  

PubMed

Adrenal histoplasmosis is an uncommon cause for adrenal insufficiency. The duration of treatment for adrenal histoplasmosis is not clear. Existing treatment regimens advocate antifungals given for periods ranging from 6 months to 2 years. We report here a rare case who showed persistence of histoplasma in adrenal biopsy 7 years after being initially treated with itraconazole for 9 months. This calls for a prolonged therapy with regular review of adrenal morphology and histology in these patients. PMID:23869317

Kothari, Deepak; Chopra, Shweta; Bhardwaj, Minakshi; Ajmani, Ajay K; Kulshreshtha, Bindu

2013-05-01

336

New developments in the antifungal susceptibility testing of Candida  

Microsoft Academic Search

Antifungal susceptibility testing of Candida spp has been standardized and refined and now may play an important role in managing Candida infections. Important new developments include standardizing methods for testing echinocandins, fluconazole, and voriconazole\\u000a and establishing interpretive breakpoints for these agents. Refinements in broth microdilution technology include the ability\\u000a to read results after 24-hour incubation for several agents, addition of

Michael A. Pfaller

2008-01-01

337

Colorimetric Assay for Antifungal Susceptibility Testing of Aspergillus Species  

Microsoft Academic Search

A colorimetric assay for antifungal susceptibility testing of Aspergillus species (Aspergillus fumigatus, Asper- gillus flavus, Aspergillus terreus, Aspergillus nidulans, and Aspergillus ustus) is described based on the reduction of the tetrazolium salt 2,3-bis(2-methoxy-4-nitro-5-((sulphenylamino)carbonyl)-2H-tetrazolium-hydroxide (XTT) in the presence of menadione as an electron-coupling agent. The combination of 200 g of XTT\\/ml with 25 M menadione resulted in a high production of

JOSEPH MELETIADIS; JOHAN W. MOUTON; JACQUES F. G. M. MEIS; BIANCA A. BOUMAN; J. PETER DONNELLY; PAUL E. VERWEIJ

2001-01-01

338

Antifungal Susceptibility Profile of Human-Pathogenic Species of Lichtheimia?  

PubMed Central

Forty-four isolates belonging to human pathogenic species of Lichtheimia were tested against nine antifungal agents by using the EUCAST methodology. No remarkable differences were found between the clinical species, although L. ramosa showed slightly higher MICs for all drugs. Amphotericin B was the most active drug. Among azole drugs, posaconazole had the best activity in vitro and voriconazole was inactive. Echinocandins showed activity for some isolates, suggesting a potential role in combination therapy.

Alastruey-Izquierdo, Ana; Cuesta, Isabel; Walther, Grit; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis

2010-01-01

339

Antifungal activity of Moroccan plants against citrus fruit pathogens  

Microsoft Academic Search

The aim of this study was to find an alternative to the chemical fungicides currently used in the control of postharvest citrus\\u000a fruit diseases. Here we screened twenty-one medicinal and aromatic plants used in southern Moroccan traditional medicine for\\u000a their activity against Penicillium digitatum, Penicillium italicum and Geotrichum candidum. The antifungal efficacy of powders, essential oils and solvent extracts of

N. Ameziane; H. Boubaker; H. Boudyach; F. Msanda; A. Jilal; A. Ait Benaoumar

2007-01-01

340

Interaction of Common Azole Antifungals with P Glycoprotein  

Microsoft Academic Search

Both eucaryotic and procaryotic cells are resistant to a large number of antibiotics because of the activities of export transporters. The most studied transporter in the mammalian ATP-binding cassette transporter superfamily, P glycoprotein (P-gp), ejects many structurally unrelated amphiphilic and lipophilic xenobiotics. Observed clinical interactions and some in vitro studies suggest that azole antifungals may interact with P-gp. Such an

Er-jia Wang; Karen Lew; Christopher N. Casciano; Robert P. Clement; William W. Johnson

2002-01-01

341

ANTIBACTERIAL AND ANTIFUNGAL EFFECTS OF SOFT CONTACT LENS DISINFECTION SOLUTIONS  

Microsoft Academic Search

Absia'act -- A\\/ms: To study the antibacterial and antifungal effects of soft contact lens disinfection solutions. Methods: Eight contact lens disinfection solutions containing hydrogen peroxide or biguanides or polyquad compounds were evaluated with respect to their ability to disinfect a saline solution experimentally contaminated with different bacteria and with a fungus. We used cultures in blood Agar, MueUer-Hinton agar and

Juan Cano-Parra; Inmaculada Bueno-Gimeno; Robert Mont

342

Antioxidant and Antifungal Activity of Verbena officinalis L. Leaves  

Microsoft Academic Search

The scavenging activity against DPPH (1,1-diphenil-2-picrylhydrazyl) radical and the antifungal effect against chloroform,\\u000a ethyl acetate and 50% methanolic extracts of Verbena officinalis leaves were investigated. The activity of different fractions of 50% methanolic extract and some isolated compounds were\\u000a also investigated. The results suggest that 50% methanolic extract and caffeoyl derivatives could potentially be considered\\u000a as excellent and readily available

E. Casanova; J. M. García-Mina; M. I. Calvo

2008-01-01

343

Antifungal activity of Paraguayan plants used in traditional medicine.  

PubMed

The antifungal activity of aqueous, dichloromethane and methanol extracts from 14 Paraguayan plants used in traditional medicine for the treatment of skin diseases was assayed in vitro by the agar disk diffusion method against 11 fungal strains comprising several filamentous fungi and yeasts. Among them, the dichloromethane extracts of Acanthospermum australe, Calycophyllum multiflorum, Geophila repens and Tabebuia avellanedae, as well as the aqueous and methanol extracts of the latter, showed the highest activity. PMID:11378288

Portillo, A; Vila, R; Freixa, B; Adzet, T; Cañigueral, S

2001-06-01

344

Antifungal activity of tuberose absolute and some of its constituents.  

PubMed

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. PMID:16106389

Nidiry, Eugene Sebastian J; Babu, C S Bujji

2005-05-01

345

Mechanism of Action of Efinaconazole, a Novel Triazole Antifungal Agent  

PubMed Central

The mechanism of action of efinaconazole, a new triazole antifungal, was investigated with Trichophyton mentagrophytes and Candida albicans. Efinaconazole dose-dependently decreased ergosterol production and accumulated 4,4-dimethylsterols and 4?-methylsterols at concentrations below its MICs. Efinaconazole induced morphological and ultrastructural changes in T. mentagrophytes hyphae that became more prominent with increasing drug concentrations. In conclusion, the primary mechanism of action of efinaconazole is blockage of ergosterol biosynthesis, presumably through sterol 14?-demethylase inhibition, leading to secondary degenerative changes.

Nagashima, Maria; Shibanushi, Toshiyuki; Iwata, Atsushi; Kangawa, Yumi; Inui, Fumie; Siu, William J. Jo; Pillai, Radhakrishnan; Nishiyama, Yayoi

2013-01-01

346

Novel antifungal defensins from Nigella sativa L. seeds  

Microsoft Academic Search

From seeds of Nigella sativa L. (Ranunculaceae), an endemic plant of Uzbekistan, two novel defensins named Ns-D1 and Ns-D2, were isolated and sequenced. The peptides differ by a single amino acid residue and show high sequence similarity to Raphanus sativus L. defensins Rs-AFP1 and Rs-AFP2. The Ns-D1 and Ns-D2 defensins display strong although divergent antifungal activity towards a number of

Eugene A. Rogozhin; Yulia I. Oshchepkova; Tatyiana I. Odintsova; Natalia V. Khadeeva; Olga N. Veshkurova; Tsezi A. Egorov; Eugene V. Grishin; Shavkat I. Salikhov

2011-01-01

347

Synthesis of diaryl-azo derivatives as potential antifungal agents.  

PubMed

As compared with a commercially available agricultural fungicide hymexazol, some phenyl-azo phenol derivatives (e.g., 4a, 4b, 4f, 4n, 4q, 4u, and 4v) exhibited the more promising and pronounced antifungal activities in vitro against seven phytopathogenic fungi. It seemed that 4-((un)substituted phenylazo)-phenol and 4-((un)substituted phenylazo)-3-methylphenol might be considered as new lead structures for further design of agricultural fungicides. PMID:20570508

Xu, Hui; Zeng, Xiwen

2010-07-15

348

Efficacy of some natural compounds as antifungal agents  

PubMed Central

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.

Vengurlekar, Sudha; Sharma, Rajesh; Trivedi, Piyush

2012-01-01

349

Antifungal defensins and their role in plant defense.  

PubMed

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 ?M 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

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

2014-01-01

350

Phylogenetic relationships matter: antifungal susceptibility among clinically relevant yeasts.  

PubMed

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 1?, 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

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

2014-03-01

351

In vitro effect of antifungal drugs on pathogenic Naegleria spp.  

PubMed

An ameba of the genus Naegleria causing fatal meningoencephalitis in human subjects was investigated for its sensitivity to antifungal drugs: amphotericin B, ketoconazole, fluconazole and itraconazole. The efficacy of these antifungal drugs for pathogenic Naegleria spp was investigated in three strains isolated from patients who had died of primary amebic meningoencephalitis infection at Siriraj Hospital (1986), Ramathibodi Hospital (1987) and Chachoengsao Hospital (1987). All of the isolates were maintained in axenic culture in the Department of Parasitology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand. The sensitivities of the antifungal drugs (MIC50) were: amphotericin B (0.05-0.5 microg/ml), ketoconazole (0.125 microg/ml), fluconazole (0.5-2.0 mg/ml), and itraconazole (10 mg/ml) (p < 0.05). It is important to explain that ketoconazole is slightly more effective than amphotericin B because its action is directed of the permeability of the amebic membrane. The amebae were more resistant ot fluconazole and itraconazole due to the action of the cytochrome P450 multienzyme (in the case of fluconazole) and the direct effect on heme-iron, blocking cytochrome P450-dependent chitin synthesis (in the case of itraconzole). We conclude that amphotericin B and ketoconazole remain the main drugs with proven activity against pathogenic Naegleria spp. PMID:12118457

Tiewcharoen, Supathra; Junnu, Virach; Chinabut, Pisith

2002-03-01

352

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

PubMed

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

Lam, Sze Kwan; Ng, Tzi Bun

2010-05-01

353

Antifungal Therapy and Outcomes in Infants with Invasive Candida Infections  

PubMed Central

Background Invasive candidiasis is a leading cause of mortality and morbidity in neonatal intensive care units. Treatment recommendations are limited by a lack of comparative outcomes data. Methods We identified all infants ?120 days of age with positive blood, urine, or cerebrospinal fluid cultures for Candida sp. who received amphotericin B deoxycholate, fluconazole, amphotericin B lipid products, or combination therapy admitted to 1 of 192 neonatal intensive care units in the United States between 1997 and 2003. Primary outcome measures included overall mortality and therapeutic failure (combined outcome of duration of infection >7 days, need for additional antifungal therapy, or death prior to discharge). We compared outcomes by antifungal therapy using logistic regression, controlling for gestational age, day of life at start of antifungal therapy, delay in therapy, and site of infection. Results Overall, 138/730 (19%) infants died. On multivariable logistic regression, we observed higher overall mortality for infants receiving amphotericin B lipid products compared with infants receiving amphotericin B deoxycholate (OR 1.96 [95% CI: 1.16, 3.33]; p=0.01) or fluconazole (OR 2.39 [1.18, 4.83]; p=0.02). Conclusions Infants treated with amphotericin B lipid products had higher mortality than infants treated with either amphotericin B deoxycholate or fluconazole. This finding may be related to inadequate penetration of amphotericin B lipid products into the kidneys, inappropriate dosing in premature infants, or unknown differences in acuity of illness in infants treated with amphotericin B lipid products.

ASCHER, SIMON B.; SMITH, P. BRIAN; WATT, KEVIN; BENJAMIN, DANIEL K.; COHEN-WOLKOWIEZ, MICHAEL; CLARK, REESE H.; BENJAMIN, DANIEL K.; MORAN, CASSANDRA

2012-01-01

354

Antifungal Properties of Chenopodium ambrosioides Essential Oil Against Candida Species  

PubMed Central

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 ?-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.

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

2010-01-01

355

In vitro antifungal properties of mouthrinses containing antimicrobial agents.  

PubMed

The purpose of this study was to investigate the in vitro antifungal properties of seven commercial mouthrinses containing antimicrobial agents. These included cetylpyridinium chloride (CPC), chlorhexidine digluconate (CHX), hexetidine (HEX), sanguinarine (SNG), and triclosan (TRN). The minimum fungicidal concentration (MFC) against six species of yeasts was determined by a broth macrodilution method. The kill-time of mouthrinses at half the concentration of the commercial formulations was also determined. MFCs were achieved with each mouthrinse, except the SNG-containing mouthrinse, against all the organisms being tested. However, the CPC-containing mouthrinse appeared more active than the other products (P < 0.001). There were no significant differences in MFC values among CHX mouthrinse products, once adjusted for initial concentration differences (P = 0.1). Kill-times of mouthrinses containing either CHX or CPC were less than or equal to 180 seconds with all the species of yeasts, and no significant differences were found among these products (P = 0.18). On the other hand, mouthrinses containing either TRN or HEX did not show a lethal effect on Candida albicans, Candida parapsilosis, or Candida guilliermondii. No kill-times were achieved with the SNG-containing mouthrinse. These results suggest that mouthrinses containing antimicrobial agents might represent an appropriate alternative to conventional antifungal drugs in the management of oral candidiasis. However, the effectiveness of antimicrobial mouthrinses as antifungal agents needs to be evaluated in further clinical trials. PMID:9287062

Giuliana, G; Pizzo, G; Milici, M E; Musotto, G C; Giangreco, R

1997-08-01

356

Antifungal prophylaxis in pediatric lung transplantation: An international multicenter survey.  

PubMed

Fungal infections create a significant risk to pediatric lung transplant recipients. However, no international consensus guidelines exist for fungal infection prevention strategies. It was the aim to describe the current strategies of antifungal prophylaxis in pediatric lung transplant centers. A self-administered, web-based survey on current practices to prevent fungal infection was circulated to centers within the IPLTC. Twenty-one (88%) IPLTC centers participated, predominantly from Europe and the US. More than 50% of respondents perform adult and pediatric lung transplant operations. Twenty-four percent use universal prophylaxis, 28% give prophylaxis to all patients but stratify the antifungal coverage based on pretransplant risk, and 48% target prophylaxis to only the children with CF or pretransplantation fungal colonization. Commonly, centers aim to target Aspergillus and Candida infection. Monotherapy with either voriconazole or inhaled amphotericin B is used in the majority of centers. Institutions utilize prophylactic therapy for variable time periods (40% 3-6 months; 30% ?12 months). Alternative drugs were prescribed for lack of tolerance, toxicity, or positive surveillance culture. TDM (itraconazole/voriconazole) was used in 86% of centers. The survey revealed a wide range of antifungal prophylaxis strategies as current international practice in pediatric lung transplant recipients. PMID:24802346

Mead, Lee; Danziger-Isakov, Lara A; Michaels, Marian G; Goldfarb, Samuel; Glanville, Allan R; Benden, Christian

2014-06-01

357

Supramolecular high-aspect ratio assemblies with strong antifungal activity.  

PubMed

Efficient and pathogen-specific antifungal agents are required to mitigate drug resistance problems. Here we present cationic small molecules that exhibit excellent microbial selectivity with minimal host toxicity. Unlike typical cationic polymers possessing molecular weight distributions, these compounds have an absolute molecular weight aiding in isolation and characterization. However, their specific molecular recognition motif (terephthalamide-bisurea) facilitates spontaneous supramolecular self-assembly manifesting in several polymer-like properties. Computational modelling of the terephthalamide-bisurea structures predicts zig-zag or bent arrangements where distal benzyl urea groups stabilize the high-aspect ratio aqueous supramolecular assemblies. These nanostructures are confirmed by transmission electron microscopy and atomic force microscopy. Antifungal activity against drug-sensitive and drug-resistant strains with in vitro and in vivo biocompatibility is observed. Additionally, despite repeated sub-lethal exposures, drug resistance is not induced. Comparison with clinically used amphotericin B shows similar antifungal behaviour without any significant toxicity in a C. albicans biofilm-induced mouse keratitis model. PMID:24316819

Fukushima, Kazuki; Liu, Shaoqiong; Wu, Hong; Engler, Amanda C; Coady, Daniel J; Maune, Hareem; Pitera, Jed; Nelson, Alshakim; Wiradharma, Nikken; Venkataraman, Shrinivas; Huang, Yuan; Fan, Weimin; Ying, Jackie Y; Yang, Yi Yan; Hedrick, James L

2013-01-01

358

Benzofurazan derivatives as antifungal agents against phytopathogenic fungi.  

PubMed

A series of benzofurazan derivatives were prepared and evaluated for their biological activities against four important phytopathogenic fungi, namely, Rhizoctonia solani, Sclerotinia sclerotiorum, Fusarium graminearum and Phytophthora capsici, using the mycelium growth inhibition method. The structures of these compounds were characterized by (1)H NMR, (13)C NMR, and HRMS. N-(3-chloro-4-fluorophenyl)-7-nitrobenzo[c][1,2,5]oxadiazol-4-amine (A3) displayed the maximum antifungal activity against R. solani (IC50 = 1.91 ?g/mL), which is close to that of the positive control Carbendazim (IC50 = 1.42 ?g/mL). For other benzofurazan derivatives with nitro group at R(4) position (A series), 9 out of 30 compounds exhibited high antifungal effect against strain R. solani, with IC50 values less than 5 ?g/mL. Most of the derivatives with substituents at R(2) and R(3) positions (B series) displayed moderate growth inhibition against S. sclerotiorum (IC50 < 25 ?g/mL). Also, several benzofuran derivatives with nitro group at R(4) position and another conjugated aromatic ring at the R(1) position of the phenyl ring displayed high antifungal capability against strain R. solani. Compounds with substituents at R(2) and R(3) position had moderate efficacy against strain S. sclerotiorum. PMID:24813881

Wang, Lili; Zhang, Ying-Ying; Wang, Lei; Liu, Feng-You; Cao, Ling-Ling; Yang, Jing; Qiao, Chunhua; Ye, Yonghao

2014-06-10

359

Antifungal activities and chemical composition of some medicinal plants.  

PubMed

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

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

2014-06-01

360

Antifungal defensins and their role in plant defense  

PubMed Central

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 ?M 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.

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

2014-01-01

361

Flow Cytometry Susceptibility Testing for the Antifungal Caspofungin  

PubMed Central

Rapid antifungal susceptibility testing for the antifungal agent caspofungin can be performed using flow cytometry (FC). An FC procedure using acridine orange provided minimum inhibitory concentration (MIC) results within 7 to 9 h which were compared with results obtained using the NCCLS M27-A2 protocol. To evaluate the consistency of this method, susceptibility testing using caspofungin was performed using 73 isolates of eight different species of Candida from various clinical samples in Central California. Macrotiter or microdilution tests were performed according to the NCCLS M27-A2 protocol, and the MICs were compared to those provided by our flow cytometry method. All isolates tested had results within the sensitive interpretive category, and 90% of the results compared within 1 dilution, showing excellent agreement between the methods. The MIC at which 50% of the isolates tested were inhibited (MIC50) and the MIC90 of caspofungin for all eight Candida species were within 1 dilution. This flow cytometer 7-h protocol for testing the antifungal susceptibility of Candida species to caspofungin provided results equivalent to those obtained with the M27-A2 protocol.

Mitchell, M.; Hudspeth, M.; Wright, A.

2005-01-01

362

Pothomorphe umbellata: antifungal activity against strains of Trichophyton rubrum.  

PubMed

Trichophyton rubrum is a dermatophyte, which can cause infections in human skin, hair and nail. Pothomorphe umbellata (L.) Miq. (Piperaceae) is a native Brazilian plant, in which phytochemical studies have demonstrated the presence of steroids, 4-nerolidylcatechol, sesquiterpenes and essential oils. The objective of this study was to analyze the in vitro activity of extracts and fractions of P. umbellata on resistant strains of T. rubrum. The microdilution plate method was utilized to test Tr1, H6 and ?TruMDR2 strains of T. rubrum; ?TruMDR2 strain was obtained from H6 by TruMDR2 gene rupture, which is involved in multiple drugs resistance. The highest antifungal activity to all strains was observed for dichloromethane and hexane fractions of the 70% ethanolic extract which showed minimal inhibitory concentration (MIC) and minimal fungicide concentration (MFC) of 78.13 ?g/mL. This antifungal activity was also obtained by 70% ethanolic extract, which presented MIC and MFC of 78.13 ?g/mL to ?TruMDR2, whereas the MIC values for Tr1 and H6 were 78.13 and 156.25 ?g/mL, respectively. Our results suggest the potential for future development of new antifungal drugs from P. umbellata, especially to strains presenting multiple resistance. PMID:23518086

Rodrigues, E R; Nogueira, N G P; Zocolo, G J; Leite, F S; Januario, A H; Fusco-Almeida, A M; Fachin, A L; de Marchi, M R R; dos Santos, A G; Pietro, R C L R

2012-09-01

363

Sensitivity of some strains of the genus Epidermophyton to different antifungal agents.  

PubMed

The inhibitory activity of some antifungal agents against 17 strains of genus Epidermophyton have been studied. The behaviour of Epidermophyton stockdaleae against antifungal agents tested is clearly different from that observed in the strains belonging to Epidermophyton floccosum, since all of the latter were sensitive to the antifungal agents used and the geophilic species showed resistance to griseofulvin, isoconazole, natamycin and nystatin, and intermediate sensitivity to ketoconazole and miconazole. The low sensitivity of E. stockdaleae (and other geophilic dermatophytes) to antifungal agents could be a problem in the current therapy if further studies or case reports demonstrate their pathogenic role. PMID:2788246

Cabañes, F J; Abarca, L; Bragulat, M; Bruguera, T

1989-03-01

364

Impact of Absolute Stereochemistry on the Antiangiogenic and Antifungal Activities of Itraconazole  

PubMed Central

Itraconazole is used clinically as an antifungal agent and has recently been shown to possess antiangiogenic acitivity. Itraconazole has three chiral centers that give rise to eight stereoisomers. The complete role of stereochemistry in the two activities of itraconazole, however, has not been addressed adequately. For the first time, all eight stereoisomers of itraconazole (1a–1h) have been synthesized and evaluated for activity against human endothelial cell proliferation and for antifungal activity against five fungal strains. Distinct antiangiogenic and antifungal activity profiles of the trans- stereoisomers, especially 1e and 1f, suggest different molecular mechanisms underlying the anti-angiogenic and anti-fungal activities of itraconazole.

Shi, Wei; Nacev, Benjamin A.; Bhat, Shridhar; Liu, Jun O.

2011-01-01

365

Synthesis, in vitro antifungal evaluation and in silico study of 3-azolyl-4-chromanone phenylhydrazones  

PubMed Central

Background The currently available antifungal drugs suffer from toxicity, greatest potential drug interactions with other drugs, insufficient pharmacokinetics properties, and development of resistance. Thus, development of new antifungal agents with optimum pharmacokinetics and less toxicity is urgent task. In the search for new azole antifungals, we have been previously described azolylchromanone oxime ethers as rigid analogs of oxiconazole. In continuation of our work, we incorporated phenylhydrazone moiety instead of oxime ether fragment in azolylchromanone derivatives. Methods The 3-azolyl-4-chromanone phenylhydrazones were synthesized via ring closure of 2-azolyl-2'-hydroxyacetophenones and subsequent reaction with phenylhydrazine. The biological activity of title compounds was evaluated against different pathogenic fungi including Candida albicans, Saccharomyces cerevisiae, Aspergillus niger, and Microsporum gypseum. Docking study, in silico toxicity risks and drug-likeness predictions were used to better define of title compounds as antifungal agents. Results The in vitro antifungal activity of compounds based on MIC values revealed that all compounds showed good antifungal activity against C. albicans, S. cerevisiae and M. gypseum at concentrations less than 16 ?g/mL. Among the test compounds, 2-methyl-3-imidazolyl derivative 3b showed the highest values of drug-likeness and drug-score. Conclusion The 3-azolyl-4-chromanone phenylhydrazones considered as analogs of 3-azolyl-4-chromanone oxime ethers basically designed as antifungal agents. The antifungal activity of title compounds was comparable to that of standard drug fluconazole. The drug-likeness data of synthesized compounds make them promising leads for future development of antifungal agents.

2012-01-01

366

Novel carboline derivatives as potent antifungal lead compounds: design, synthesis, and biological evaluation.  

PubMed

A series of novel antifungal carboline derivatives was designed and synthesized, which showed broad-spectrum antifungal activity. Particularly, compound C38 showed comparable in vitro antifungal activity to fluconazole without toxicity to human embryonic lung cells. It also exhibited good fungicidal activity against both fluconazole-sensitive and -resistant Candida albicans cells and had potent inhibition activity against Candida albicans biofilm formation and hyphal growth. Moreover, C38 showed good synergistic antifungal activity in combination with fluconazole (FLC) against FLC-resistant Candida species. Preliminary mechanism studies revealed that C38 might act by inhibiting the synthesis of fungal cell wall. PMID:24900870

Wang, Shengzheng; Wang, Yan; Liu, Wei; Liu, Na; Zhang, Yongqiang; Dong, Guoqiang; Liu, Yang; Li, Zhengang; He, Xiaomeng; Miao, Zhenyuan; Yao, Jianzhong; Li, Jian; Zhang, Wannian; Sheng, Chunquan

2014-05-01

367

The role of primary antifungal prophylaxis in patients with haematological malignancies.  

PubMed

Invasive fungal infections (IFIs) represent important complications in patients with haematological malignancies. Chemoprevention of IFIs may play an important role in this setting, but in the past decades the majority of antifungal drugs utilized demonstrated poor efficacy, particularly in the prevention of invasive aspergillosis. The new triazoles are very useful antifungal drugs, more suitable for prophylaxis of IFIs than amphotericin B and echinocandins. In this review, the main clinical data about antifungal prophylaxis with fluconazole, itraconazole, voriconazole and posaconazole are analysed. At present, posaconazole appears to be the most efficacious azole in antifungal prophylaxis, particularly in patients with acute myeloid leukaemia. PMID:24372659

Pagano, L; Caira, M

2014-06-01

368

A technique for detecting antifungal activity of proteins separated by polyacrylamide gel electrophoresis.  

PubMed

A technique was developed for the detection of antifungal activity of proteins after discontinuous polyacrylamide gel electrophoresis under native conditions. The antifungal activity is detected as growth inhibition zones in a homogeneous fungal lawn, grown in an agar layer spread on top of the polyacrylamide gel. The position of proteins with antifungal activity can be determined on a diffusion blot prepared from the same gel. The technique is illustrated for three antifungal plant proteins, i.e. alpha-purothionin, Urtica dioica agglutinin, and tobacco chitinase. PMID:1889394

De Bolle, M F; Goderis, I J; Terras, F R; Cammue, B P; Broekaert, W F

1991-06-01

369

Combination of fluconazole with non-antifungal agents: A promising approach to cope with resistant Candida albicans infections and insight into new antifungal agent discovery.  

PubMed

The past decades have witnessed a dramatic increase in invasive fungal infections, especially candidiasis. Despite the development of more effective new antifungal agents, fluconazole (FLC) is still widely used in the clinic because of its efficacy and low toxicity. However, as the number of patients treated with FLC has increased, FLC-resistant Candida albicans isolates emerge more frequently. In addition, biofilm-associated infections are commonly encountered and their resistance poses a great challenge to antifungal treatment. Various approaches have been proposed to increase the susceptibility of C. albicans to FLC in order to cope with treatment failures, among which is the combination of FLC with different classes of non-antifungal agents such as antibacterials, calcineurin inhibitors, heat shock protein 90 inhibitors, calcium homeostasis regulators and traditional Chinese medicine drugs. Interestingly, many of these combinations showed synergistic effects against C. albicans, especially resistant strains. The main mechanisms of these synergistic effects appear to be increasing the permeability of the membrane, reducing the efflux of antifungal drugs, interfering with intracellular ion homeostasis, inhibiting the activity of proteins and enzymes required for fungal survival, and inhibiting biofilm formation. These modes of action and the antifungal mechanisms of various compounds referenced in this paper highlight the idea that the reversal of fungal resistance can be achieved through various mechanisms. Studies examining drug interactions will hopefully provide new approaches against antifungal drug resistance as well as insight into antifungal agent discovery. PMID:24503221

Liu, Shuyuan; Hou, Yinglong; Chen, Xu; Gao, Yuan; Li, Hui; Sun, Shujuan

2014-05-01

370

Econazole: a review of its antifungal activity and therapeutic efficacy.  

PubMed

Econazole1 is a recently introduced imidazole antifungal agent which is very closely related structurally to another imidazole derivative, miconazole. For local application the nitrate salt of econazole is used, while in preliminary investigations of systemic use in a few patients econazole base has been administered orally or intravenously. In uncontrolled studies in large numbers of patients, econazole nitrate has been administered topically in the treatment of dermatomycoses due to a wide variety of fungi, and vaginally in the treatment of vaginal candidosis; but it has not been compared with any other antifungal drug in controlled therapeutic trials in mycoses of the skin and has only been compared with nystatin in a few patients with vaginal candidosis. Until adequate comparative studies are done the relative place of econazole in the treatment of dermatomycoses and vaginal condidosis, compared with traditional antifungal agents and with other imidazole derivatives such as miconazole or clotrimazole, cannot be clearly stated. Nevertheless, econazole nitrate is an effective antifungal drug. In dermatological studies about 90% of a large number of patients were cured, often after a relatively short treatment period (2 to 6 weeks, as occurs with other imidazole antifungal agents). The cure rate was only slightly lower (about 85%) in patients with severe mycoses of many years' duration than in those whose infections were of more recent onset. In vaginal candidosis a 3-day treatment regimen using a 150mg suppository once daily was only slightly less effective (85% mycological cure rate) than a 15-day regimen using a 50mg dose (suppository or cream) once daily (90% cure rate). A 3 to 5 day 'higher' dose regimen was slightly more effective than a standard 15-day regimen of nystatin vaginal inserts in a small group of patients with vaginal candidosis. The convenience of the higher-dose shorter term regimen would likely be an important advantage to most patients. Whether other agents useful in vaginal candidosis would be as effective as econazole were they to be used in this way, has not been determined. Topical or intravaginal econazole nitrate has usually been well tolerated, side effects being limited to local irritation in about 1 to 4% of patients in most studies. PMID:98315

Heel, R C; Brogden, R N; Speight, T M; Avery, G S

1978-09-01

371

Glycosidic activities of Candida albicans after action of vegetable latex saps (natural antifungals) and isoconazole (synthetic antifungal).  

PubMed

Glycosidic activities have been examined in Candida albicans grown on medium culture containing latex sap (natural antifungal) or isoconazole (synthetic antifungal). The different types of utilized latex sap were those of Lactuca sativa (latex exuded from articulated laticifers) and Asclepias curassavica (latex flowing from non-articulated laticifers). The same enzyme assays were performed on C. albicans grown without antifungal compounds. Except for alpha-arabinosidase, all glycosidase activities were increased when C. albicans was grown in medium supplemented with L. sativa latex sap. The most stimulated activities were those of beta-fucosidase, alpha-galactosidase, alpha- and beta-glucosidase, alpha- and beta-mannosidase, acetyl-beta-glucosaminidase. The presence of A. curassavica latex sap in culture medium produced similar results: the most stimulated activities were those of alpha-mannosidase, alpha-galactosidase, acetyl-beta-glucosaminidase and beta-fucosidase. Electron microscope observations suggested a correlation between this stimulation of glycosidic activities and the fungal cell wall breakdown. For comparison the presence of isoconazole in culture medium yields no increase in glycosidic activities and no ultrastructural modification of fungal cell wall. The mode of action of latex saps in cell wall breakdown is discussed. PMID:1922192

Giordani, R; Moulin-Traffort, J; Régli, P

1991-01-01

372

Antifungal prophylaxis in hematopoietic stem cell transplant recipients: the unfinished tale of imperfect success  

Microsoft Academic Search

Antifungal prophylaxis in hematopoietic stem cell transplant recipients is a rapidly evolving field. For this prophylaxis to be beneficial and cost-effective, the risk of a life-threatening invasive fungal infection (IFI) should outweigh the risks of toxic effects and drug interactions introduced by the antifungal agent used. Not all hematopoietic stem cell transplant recipients have the same risk of IFIs. New

D P Kontoyiannis

2011-01-01

373

Antifungal activity of plant extracts against Arthrinium sacchari and Chaetomium funicola  

Microsoft Academic Search

Various plant extracts were examined for antifungal activity with the objective of improving the commercial sterility of aseptically filled tea beverage products in PET bottles. When the hot water extract and the methanol extract of 29 samples were measured for their antifungal activity against Arthrinium sacchari M001 and Chaetomium funicola M002 strains, five samples, Acer nikoense, Glycyrrhiza glabra, Lagerstroemia speciosa,

Jun Sato; Keiichi Goto; Fumio Nanjo; Shigeyuki Kawai; Kousaku Murata

2000-01-01

374

Antifungal Activities of Hedychium Essential Oils and Plant Extracts Against Mycotoxigenic Fungi  

Microsoft Academic Search

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 fungi, Aspergillus flavus and Fusarium verticillioides, that produce two major classes of mycotoxins, aflatoxin, and fumonisin, respectively, on

Kanniah Rajasekaran; Hamidou F. Sakhanokho; Nurhayat Tabanca

2012-01-01

375

Evaluation of Etest for Direct Antifungal Susceptibility Testing of Yeasts in Positive Blood Cultures  

Microsoft Academic Search

The performance of the Etest (AB BIODISK, Solna, Sweden) for direct antifungal susceptibility testing of yeasts in positive blood cultures was compared with that of the macrodilution method for determining the MICs of five antifungal agents. Culture broths with blood from bottles positive for yeasts were inoculated directly onto plates for susceptibility testing with the Etest, and the MICs were

HSEIN CHANG CHANG; JUI JUNG CHANG; SHIH HUANG CHAN; AY HUEY HUANG; TSU LAN WU; MIAO CHU LIN

2001-01-01

376

In vitro antifungal susceptibility of clinical isolates of Arthrographis kalrae, a poorly known opportunistic fungus.  

PubMed

The in vitro antifungal activity of amphotericin B (AMB), itraconazole, voriconazole, posaconazole, terbinafine (TRB), caspofungin, anidulafungin and micafungin were evaluated by a broth microdilution technique against 22 isolates of Arthrographis kalrae of clinical origin. TRB showed the highest activity, followed by the azoles, particularly posaconazole. AMB exerted low activity whereas the echinocandins showed almost no antifungal activity. PMID:24147779

Sandoval-Denis, Marcelo; Giraldo, Alejandra; Sutton, Deanna A; Fothergill, Annette W; Guarro, Josep

2014-04-01

377

Activity of the Triazole Antifungal R126638 as Assessed by Corneofungimetry  

Microsoft Academic Search

Background: R126638 is a novel triazole exhibiting potent in vitro and in vivo antifungal activity against fungal pathogens including dermatophytes and yeasts. Objective: To determine the antifungal activity in time in the stratum corneum of healthy volunteers after oral intake of R126638 at a daily dose of 100 or 200 mg for 1 week. Method: Sixteen male volunteers were randomly

C. Piérard-Franchimont; J. Ausma; L. Wouters; V. Vroome; L. Vandeplassche; M. Borgers; G. Cauwenbergh; G. E. Piérard

2006-01-01

378

Risk of Fungemia Due to Rhodotorula and Antifungal Susceptibility Testing of Rhodotorula Isolates  

PubMed Central

Rhodotorula infections occur among patients with immunosuppression and/or central venous catheters. Using standardized methods (NCCLS M27-A), we determined the antifungal susceptibilities of 10 Rhodotorula bloodstream infection isolates. Patient information was collected for clinical correlation. The MICs of amphotericin B and posaconazole were the lowest, and the MICs of triazoles and echinocandins were higher than those of other antifungal agents.

Zaas, Aimee K.; Boyce, Molly; Schell, Wiley; Lodge, Barbara Alexander; Miller, Jackie L.; Perfect, John R.

2003-01-01

379

[Bio-guided isolation of an antifungal from Haliclona enamela collected from Jorf Lasfar port, Morocco].  

PubMed

In the context of our search for new biologically active secondary metabolites from marine invertebrates, we have isolated an antifungal from Haliclona enamela collected from Jorf Lasfar Port, El Jadida, Morocco. This has a strong antifungal activity against three yeasts (two Candida spp. and one Cryptococcus spp.) involved in human mycology and especially against Candida tropicalis resistant to nystatin and amphotericin B. PMID:23726234

El-Wahidi, M; El-Amraoui, B; Fassouane, A; Bamhaoud, T

2013-06-01

380

Phase-dependent antifungal activity against Aspergillus fumigatus developing multicellular filamentous biofilms  

Microsoft Academic Search

Objectives: Aspergillus fumigatus undergoes morphological transition throughout its growth and development. These changes have direct implications for the effectiveness of antifungal treatment. Here we report the in vitro antifungal activity of voriconazole, amphotericin B and caspofungin against three specific phases of multicellular development of A. fumigatus. Methods: A. fumigatus conidia were propagated for 8, 12 and 24 h prior to

Eilidh Mowat; Sue Lang; Craig Williams; Elaine McCulloch; Brian Jones; Gordon Ramage

381

Efficacy and safety of topical antifungals in the treatment of dermatomycosis: a systematic review.  

PubMed

The analysis of comparative efficacy and safety of topical antifungals in the literature is restricted to the treatment of tinea pedis and onychomycosis. Therefore our objective was to evaluate and compare the efficacy and safety of topical antifungals used in the treatment of dermatomycosis, we performed a comprehensive search for randomized controlled trials (RCTs) in the following databases: Medline, Cochrane Central Register of Controlled Trials, EMBASE, Lilacs and International Pharmaceutical Abstracts, we identified studies that compared the use of topical antifungals with other antifungals or with placebo published up to July 2010 in English, Spanish or Portuguese. The quality of reporting was assessed according to the Jadad scale; only studies with a score of 3 or more were included. The outcomes evaluated were mycological cure at the end of treatment, sustained cure, occurrence of adverse events and tolerability, including withdrawals due to adverse events. A total of 104 RCTs satisfied the inclusion criteria, containing a total of 135 comparisons, with 55 out of 120 possible comparisons among the 16 drugs evaluated. Pooled data on efficacy showed that all the antifungals were better than placebo. There were no significant differences among antifungal classes. No differences were found in safety or tolerability in any direct comparison. Sensitivity analysis indicated the robustness of the findings. Our results indicate the clear superiority of topical antifungals over placebo but that there is no consistent difference among classes. Mixed treatment comparisons are necessary to rank antifungals, as direct comparisons among many of them are lacking. PMID:22233283

Rotta, I; Sanchez, A; Gonçalves, P R; Otuki, M F; Correr, C J

2012-05-01

382

Discovery of a Novel Broad-Spectrum Antifungal Agent Derived from Albaconazole  

PubMed Central

Synthesis of a strict structural analogue of albaconazole in which the quinazolinone ring is fused by a thiazole moiety led to the discovery of a new triazole with broad-spectrum antifungal activity. Compound I exhibited high in vitro activity against pathogenic Candida species and filamentous fungi and showed preliminary in vivo antifungal efficacy in a mice model of systemic candidiasis.

2013-01-01

383

Purification and characterization of antifungal compounds from Lactobacillus plantarum HD1 isolated from kimchi.  

PubMed

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. PMID:24750809

Ryu, Eun Hye; Yang, Eun Ju; Woo, Eun Rhan; Chang, Hae Choon

2014-08-01

384

Composition of in vitro denture plaque biofilms and susceptibility to antifungals  

Microsoft Academic Search

The aim of this study was to investigate the composition of microcosm denture plaque biofilms and the susceptibility of Candida spp. within these biofilms to antifungal agents. An in vitro model was employed to grow oral biofilms derived from denture associated stomatitis (DAS) patient samples to assess fungal growth in the presence and absence of antifungal agents. The compositions of

Hanadi Lamfon; Zubaida Al-Karaawi; Michael McCullough; Stephen R. Porter; Jonathan Pratten

2005-01-01

385

In vitro Antifungal Activity of Thai Herb and Spice Extracts against Food Spoilage Fungi  

Microsoft Academic Search

The screening of Thai herbs and spices was carried out to investigate their in vitro antifungal activity against Aspergillus niger, A. oryzaeand Penicilliumsp. by using agar well diffusion method. Of thirteen plants tested, crude ethanol extracts of three, namely Piper betel, Boesenbergia pandurata, Andrographis paniculata exhibited antifungal activity against all test microorganisms. Penicillium sp. was more resistant to the extracts

Penkhae Wanchaitanawong; Piyamat Chaungwanit; Ngamtip Poovarodom; Sunee Nitisinprasert

386

Latest developments in assessing antifungal activity using TLC-bioautography: a review.  

PubMed

This paper reviews the use of TLC-bioautography in the search for antifungal compounds from natural sources. The main methods used for antifungal screening are presented, with special emphasis on bioautography. Different aspects of the technique, including the latest chromatographic developments such as HPTLC and HPLC microfractionation are presented. The present status and recent advances made in antifungal bioautography are discussed, and a comprehensive review of the applications over the last 6 years is presented. Various strategies applied in the search for antifungal compounds from natural sources are discussed, with a highlight on the challenges faced when screening complex crude mixtures. The activities of approximately 100 antifungal compounds of natural origin are presented with their minimum inhibitory quantity. The most active natural source compounds against Candida, Cladosporium, Colletotrichum, and Fusarium species are highlighted, and the compound activities discussed. In addition, perspectives concerning future improvements in bioautography sensitivity and reproducibility are noted. PMID:24645492

Favre-Godal, Quentin; Queiroz, Emerson Ferreira; Wolfender, Jean-Luc

2013-01-01

387

Production and Characterization of Antifungal Compounds Produced by Lactobacillus plantarum IMAU10014  

PubMed Central

Lactobacillus plantarum IMAU10014 was isolated from koumiss that produces a broad spectrum of antifungal compounds, all of which were active against plant pathogenic fungi in an agar plate assay. Two major antifungal compounds were extracted from the cell-free supernatant broth of L. plantarum IMAU10014. 3-phenyllactic acid and Benzeneacetic acid, 2-propenyl ester were carried out by HPLC, LC-MS, GC-MS, NMR analysis. It is the first report that lactic acid bacteria produce antifungal Benzeneacetic acid, 2-propenyl ester. Of these, the antifungal products also have a broad spectrum of antifungal activity, namely against Botrytis cinerea, Glomerella cingulate, Phytophthora drechsleri Tucker, Penicillium citrinum, Penicillium digitatum and Fusarium oxysporum, which was identified by the overlay and well-diffusion assay. F. oxysporum, P. citrinum and P. drechsleri Tucker were the most sensitive among molds.

Wang, HaiKuan; Yan, YanHua; Wang, JiaMing; Zhang, HePing; Qi, Wei

2012-01-01

388

A radish seed antifungal peptide with a high amyloid fibril-forming propensity.  

PubMed

The amyloid fibril-forming ability of two closely related antifungal and antimicrobial peptides derived from plant defensin proteins has been investigated. As assessed by sequence analysis, thioflavin T binding, transmission electron microscopy, atomic force microscopy and X-ray fiber diffraction, a 19 amino acid fragment from the C-terminal region of Raphanus sativus antifungal protein, known as RsAFP-19, is highly amyloidogenic. Further, its fibrillar morphology can be altered by externally controlled conditions. Freezing and thawing led to amyloid fibril formation which was accompanied by loss of RsAFP-19 antifungal activity. A second, closely related antifungal peptide displayed no fibril-forming capacity. It is concluded that while fibril formation is not associated with the antifungal properties of these peptides, the peptide RsAFP-19 is of potential use as a controllable, highly amyloidogenic small peptide for investigating the structure of amyloid fibrils and their mechanism of formation. PMID:23665069

Garvey, Megan; Meehan, Sarah; Gras, Sally L; Schirra, Horst J; Craik, David J; Van der Weerden, Nicole L; Anderson, Marilyn A; Gerrard, Juliet A; Carver, John A

2013-08-01

389

Heterologous expression of new antifungal chitinase from wheat.  

PubMed

Chitinases (EC 3.2.1.14) have been grouped into seven classes (class I-VII) on the basis of their structural properties. Chitinases expressed during plant-microbe interaction are involved in defense responses of host plant against pathogens. In the present investigation, chitinase gene from wheat has been subcloned and overexpressed in Escherichia coli BL-21 (DE3). Molecular phylogeny analyses of wheat chitinase indicated that it belongs to an acidic form of class VII chitinase (glycosyl hydrolase family 19) and shows 77% identity with other wheat chitinase of class IV and low level identity to other plant chitinases. The three-dimensional structural model of wheat chitinase showed the presence of 10 alpha-helices, 3 beta-strands, 21 loop turns and the presence of 6 cysteine residues that are responsible for the formation of 3 disulphide bridges. The active site residues (Glu94 and Glu103) may be suggested for its antifungal activity. Expression of chitinase (33 kDa) was confirmed by SDS-PAGE and Western hybridization analyses. The yield of purified chitinase was 20 mg/L with chitinase activity of 1.9 U/mg. Purified chitinase exerted a broad-spectrum antifungal activity against Colletotrichum falcatum (red rot of sugarcane) Pestalotia theae (leaf spot of tea), Rhizoctonia solani (sheath blight of rice), Sarocladium oryzae (sheath rot of rice) Alternaria sp. (grain discoloration of rice) and Fusarium sp. (scab of rye). Due to its innate antifungal potential wheat chitinase can be used to enhance fungal-resistance in crop plants. PMID:17697785

Singh, Arpita; Kirubakaran, S Isaac; Sakthivel, N

2007-11-01

390

Antifungal activity of gold nanoparticles prepared by solvothermal method  

SciTech Connect

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.

Ahmad, Tokeer, E-mail: tahmad3@jmi.ac.in [Nanochemistry Laboratory, Department of Chemistry, Jamia Millia Islamia, New Delhi 110025 (India)] [Nanochemistry Laboratory, Department of Chemistry, Jamia Millia Islamia, New Delhi 110025 (India); Wani, Irshad A.; Lone, Irfan H.; Ganguly, Aparna [Nanochemistry Laboratory, Department of Chemistry, Jamia Millia Islamia, New Delhi 110025 (India)] [Nanochemistry Laboratory, Department of Chemistry, Jamia Millia Islamia, New Delhi 110025 (India); Manzoor, Nikhat; Ahmad, Aijaz [Department of Biosciences, Jamia Millia Islamia, New Delhi 110025 (India)] [Department of Biosciences, Jamia Millia Islamia, New Delhi 110025 (India); Ahmed, Jahangeer [Department of Chemistry, Michigan State University, East Lansing, MI 48824 (United States)] [Department of Chemistry, Michigan State University, East Lansing, MI 48824 (United States); Al-Shihri, Ayed S. [Department of Chemistry, Faculty of Science, King Khalid University, Abha 61413, P.O. Box 9004 (Saudi Arabia)] [Department of Chemistry, Faculty of Science, King Khalid University, Abha 61413, P.O. Box 9004 (Saudi Arabia)

2013-01-15

391

Clinical evaluation of a dried commercially prepared microdilution panel for antifungal susceptibility testing of five antifungal agents against Candida spp. and Cryptococcus neoformans  

Microsoft Academic Search

A commercially prepared dried-broth microdilution panel (Sensititre, TREK Diagnostic Systems, Cleveland, OH) was compared with a reference frozen-broth microdilution panel for antifungal susceptibility testing of 728 clinical isolates of Candida spp. and 98 clinical isolates of Cryptococcus neoformans. The antifungal agents tested were amphotericin B, fluconazole, 5-fluorocytosine (5FC), itraconazole, and voriconazole. Microdilution testing was performed according to NCCLS recommendations. Minimum

M. A. Pfaller; L. Boyken; R. J. Hollis; S. A. Messer; S. Tendolkar; D. J. Diekema

2004-01-01

392

In Vitro Antibacterial and Antifungal Activity of Salicylanilide Benzoates  

PubMed Central

The resistance to antimicrobial agents brings a need of novel antimicrobial agents. We have synthesized and found the in vitro antibacterial activity of salicylanilide esters with benzoic acid (2-(phenylcarbamoyl)phenyl benzoates) in micromolar range. They were evaluated in vitro for the activity against eight fungal and eight bacterial species. All derivatives showed a significant antibacterial activity against Gram-positive strains with minimum inhibitory concentrations ?0.98??mol/L including methicillin-resistant Staphylococcus aureus strain. The most active compounds were 5-chloro-2-(3,4-dichlorophenylcarbamoyl)phenyl benzoate and 4-chloro-2-(4-(trifluoromethyl)phenylcarbamoyl)phenyl benzoate. The antifungal activity is significantly lower.

Kratky, Martin; Vinsova, Jarmila; Buchta, Vladimir

2012-01-01

393

Production of Chlorflavonin, an Antifungal Metabolite of Aspergillus candidus  

PubMed Central

Production of chlorflavonin, a new antifungal antibiotic, by strains of Aspergillus candidus is described. Two wild strains of the fungus had distinctly different chlorflavonin-producing capabilities. One strain produced 25 ?g of chlorflavonin per ml per 4 to 5 days in a pilot scale fermentor with stirring, using a medium containing corn steep liquor and glucose. Production of antibiotic was favored by high rates of agitation-aeration. Crude chlorflavonin was extracted from the whole brew with a hydrocarbon solvent and then purified by recrystallization from benzene and petroleum ether. The overall yield from fermentation brew to pure product was 50%.

Munden, J. E.; Butterworth, D.; Hanscomb, G.; Verrall, M. S.

1970-01-01

394

Sordarin, an antifungal agent with a unique mode of action  

PubMed Central

Summary The sordarin family of compounds, characterized by a unique tetracyclic diterpene core including a norbornene system, inhibits protein synthesis in fungi by stabilizing the ribosome/EF2 complex. This mode of action is in contrast to typical antifungals, which target the cell membrane. This unusual bioactivity makes sordarin a promising candidate for the development of new fungicidal agents, and provided the motivation for extensive research. Three total syntheses (by the Kato, Mander and Narasaka groups), modifications of the glycosyl unit, and changes to the diterpene core (Cuevas and Ciufolini models) will also be discussed in this review.

2008-01-01

395

3-Methoxysampangine, a novel antifungal copyrine alkaloid from Cleistopholis patens.  

PubMed Central

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.

Liu, S C; Oguntimein, B; Hufford, C D; Clark, A M

1990-01-01

396

Synthesis of biotin conjugates of the antifungal compound cymoxanil.  

PubMed

Biotin conjugates are of considerable value in investigating the mode of action of biologically active compounds. Two biotin conjugates related to the antifungal compound cymoxanil [1-(2-cyano-2-methoximinoacetyl)-3-ethyl urea] were prepared as the first step in an effort to employ display cloning to identify the compound's target site. In the first conjugate, prepared in five steps, the biotin moiety was attached at the position occupied by the ethyl group in cymoxanil. In the second conjugate, prepared in four steps, the biotin moiety was attached through the oxime functional group. PMID:11975188

Evans, Karen Anderson; Kane, Charles T; Tice, Colin M

2002-04-01

397

Antifungal Spectra of Actinomycetes Isolated from Tobacco1  

PubMed Central

Five species (28 strains) of actinomycetes isolated from tobacco were tested for antagonism against 12 species of storage and field fungi associated with tobacco. Two strains of Streptomyces albus were antagonistic against all test fungi. The actinomycetes grew more rapidly, produced more pigment, and had more pronounced antibiotic activity when grown at 36 C than at 28 C. Krasilnikov's synthetic medium, SMK-1, supported the greatest antifungal activity. More of the actinomycetes were antagonistic against more test fungi when grown for 20 days rather than 10 days. Images

Lukic, Anka; Welty, R. E.; Lucas, G. B.

1972-01-01

398

Cytotoxic and Antifungal Activities of Diverse ?-Naphthylamine Derivatives  

PubMed Central

Diverse ?-naphthylamine derivatives were easily prepared from corresponding aldimines derived from commercially available ?-naphthaldehyde and anilines or isomeric pyridinecarboxyaldehydes and ?-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 ?g/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 ?g/mL) some human opportunistic pathogenic fungi including yeasts, hialohyphomycetes, and dermatophytes.

Kouznetsov, Vladimir V.; Zacchino, Susana A.; Sortino, Maximiliano; Vargas Mendez, Leonor Y.; Gupta, Mahabir P.

2012-01-01

399

Antifungal and Antioxidant Activities of Pyrrolidone Thiosemicarbazone Complexes  

PubMed Central

Metal complexes of (Z)-2-(pyrrolidin-2-ylidene)hydrazinecarbothioamide (L) with Cu(II), Co(II), and Ni(II) chlorides were tested against selected types of fungi and were found to have significant antifungal activities. The free-radical-scavenging ability of the metal complexes was determined by their interaction with the stable free radical 2,2??-diphenyl-1-picrylhydrazyl, and all the compounds showed encouraging antioxidant activities. DFT calculations of the Cu complex were performed using molecular structures with optimized geometries. Molecular orbital calculations provide a detailed description of the orbitals, including spatial characteristics, nodal patterns, and the contributions of individual atoms.

Al-Amiery, Ahmed A.; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar

2012-01-01

400

Mechanism of action of efinaconazole, a novel triazole antifungal agent.  

PubMed

The mechanism of action of efinaconazole, a new triazole antifungal, was investigated with Trichophyton mentagrophytes and Candida albicans. Efinaconazole dose-dependently decreased ergosterol production and accumulated 4,4-dimethylsterols and 4?-methylsterols at concentrations below its MICs. Efinaconazole induced morphological and ultrastructural changes in T. mentagrophytes hyphae that became more prominent with increasing drug concentrations. In conclusion, the primary mechanism of action of efinaconazole is blockage of ergosterol biosynthesis, presumably through sterol 14?-demethylase inhibition, leading to secondary degenerative changes. PMID:23459486

Tatsumi, Yoshiyuki; Nagashima, Maria; Shibanushi, Toshiyuki; Iwata, Atsushi; Kangawa, Yumi; Inui, Fumie; Siu, William J Jo; Pillai, Radhakrishnan; Nishiyama, Yayoi

2013-05-01

401

A novel antifungal pyrrole derivative from Datura metel leaves.  

PubMed

Phytochemical investigation of the leaves of Datura metel Linn. led to the isolation of a new pyrrole derivative 1 which was characterised as 2beta-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1'-methylethyl pentanoate on the basis of spectral data analyses and chemical reactions. Compound 1 was endowed with antifungal activity and its MIC was found to be 87.5 microg/ml. Two proteins having molecular weights of 42 and 58 kD of Aspergillus fumigatus are potential targets for compound 1. PMID:15296098

Dabur, R; Ali, M; Singh, H; Gupta, J; Sharma, G L

2004-07-01

402

Antifungal activity of Lactobacillus against Microsporum canis, Microsporum gypseum and Epidermophyton floccosum  

PubMed Central

A total of 220 lactic acid bacteria isolates were screened for antifungal activity using Aspergillus fumigatus and Aspergillus niger as the target strains. Four Lactobacillus strains exhibited strong inhibitory activity on agar surfaces. All four were also identified as having strong inhibitory activity against the human pathogenic fungi Microsporum canis, Microsporum gypseum and Epidermophyton floccosum. One of the four lactobacilli, namely Lb. reuteri ee1p exhibited the most inhibition against dermatophytes. Cell-free culture supernatants of Lb. reuteri ee1p and of the non-antifungal Lb. reuteri M13 were freeze-dried and used to access and compare antifungal activity in agar plate assays and microtiter plate assays. Addition of the Lb. reuteri ee1p freeze-dried cell-free supernatant powder into the agar medium at concentrations greater than 2% inhibited all fungal colony growth. Addition of the powder at 5% to liquid cultures caused complete inhibition of fungal growth on the basis of turbidity. Freeze-dried supernatant of the non-antifungal Lb. reuteri M13 at the same concentrations had a much lesser effect. As Lb. reuteri M13 is very similar to the antifungal strain ee1p in terms of growth rate and final pH in liquid culture, and as it has little antifungal activity, it is clear that other antifungal compounds must be specifically produced (or produced at higher levels) by the anti-dermatophyte strain Lb. reuteri ee1p. Reuterin was undetectable in all four antifungal strains. The cell free supernatant of Lb. reuteri ee1p was analyzed by LC-FTMS using an Accela LC coupled to an LTQ Orbitrap XL mass spectrometer. The high mass accuracy spectrum produced by compounds in the Lb. reuteri ee1p strain was compared with both a multianalyte chromatogram and individual spectra of standard anti-fungal compounds, which are known to be produced by lactic acid bacteria. Ten antifungal metabolites were detected.

Guo, Jiahui; Brosnan, Brid; Furey, Ambrose; Arendt, Elke; Murphy, Padraigin; Coffey, Aidan

2012-01-01

403

Antifungal agents for secondary prophylaxis based on response to initial antifungal therapy in allogeneic hematopoietic stem cell transplant recipients with prior pulmonary aspergillosis.  

PubMed

We performed a prospective study to evaluate the efficacy and safety of secondary antifungal prophylaxis (SAP) for patients with a history of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, the prophylactic agents used were chosen based on treatment response to initial antifungal therapy. One hundred and thirty-six patients undergoing allo-HSCT with prior IPA were enrolled in this multicenter study. The agents of SAP included itraconazole in 24, voriconazole in 74, caspofungin in 32, and liposomal amphotericin B in 6. Eighty-eight patients had stable IPA and 48 had active IPA at the time of transplantation. The success rate of SAP was 91.2%. Twelve patients developed breakthrough invasive fungal disease (IFD), and none discontinued antifungal agents because drug-related adverse events. The incidence of breakthrough IFD was neither different among the different antifungal agents (P = .675) nor between patients with active and stable IPA (P = .080). The 1-year cumulative incidence of IFD and IPA relapse was 27.3% ± 4.5% and 24.7% ± 4.4%, respectively. Our data indicate that SAP with antifungal agents based on initial antifungal therapy has favorable efficacy and safety in allo-HSCT recipients with prior IPA. Active IPA might not increase the risk of breakthrough IFD after transplantation. PMID:24769013

Liu, Qifa; Lin, Ren; Sun, Jing; Xiao, Yang; Nie, Danian; Zhang, Yu; Huang, Fen; Fan, Zhiping; Zhou, Hongsheng; Jiang, Qianli; Zhang, Fuhua; Zhai, Xiao; Xu, Dan; Wei, Yongqiang; Song, Jiayin; Li, Yiqing; Feng, Ru

2014-08-01

404

Quantitative and qualitative analysis of the antifungal activity of allicin alone and in combination with antifungal drugs.  

PubMed

The antifungal activity of allicin and its synergistic effects with the antifungal agents flucytosine and amphotericin B (AmB) were investigated in Candida albicans (C. albicans). C. albicans was treated with different conditions of compounds alone and in combination (allicin, AmB, flucytosine, allicin + AmB, allicin + flucytosine, allicin + AmB + flucytosine). After a 24-hour treatment, cells were examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM) to measure morphological and biophysical properties associated with cell death. The clearing assay was conducted to confirm the effects of allicin. The viability of C. albicans treated by allicin alone or with one antifungal drug (AmB, flucytosine) in addition was more than 40% after a 24-hr treatment, but the viability of groups treated with combinations of more than two drugs was less than 32%. When the cells were treated with allicin alone or one type of drug, the morphology of the cells did not change noticeably, but when cells were treated with combinations of drugs, there were noticeable morphological changes. In particular, cells treated with allicin + AmB had significant membrane damage (burst or collapsed membranes). Classification of cells according to their cell death phase (CDP) allowed us to determine the relationship between cell viability and treatment conditions in detail. The adhesive force was decreased by the treatment in all groups compare to the control. Cells treated with AmB + allicin had a greater adhesive force than cells treated with AmB alone because of the secretion of molecules due to collapsed membranes. All cells treated with allicin or drugs were softer than the control cells. These results suggest that allicin can reduce MIC of AmB while keeping the same efficacy. PMID:22679493

Kim, Young-Sun; Kim, Kyung Sook; Han, Ihn; Kim, Mi-Hyun; Jung, Min Hyung; Park, Hun-Kuk

2012-01-01

405

Quantitative and Qualitative Analysis of the Antifungal Activity of Allicin Alone and in Combination with Antifungal Drugs  

PubMed Central

The antifungal activity of allicin and its synergistic effects with the antifungal agents flucytosine and amphotericin B (AmB) were investigated in Candida albicans (C. albicans). C. albicans was treated with different conditions of compounds alone and in combination (allicin, AmB, flucytosine, allicin + AmB, allicin + flucytosine, allicin + AmB + flucytosine). After a 24-hour treatment, cells were examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM) to measure morphological and biophysical properties associated with cell death. The clearing assay was conducted to confirm the effects of allicin. The viability of C. albicans treated by allicin alone or with one antifungal drug (AmB, flucytosine) in addition was more than 40% after a 24-hr treatment, but the viability of groups treated with combinations of more than two drugs was less than 32%. When the cells were treated with allicin alone or one type of drug, the morphology of the cells did not change noticeably, but when cells were treated with combinations of drugs, there were noticeable morphological changes. In particular, cells treated with allicin + AmB had significant membrane damage (burst or collapsed membranes). Classification of cells according to their cell death phase (CDP) allowed us to determine the relationship between cell viability and treatment conditions in detail. The adhesive force was decreased by the treatment in all groups compare to the control. Cells treated with AmB + allicin had a greater adhesive force than cells treated with AmB alone because of the secretion of molecules due to collapsed membranes. All cells treated with allicin or drugs were softer than the control cells. These results suggest that allicin can reduce MIC of AmB while keeping the same efficacy.

Han, Ihn; Kim, Mi-Hyun; Jung, Min Hyung; Park, Hun-Kuk

2012-01-01

406

Cordymin, an antifungal peptide from the medicinal fungus Cordyceps militaris.  

PubMed

Cordymin, an antifungal peptide with a molecular mass of 10,906 Da and an N-terminal amino acid sequence distinct from those of previously reported proteins, was purified from the medicinal mushroom Cordyceps militaris. The isolation protocol comprised ion exchange chromatography of the aqueous extract on SP-Sepharose and Mono S and gel filtration on Superdex 75 by a fast protein liquid chromatography system. Cordymin was adsorbed on both cation exchangers. The peptide inhibited mycelial growth in Bipolaris maydis, Mycosphaerella arachidicola, Rhizoctonia solani and Candida albicans with an IC(50) of 50 ?M, 10 ?M, 80 ?M, and 0.75 mM, respectively. However, there was no effect on Aspergillus fumigatus, Fusarium oxysporum and Valsa mali when tested up to 2 mM. The antifungal activity of the peptide was stable up to 100°C and in the pH range 6-13, and unaffected by 10 mM Zn(2+) and 10 mM Mg(2+). Cordymin inhibited HIV-1 reverse transcriptase with an IC(50) of 55 ?M. Cordymin displayed antiproliferative activity toward breast cancer cells (MCF-7) but there was no effect on colon cancer cells (HT-29). There was no mitogenic activity toward mouse spleen cells and no nitric oxide inducing activity toward mouse macrophages when tested up to 1 mM. PMID:20739167

Wong, Jack H; Ng, Tzi Bun; Wang, Hexiang; Sze, Stephen Cho Wing; Zhang, Kalin Yanbo; Li, Qi; Lu, Xiaoxu

2011-03-15

407

Design, characterization, and in vitro evaluation of antifungal polymeric films.  

PubMed

The objective of the present paper was the development and the full characterization of antifungal films. Econazole nitrate (ECN) was loaded in a polymeric matrix formed by chitosan (CH) and carbopol 971NF (CB). Polyethylene glycol 400 and sorbitol were used as plasticizing agents. The mechanical properties of films were poorer when the drug was loaded, probably because crystals of ENC produces network outages and therefore reduces the polymeric interactions between the polymers. Polymers-ECN and CH-CB interactions were analyzed by Fourier-transform infrared spectroscopy (FTIR), thermal gravimetry analysis, and differential thermal analysis (DTA-TGA). ECN did not show structure alterations when loaded into the films. In scanning electron microphotographs and atomic force microscopy analysis, films prepared with CB showed an evident wrinkle pattern probably due to the strong interactions between the polymers, which were observed by FTIR and DTA-TGA. The in vitro activity of the formulations against Candida krusei and Candida parapsilosis was twice as greater as the commercial cream, probably as a result of the antifungal combination of the drug with the CH activity. All these results suggest that these polymeric films containing ECN are potential candidates in view of alternatives dosages forms for the treatment of the yeast assayed. PMID:23225117

Real, Daniel A; Martinez, María V; Frattini, Agustín; Soazo, Marina; Luque, Alicia G; Biasoli, Marisa S; Salomon, Claudio J; Olivieri, Alejandro C; Leonardi, Darío

2013-03-01

408

Antifungal activity of some essential oils against toxigenic Aspergillus species.  

PubMed

Increasing attentions have been paid on the application of essential oils and plant extracts for control of postharvest pathogens due to their natural origin and less appearance of resistance in fungi pathogens. Some Aspergillus species are toxigenic and responsible for many cases of food and feed contamination. Some Toxins that produce with some Aspergillus species are known to be potent hepatocarcinogens in animals and humans. The present work evaluated the parameters of antifungal activity of the essential oils of Zataria multiflora, Thymus migricus, Satureja hortensis, Foeniculum vulgare, Carum capticum and thiabendazol fungicide on survival and growth of different species of Aspergillus. Aerial part and seeds of plant species were collected then dried and its essential oils isolated by means of hydrodistillation. Antifungal activity was evaluated in vitro by poisonous medium technique with PDA medium at six concentrations. Results showed that all essential oils could inhibit the growth of Aspergillus species. The essential oil with the best effect and lowest EC50 and MIC (Minimum Inhibitory Concentration) was Z. multiflora (223 microl/l and 650 microl/l, respectively). The chemical composition of the Z. multiflora essential oil was analyzed by GC-MS. PMID:21534488

Alizadeh, Alireza; Zamani, Elham; Sharaifi, Rohollah; Javan-Nikkhah, Mohammad; Nazari, Somayeh

2010-01-01

409

Lipidome analysis reveals antifungal polyphenol curcumin affects membrane lipid homeostasis  

PubMed Central

This study shows that antifungal curcumin (CUR), significantly depletes ergosterol levels in Candida albicans. CUR while displaying synergy with fluconazole (FLC) lowers ergosterol. However, CUR alone at its synergistic concentration (lower than MIC50), could not affect ergosterol contents. For deeper insight of CUR effects on lipids, we performed high throughput mass spectroscopy (MS) based lipid profiling of C. albicans cells. The lipidome analysis revealed that there were no major changes in PGLs composition following CUR treatment of Candida, however, significant differences in molecular species of PGLs were detected. Among major SPLs, CUR treatment resulted in the reduction of ceramide and accumulation of IPCs levels. The lipidome of CUR treated cells confirmed a dramatic drop in the ergosterol levels with a simultaneous accumulation of its biosynthetic precursors. This was further supported by the fact that the mutants defective in ergosterol biosynthesis (ERG2 and ERG11) and those lacking the transcription factor regulating ergosterol biosynthesis, UPC2, were highly susceptible to CUR. Our study first time shows that CUR, for its antifungal activity, targets and down regulates ?5, 6 desaturase (ERG3) resulting in depletion of ergosterol. This results in parallel accumulation of ergosterol biosynthetic precursors, generation of ROS and cell death.

Sharma, Monika; Dhamgaye, Sanjiveeni; Singh, Ashutosh; Prasad, Rajendra

2013-01-01

410

Structural Basis of Human CYP51 Inhibition by Antifungal Azoles  

SciTech Connect

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.

Strushkevich, Natallia; Usanov, Sergey A.; Park, Hee-Won (Toronto); (IBC-Belarus)

2010-09-22

411

Glycerol enhances the antifungal activity of dairy propionibacteria.  

PubMed

Dairy propionibacteria are widely used in starter cultures for Swiss type cheese. These bacteria can ferment glucose, lactic acid, and glycerol into propionic acid, acetic acid, and carbon dioxide. This research examined the antifungal effect of dairy propionibacteria when glycerol was used as carbon source for bacterial growth. Five type strains of propionibacteria were tested against the yeast Rhodotorula mucilaginosa and the molds Penicillium commune and Penicillium roqueforti. The conversion of (13)C glycerol by Propionibacterium jensenii was followed with nuclear magnetic resonance. In a dual culture assay, the degree of inhibition of the molds was strongly enhanced by an increase in glycerol concentrations, while the yeast was less affected. In broth cultures, decreased pH in glycerol medium was probably responsible for the complete inhibition of the indicator fungi. NMR spectra of the glycerol conversion confirmed that propionic acid was the dominant metabolite. Based on the results obtained, the increased antifungal effect seen by glycerol addition to cultures of propionibacteria is due to the production of propionic acid and pH reduction of the medium. PMID:21331381

Lind, Helena; Broberg, Anders; Jacobsson, Karin; Jonsson, Hans; Schnürer, Johan

2010-01-01

412

Antifungal saponins from bulbs of white onion, Allium cepa L.  

PubMed

Three saponins, named ceposide A, ceposide B, and ceposide C were isolated from the bulbs of white onion, Allium cepa L. Elucidation of their structure was carried out by comprehensive spectroscopic analyses, including 2D NMR spectroscopy and mass spectrometry, and chemical evidences. The structures of the compounds were identified as (25R)-furost-5(6)-en-1?,3?,22?,26-tetraol 1-O-?-D-xylopyranosyl 26-O-?-D-rhamnoyranosyl-(1?2)-O-?-D-galactopyranoside (ceposide A), (25R)-furost-5(6)-en-1?,3?,22?,26-tetraol 1-O-?-D-xylopyranosyl 26-O-?-D-rhamnoyranosyl-(1?2)-O-?-D-glucopyranoside (ceposide B), and (25R)-furost-5(6)-en-1?,3?,22?,26-tetraol 1-O-?-D-galactopyranosyl 26-O-?-D-rhamnoyranosyl-(1?2)-O-?-D-galactopyranoside (ceposide C). The isolated compounds, alone and in combinations, were evaluated for their antimicrobial activity on ten fungal species. Antifungal activity of all three saponins increased with their concentration and varied with the following rank: ceposide B>ceposide A-ceposide C. We found a significant synergism in the antifungal activity of the three ceposides against Botrytis cinerea and Trichoderma atroviride, because growth of these fungi was strongly inhibited when the three saponins were applied in combination. In contrast, Fusarium oxysporum f. sp. lycopersici, Sclerotium cepivorum and Rhizoctonia solani were very little affected by saponins. PMID:22169018

Lanzotti, Virginia; Romano, Adriana; Lanzuise, Stefania; Bonanomi, Giuliano; Scala, Felice

2012-02-01

413

Methylxanthine inhibit fungal chitinases and exhibit antifungal activity.  

PubMed

Chitinases are necessary for fungal cell wall remodeling and cell replication. Methylxanthines have been shown to competitively inhibit family 18 chitinases in vitro. We sought to determine the effects of methylxanthines on fungal chitinases. Fungi demonstrated variable chitinase activity and incubation with methylxanthines (0.5-10 mM) resulted in a dose-dependent decrease in this activity. All fungi tested, except for Candida spp., demonstrated growth inhibition in the presence of methylxanthines at a concentration of 10 mM. India ink staining demonstrated impaired budding and decreased cell size for methylxanthine-treated Cryptococcus neoformans. C. neoformans and Aspergillus fumigatus treated with pentoxifylline also exhibited abnormal cell morphology. In addition, pentoxifylline-treated C. neoformans exhibited increased susceptibility to calcofluor and a leaky melanin phenotype consistent with defective cell wall function. Our data suggest that a variety of fungi express chitinases and that methylxanthines have antifungal properties related to their inhibition of fungal chitinases. Our results highlight the potential utility of targeting chitinases in the development of novel antifungal therapies. PMID:21968902

Tsirilakis, Kalliope; Kim, Christy; Vicencio, Alfin G; Andrade, Christopher; Casadevall, Arturo; Goldman, David L

2012-03-01

414

Antifungal activity of lectins against yeast of vaginal secretion  

PubMed Central

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 256?g/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.

Gomes, Bruno Severo; Siqueira, Ana Beatriz Sotero; de Cassia 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 Lucia Figueiredo

2012-01-01

415

Recent patents on antibacterial, antifungal and antiviral properties of tea.  

PubMed

Teas have beneficial effects on human health including cardioprotective, anticarcinogenic, antibacterial, antiviral and antifungal activity. The precise antimicrobial spectrum of tea is difficult to be defined due to variation in the methods of testing that have been used. Antibacterial effects of tea have been demonstrated against a number of microorganisms including Staphylococcus aureus, Vibrio cholerae, Escherichia coli, Shigella spp., Salmonella spp., Bacillus spp., Klebsiella spp. and Pseudomonas aeruginosa. Teas and tea ingredients seem to have both bactericidal and bacteriostatic actions. In addition, tea catechins have been shown to modify the antibiotic sensitivity of bacteria and to alter the expression of factors that determine bacterial virulence. Antiviral effects of green tea have been demonstrated against the influenza virus, as well as against the Herpes simplex virus, tobacco mosaic virus, enterovirus, rotavirus, Epstein Barr virus, HIV virus. Yet, green tea catechins have been shown to have antiviral activities against HIV infection. Antifungal effects of tea have been reported against Candida albicans, Trichophyton mentagrophytes, and Trichophyton rubrum. The present paper describes recent patents on antimicrobial effect of teas and tea ingredients. PMID:22353001

Yiannakopoulou, Eugenia Ch

2012-04-01

416

Empirical antifungal therapy in selected patients with persistent febrile neutropenia.  

PubMed

Universal empirical antifungal therapy (EAT) in patients with unexplained persistent febrile neutropenia (PFN) is the standard of care, but EAT could be applied in selected patients on the basis of clinical criteria and risk factors. A prospective interventional study was carried out to analyse the incidence and related mortality of invasive fungal infection (IFI) in patients with PFN according to whether or not EAT was indicated. EAT was indicated according to the following criteria: (a) severe sepsis or septic shock; (b) focused infection: lung, central nervous system, sinus, abdominal or skin; (c) individualized clinical decision in patients at high risk. Sixty-six (19%) of 347 episodes of febrile neutropenia fulfilled PFN criteria, 97% with a haematological malignancy. Just 26 (39.4%) were treated with EAT. The overall IFI incidence was 4.5%. In the group that received EAT, three patients developed IFI (11.5%), in comparison with none in the group that did not receive it (P=0.04, RR 2.7:1.9-3.8). IFI-related mortality was null in the group that did not receive EAT and 8% (two of 26 patients) in the group that received EAT. These data suggest that in patients with PFN, EAT in selected patients may be safe and avoid unnecessary antifungal therapy. PMID:19525983

Aguilar-Guisado, M; Espigado, I; Cordero, E; Noguer, M; Parody, R; Pachón, J; Cisneros, J M

2010-01-01

417

Treatment of dermatophytosis by a new antifungal agent 'apigenin'.  

PubMed

Dermatophytes are the most common causative agents of cutaneous mycosis and remain a major public health problem in spite of the availability of an increasing number of antifungal drugs. It was, therefore considered necessary to pursue the screening of different extracts (compounds) of selected traditional medicinal plants reportedly having antidermatophyte potential. The aim of this study was to isolate and identify specific compound from the most active extract (free flavonoid) of stem of Terminalia chebula of the selected plants to treat dermatophytosis induced on experimental mice. Mice which were experimentally induced with Trichophyton mentagrophytes were grouped in six of five animals each. To treat the lesions on infected mice, two concentrations of isolated apigenin ointment, i.e. 2.5 mg g(-1) (Api I) and 5 mg g(-1) (Api II), and terbinafine (standard) of concentration 5 mg g(-1) were used. Complete recovery from the infection was recorded on 12th day of treatment for reference drug Terbinafine and Api II (5 mg g(-1) ) concentration of ointment, whereas Api I (2.5 mg g(-1) ) ointment showed complete cure on 16th day of treatment. Fungal burden was also calculated by culturing skin scraping from infected mice's of different groups. Apigenin has shown potency as the infected animals recover completely by Api II comparable to the standard drug in 12th day. So Apigenin can be explored as an antifungal agent in the clinical treatment of dermatophytosis in future. PMID:24708558

Singh, Geeta; Kumar, Padma; Joshi, Suresh Chandra

2014-08-01

418

Antifungal properties of Canavalia ensiformis urease and derived peptides.  

PubMed

Ureases (EC 3.5.1.5) are metalloenzymes that hydrolyze urea into ammonia and CO(2). These proteins have insecticidal and fungicidal effects not related to their enzymatic activity. The insecticidal activity of urease is mostly dependent on the release of internal peptides after hydrolysis by insect digestive cathepsins. Jaburetox is a recombinant version of one of these peptides, expressed in Escherichia coli. The antifungal activity of ureases in filamentous fungi occurs at submicromolar doses, with damage to the cell membranes. Here we evaluated the toxic effect of Canavalia ensiformis urease (JBU) on different yeast species and carried out studies aiming to identify antifungal domain(s) of JBU. Data showed that toxicity of JBU varied according to the genus and species of yeasts, causing inhibition of proliferation, induction of morphological alterations with formation of pseudohyphae, changes in the transport of H(+) and carbohydrate metabolism, and permeabilization of membranes, which eventually lead to cell death. Hydrolysis of JBU with papain resulted in fungitoxic peptides (~10 kDa), which analyzed by mass spectrometry, revealed the presence of a fragment containing the N-terminal sequence of the entomotoxic peptide Jaburetox. Tests with Jaburetox on yeasts and filamentous fungi indicated a fungitoxic activity similar to ureases. Plant ureases, such as JBU, and its derived peptides, may represent a new alternative to control medically important mycoses as well as phytopathogenic fungi, especially considering their potent activity in the range of 10(-6)-10(-7)M. PMID:22922160

Postal, Melissa; Martinelli, Anne H S; Becker-Ritt, Arlete B; Ligabue-Braun, Rodrigo; Demartini, Diogo R; Ribeiro, Suzanna F F; Pasquali, Giancarlo; Gomes, Valdirene M; Carlini, Celia R

2012-11-01

419

Antifungal Properties of Haem Peroxidase from Acorus calamus  

PubMed Central

• 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.

GHOSH, MODHUMITA

2006-01-01

420

Evaluation of the antifungal potential of Brazilian Cerrado medicinal plants.  

PubMed

Therapeutic limitations, development of fungal drug resistance, drug-related toxicity, drug interactions and insufficient bioavailability of the currently available antifungal drugs have made the development of drugs necessary that would be able to treat the emerging fungal infections. The Cerrado is the second greater biome of Brazil and it was identified as one of the most distinguished biomes of South America, becoming an important source of innovative vegetal molecules to treat several conditions. Thus, the objective of this study was to evaluate the antifungal potential of Cerrado plants, mainly those used to treat infections and wounds. A total of 57 extracts were screened by the agar-well diffusion technique against Candida albicans and Trichophyton rubrum. The most promising extracts were tested in smaller concentrations and their minimal inhibitory concentrations (MIC) were determined by microdilution method. Results were analysed statistically by anova tests. Extracts of Kielmeyera coriacea, Renealmia alpinia, Stryphnodendron adstringens and Tabebuia caraiba were very active against T. rubrum, presented geometric means of the MIC values between 170.39 and 23.23 microg ml(-1). Extracts of Cerrado plants are of particular interest as source of new agents for the treatment of dermatophytic infections. PMID:19207849

Melo e Silva, Fernanda; de Paula, José Elias; Espindola, Laila Salmen

2009-11-01

421

Characterization of the Escherichia coli Antifungal Protein PPEBL21  

PubMed Central

An antifungal protein isolated from Escherichia coli BL21 (PPEBL21) and predicted to be alcohol dehydrogenase (ADH) was subjected to biological characterization. The PPEBL21, indeed, demonstrated propionaldehyde-specific ADH activity. The Km and Vmax of PPEBL21 were found to be 644.8 ?M and 1.2?U/mg, respectively. In-gel activity assay also showed that PPEBL21 was a propionaldehyde-specific ADH. The pI of PPEBL21 was observed to be 7.8. PPEBL21 was found to be stable up to a temperature of 40°C with optimum activity at pH 7.5. The decrease in pH decreased the activity of PPEBL21. These results suggested that PPEBL21 having alcohol dehydrogenase activity and stability at significantly high temperature might be an important lead antifungal molecule. Experiments were performed to identify the possible target of PPEBL21 in the pathogen A. fumigatus. Results revealed that PPEBL21 inhibited completely the expression of a 16?kDa protein in A. fumigatus. The?16 kDa protein of A. fumigatus targeted by PPEBL21 was identified as a hypothetical protein by peptide mass fingerprinting. It is thus hypothesized that a 16?kDa factor is essentially required by A. fumigatus for survival and its impaired synthesis due to treatment with PPEBL21 may lead to the death of pathogen.

Yadav, V.; Mandhan, R.; Kumar, M.; Gupta, J.; Sharma, G. L.

2010-01-01

422

Chemical composition, antifungal and insecticidal activities of Hedychium essential oils.  

PubMed

The antimicrobial properties of essential oils have been documented, and their use as "biocides" is gaining popularity. The aims of this study were to analyze the chemical composition and assess the biological activities of Hedychium essential oils. Oils from 19 Hedychium species and cultivars were analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. The antifungal and insecticidal activities of these oils were tested against Colletotrichum acutatum, C. fragariae, and C. gloeosporioides, and three insects, the azalea lace bug (Stephanitis pyrioides), the yellow fever mosquito (Aedes aegypti), and the red imported fire ant (Solenopsis invicta). Hedychium oils were rich in monoterpenes and sesquiterpenes, especially 1,8-cineole (0.1%-42%), linalool (<0.1%-56%), a-pinene (3%-17%), b-pinene (4%-31%), and (E)-nerolidol (0.1%-20%). Hedychium oils had no antifungal effect on C. gloeosporioides, C. fragariae, and C. acutatum, but most Hedychium oils effectively killed azalea lace bugs. The oils also show promise as an adult mosquito repellent, but they would make rather poor larvicides or adulticides for mosquito control. Hedychium oils acted either as a fire ant repellent or attractant, depending on plant genotype and oil concentration. PMID:23579997

Sakhanokho, Hamidou F; Sampson, Blair J; Tabanca, Nurhayat; Wedge, David E; Demirci, Betul; Baser, Kemal Husnu Can; Bernier, Ulrich R; Tsikolia, Maia; Agramonte, Natasha M; Becnel, James J; Chen, Jian; Rajasekaran, Kanniah; Spiers, James M

2013-01-01

423

Antifungals: Need to Search for a New Molecular Target  

PubMed Central

In the 1990s, drug resistance has become an important problem in a variety of infectious diseases including human immunodeficiency virus infection, tuberculosis, and other bacterial infections which have profound effects on human health. At the same time, there have been dramatic increase in the incidence of fungal infections, which are probably the result of alterations in immune status associated with the acquired immuno deficiency syndrome epidemic, cancer chemotherapy, and organ and bone marrow transplantation. The rise in the incidence of fungal infections has exacerbated the need for the next generation of antifungal agents, since many of the currently available drugs have undesirable side effects, are ineffective against new or reemerging fungi, or lead to the rapid development of the resistance. This review will focus on the pathogenic yeast Candida albicans, since a large body of work on the factors and mechanism associated with antifungal drug resistance in this organism is reported sufficiently. It will certainly elaborate the probable molecular targets for drug design, discovered to date.

Sangamwar, A. T.; Deshpande, U. D.; Pekamwar, S. S.

2008-01-01

424

The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals against Candida parapsilosis species complex.  

PubMed

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

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

425

Antifungal therapy in the treatment of chronic rhinosinusitis: A meta-analysis  

PubMed Central

Background: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Because fungi were postulated as a potential cause of CRS in the late 1990s, contrasting articles have advocated and refuted the use of antifungal agents in its management. Although good research shows an interaction of the immune system with fungus in CRS, e.g., allergic fungal sinusitis (AFS), this does not imply that fungi are the cause of CRS or that antifungals will be effective in management. This study was designed to assess the potential advantage of either topical or systemic antifungal therapy in the symptomatic treatment of CRS to aid physicians in making informed decisions about treating patients with CRS. Methods: A systematic review of the literature was performed with meta-analysis. All studies obtained from searches were reviewed and trials meeting the eligibility criteria were selected. CRS was defined using either the European Position Paper on Rhinosinusitis and Nasal Polyps or American Academy of Otolaryngology–Head and Neck Surgery criteria. Authors were contacted and original data were used for data analysis. Results: Five studies investigating topical antifungals and one investigating systemic antifungals met the inclusion criteria. All trials were double blinded and randomized. Pooled meta-analysis showed no statistically significant benefit of topical or systemic antifungals over placebo. Symptoms scores statistically favored the placebo group for this outcome. Adverse event reporting was higher in the antifungal group. Conclusion: Reported side-effects of antifungal therapies may outweigh any potential benefits of treatment based on this meta-analysis and the authors therefore do not advocate the use antifungal treatment in the management of CRS.

Harvey, Richard J.; Rimmer, Janet; Gallagher, Richard M.; Sacks, Raymond

2012-01-01

426

Antifungal Susceptibility Testing Method for Dermatophytes -Determination of MIC and MFC Values-.  

PubMed

In vitro antifungal susceptibility of pathogenic fungi is important information for physicians when selecting an appropriate antifungal drug, deciding the route of drug administration, surveying resistant strains, and so on. Although both the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) are well known endpoints of antifungal susceptibility, the MIC is by far the more highly referred in clinical laboratories. In fact, while methods for determining the MIC have been standardized in Japan and the West to ensure accuracy and reproducibility of the results, by contrast, scant attention has been paid to standardizing methods for determining the MFC. The same preference for MIC topical antifungal drugs for dermatophytes are concerned. In 1999, the Japanese Society of Medical Mycology published a new, standardized method of testing the MIC for dermatophytes and this has since been widely adopted. Nonetheless, the fact remains that the MFC is still determined using methods derived from antifungal pharmacology. Recently in Japan, however, the MFC of topical antifungal drugs has begun attracting more attention due to the development of new antifungal agents with fungicidal activity. These new developments call for improving our understanding of both the MIC and MFC as endpoints of antifungal susceptibility, and for standardizing methods for determining the MFC.The present paper has two objectives : first, to overview the MIC and MFC for topical drugs as endpoints of antifungal susceptibility; and second, to describe a novel test based on the standardized broth microdilution method combined with the trans-well system and neutral red, which we recently developed in our laboratory for directly measuring the MFC. PMID:24943208

Koga, Hiroyasu

2014-01-01

427

In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections  

PubMed Central

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.

Yuen, Kwok Yong; Wang, Yu; Yang, Dan; Samaranayake, Lakshman Perera

2014-01-01

428

In vitro and in vivo activity of a novel antifungal small molecule against Candida infections.  

PubMed

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

Wong, Sarah Sze Wah; Kao, Richard Yi Tsun; Yuen, Kwok Yong; Wang, Yu; Yang, Dan; Samaranayake, Lakshman Perera; Seneviratne, Chaminda Jayampath

2014-01-01

429

Correlation between Antifungal Susceptibilities of Coccidioides immitis In Vitro and Antifungal Treatment with Caspofungin in a Mouse Model  

PubMed Central

Caspofungin (Merck Pharmaceuticals) was tested in vitro against 25 clinical isolates of Coccidoides immitis. In vitro susceptibility testing was performed in accordance with the National Committee for Clinical Laboratory Standards document M38-P guidelines. Two C. immitis isolates for which the caspofungin MICs were different were selected for determination of the minimum effective concentration (MEC), and these same strains were used for animal studies. Survival and tissue burdens of the spleens, livers, and lungs were used as antifungal response markers. Mice infected with strain 98-449 (48-h MIC, 8 ?g/ml; 48-h MEC, 0.125 ?g/ml) showed 100% survival to day 50 when treated with caspofungin at ?1 mg/kg. Mice infected with strain 98-571 (48-h MIC, 64 ?g/ml; 48-h MEC, 0.125 ?g/ml) displayed ?80% survival when the treatment was caspofungin at ?5 mg/kg. Treatment with caspofungin at 0.5, 1, 5, or 10 mg/kg was effective in reducing the tissue fungal burdens of mice infected with either isolate. When tissue fungal burden study results were compared between strains, caspofungin showed no statistically significant difference in efficacy in the organs of the mice treated with both strains. A better in vitro-in vivo correlation was noted when we used the MEC instead of the MIC as the endpoint for antifungal susceptibility testing. Caspofungin may have a role in the treatment of coccidioidomycosis.

Gonzalez, Gloria M.; Tijerina, Rolando; Najvar, Laura K.; Bocanegra, Rosie; Luther, Michael; Rinaldi, Michael G.; Graybill, John R.

2001-01-01

430

Bioassay-guided isolation and identification of antifungal compounds from ginger.  

PubMed

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

Ficker, C; Smith, M L; Akpagana, K; Gbeassor, M; Zhang, J; Durst, T; Assabgui, R; Arnason, J T

2003-09-01

431

Clauraila E from the roots of Clausena harmandiana and antifungal activity against Pythium insidiosum.  

PubMed

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

Sriphana, Uraiwan; Thongsri, Yordhathai; Prariyachatigul, Chularut; Pakawatchai, Chaveng; Yenjai, Chavi

2013-09-01

432

Enhancement of the Antifungal Activity of Antimicrobial Drugs by Eugenia uniflora L.  

PubMed Central

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.

Santos, Karla K.A.; Matias, Edinardo F.F.; Tintino, Saulo R.; Souza, Celestina E.S.; Braga, Maria F.B.M.; Guedes, Glaucia M.M.; Costa, Jose G.M.; Menezes, Irwin R.A.

2013-01-01

433

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

PubMed

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. PMID:17018648

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

434

Recent advances in the use of cyclodextrins in antifungal formulations.  

PubMed

Cyclodextrins are usually used in antifungal formulations as auxiliary substances to improve solubility, stability, or other physicochemical properties of the active compound. Nevertheless, more and more research and practical use results indicate that cyclodextrins might also act as active compounds in pharmaceutical formulations. The biological effects of cyclodextrins, important for their use within antimycotic formulations, can be divided into: effects based on the ability of cyclodextrins to form inclusion complexes with endogenous substances (membrane lipids, cellular cholesterol), effects based on formation of inclusion complexes with component parts of fungi cells, and effects based on the chemical nature of cyclodextrins and their derivatives. This review will cover the advances in research of biological activity of cyclodextrins with focus on their properties responsible for their synergistic effect with antimycotic compounds. PMID:24083792

Macaev, Fliur; Boldescu, Veaceslav; Geronikaki, Athina; Sucman, Natalia

2013-01-01

435

Antifungal Activity of Eugenol against Penicillium, Aspergillus, and Fusarium Species.  

PubMed

The antifungal activity of eugenol in a model system against aspergilli (Aspergillus niger, Aspergillus terreus, and Emericella nidulans), penicilli (Penicillium expansum, Penicillium glabrum, and Penicillium italicum), and fusaria (Fusarium oxysporum and Fusarium avenaceum) was investigated. Minimum detection time (time to attain a colony diameter of 1 cm) and the kinetic parameters were evaluated. The effectiveness of the active compound seemed to be strain or genus dependent; 100 mg/liter represented a critical value for P. expansum, P. glabrum, P. italicum, A. niger, and E. nidulans because a further increase of eugenol resulted in fungistatic activity. The radial growth of A. terreus and F. avenaceum was inhibited at 140 mg/liter, and growth of F. oxysporum was completely inhibited at 150 mg/liter. PMID:20537272

Campaniello, Daniela; Corbo, Maria Rosaria; Sinigaglia, Milena

2010-06-01

436

Partial identification of antifungal compounds from Punica granatum peel extracts.  

PubMed

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

Glazer, Ira; Masaphy, Segula; Marciano, Prosper; Bar-Ilan, Igal; Holland, Doron; Kerem, Zohar; Amir, Rachel

2012-05-16

437

The antifungal constituents from the seeds of Itoa orientalis.  

PubMed

Three new phenolic constituents, itolide A (1), itolide B (2), itoside P (3), and 1D-3-deoxy-3-hydroxymethyl-myo-inositol (4), which is described herein for the first time as a natural product, were isolated along with four other known compounds (5 to 8) from the methanol extract of the seeds of Itoa orientalis Hemsl by the activity-guided fractionation. Their structures were determined by spectroscopic means. Compounds 1 to 8 exhibited antifungal activities against Sclerotium rolfsii with IC?? values ranging from 60.12 to 240.00 ?M and against Rhizoctonia solani with IC?? values ranging from 45.34 to 233.14 ?M, respectively, and compounds 1, 2, 5 exhibited cytotoxic activity against Tn5B1-4 insect cell line with EC?? values of 203.68, 93.41 and 40.37 ?M, respectively. PMID:22233862

Tang, WenWei; Xu, HanHong; Zeng, DongQiang; Yu, LiJia

2012-04-01

438

Antifungal constituents of Clytostoma ramentaceum and Mansoa hirsuta.  

PubMed

Ethanol extracts of Clytostoma ramentaceum Bur. & K. Schum and Mansoa hirsuta DC. (Bignoniaceae) inhibited the growth of standardized cultures of Aspergillus niger and Fusarium oxysporum, at concentrations of 400 microg and 500 microg, in bioautographic assays. The activity-guided fractionation of C. ramentaceum extract afforded ursolic acid and 2-(3',4'-dihydroxyphenyl) ethanol, both active against the test fungi (100 microg). These compounds are reported for the first time in C. ramentaceum and were not detected in M. hirsuta extract, according to HPLC analysis. The bioguided study of M. hirsuta resulted in five active fractions (100 to 200 microg), whose GC-MS analysis allowed us to identify 11 compounds, mostly alkanols and alkanodiols, that may be regarded as the antifungal constituents of M. hirsuta. PMID:15287070

Rocha, Alessandra Duarte; de Oliveira, Alaíde Braga; de Souza Filho, José Dias; Lombardi, Júlio Antônio; Braga, Fernão Castro

2004-06-01

439

CAY-1, a novel antifungal compound from cayenne pepper.  

PubMed

CAY-1, a novel saponin from Capsicum frutescens (commercially known as cayenne pepper) was investigated to determine its in vitro antifungal activity, mechanism of action and mammalian cell cytotoxicity. CAY-1 was active against 16 different fungal strains, including Candida spp. and Aspergillus fumigatus [minimum inhibitory concentrations (MIC) ranging from 4 to 16 microg ml(-1)], and was especially active against Cryptococcus neoformans (90% inhibition at 1 microg ml(-1)). Synergistic activity was also observed between CAY-1 and amphotericin B against Candida albicans and A. fumigatus. No significant cytotoxicity was demonstrated when CAY-1 was tested against 55 mammalian cell lines at up to 100 microg ml(-1). Importantly, CAY-1 appears to act by disrupting the membrane integrity of fungal cells. PMID:12627807

Renault, S; De Lucca, A J; Boue, S; Bland, J M; Vigo, C B; Selitrennikoff, C P

2003-02-01

440

Strength in numbers: antifungal strategies against fungal biofilms.  

PubMed

Pathogenic fungi have the capacity to form tenacious biofilm structures that are notoriously unresponsive to antifungal therapies. Fungal biofilms are ubiquitous, located all over the human host, including the oral cavity, respiratory tract, gastrointestinal tract, urinary tract, wounds and upon biomedical devices. This latter category represents one of the greatest hurdles in clinical management, where the presence of inert substrates such as a catheter provides a reservoir for fungal biofilm development. Here, Candida albicans is the most adept at forming biofilms and is the principal nosocomial fungal pathogen based on its high rates of mortality, which are often associated with the biofilm lifestyle. This review will summarise some of the key fungal biofilm-forming organisms and their clinical significance and will discuss current and novel strategies to manage these hard-to-treat infections based on in vitro and in vivo studies. PMID:24359842

Ramage, Gordon; Robertson, Shaun N; Williams, Craig

2014-02-01

441

A sugarcane cystatin: recombinant expression, purification, and antifungal activity.  

PubMed

Plants possess several defense mechanisms against pathogenic attack. One of these defenses is the use of protease inhibitor proteins, which interfere in the development and growth of pathogens. Sugarcane productivity can be impacted by the plant's susceptibility to fungal diseases that result in production losses. A relevant line of investigation, therefore, is into the plant's natural defense mechanisms for the control of phytopathogens using cystatins-proteins that specifically inhibit cysteine proteases. In this paper, we discuss the expression, in Escherichia coli, of a sugarcane cystatin, its purification, antifungal activity, and circular dichroism to monitor correct folding. These studies revealed a secondary structure similar to that of the oryzacystatin I of rice. Moreover, the purified protein proved capable of inhibiting the growth of the filamentous fungus Trichoderma reesei, suggesting that it can also be employed to inhibit the growth of pathogenic sugarcane fungi. PMID:12207900

Soares-Costa, A; Beltramini, L M; Thiemann, O H; Henrique-Silva, F

2002-09-01

442

Clinical evaluation of clotrimazole. A broad-spectrum antifungal agent.  

PubMed

The efficacy and safety of the broad-spectrum, topically applied antifungal agent clotrimazole were evaluated in two double-blind, multicentric trials. Ten investigators reported on a total of 1,361 cases in which a 1% solution or a 1% cream formulation was compared with its respective vehicle. Clotrimazole was therapeutically effective, as confirmed by mycological cure (negative microscopy and culture) and clinical improvement, in tinea pedis, tinea cruris, tinea corporis, pityriasis versicolor, and cutaneous candidasis. Furthermore, species identification established the efficacy of clotrimazole against Trichophyton rubrum, T mentagrophytes, Epidermophyton floccosum, Microsporum canis, Malassezia furfur (Pityrosporum orbiculare), and Candida albicans. Safety was demonstrated by the low incidence of possibly drug-related adverse experiences, namely, 19 (2.7%) of 699 patients who were treated with clotrimazole, of whom four (0.6%) discontinued treatment. PMID:769697

Spiekermann, P H; Young, M D

1976-03-01

443

Synthesis and antifungal activity of two novel spermidine analogues.  

PubMed

Two spermidine analogues were synthesised and examined for antifungal activity. Both compounds used as 1 mM post-inoculation sprays reduced infection of barley seedlings by the powdery mildew fungus, Erysiphe graminis f.sp. hordei, infection of broad bean seedlings by the rust fungus, Uromyces viciae-fabae, and infection of apple seedlings by the powdery mildew fungus, Podosphaera leucotricha. Since these fungal pathogens cannot be cultured axenically, the effects of the two spermidine analogues on mycelial growth in vitro, as well as preliminary investigations on polyamine biosynthesis, were undertaken using the oat stripe pathogen, Pyrenophora avenae. Although neither compound affected radial growth of the fungus on plates, both analogues reduced fungal biomass in liquid culture substantially. The two spermidine analogues, used at a concentration of 1 mM, had no significant effect on the conversion of labelled ornithine into polyamines in P. avenae. PMID:9066105

Mackintosh, C A; Slater, L A; McClintock, C A; Walters, D R; Havis, N D; Robins, D J

1997-03-01

444

Antifungal activity of Curcuma longa grown in Thailand.  

PubMed

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

Wuthi-udomlert, M; Grisanapan, W; Luanratana, O; Caichompoo, W

2000-01-01

445

Pharmacodynamics and pharmacokinetics of antifungals for treatment of invasive aspergillosis.  

PubMed

Amphotericin B has been the only therapeutic option for invasive aspergillosis over decades. It acts by binding to membrane ergosterol, lipid peroxidation and proton-ATPase inhibition. Amphotericin B is eliminated unchanged via urine and feces. It displays a considerable toxicity, particularly infusion-related adverse events and renal damage. Continuous infusion and administration of lipidformulations of amphotericin B are strategies to improve its tolerability. Amphotericin B has a post-antifungal effect (PAFE), and its peak concentration is probably crucial for its fungicidal efficacy. The amphotericin B lipid-formulations display largely different pharmacokinetics. Kinetics of amphotericin B which is liberated from its lipid encapsulation in the plasma is similar for all three available lipid formulations. Azoles inhibit the synthesis of fungal cell membrane ergosterol. The triazoles itraconazole, voriconazole and posaconazole are active against Aspergilli. Voriconazole is the drug of choice for therapy of invasive aspergillosis. It is metabolized in the liver and metabolites are excreted via the kidneys. Posaconazole is licensed for antifungal prophylaxis in hematological high-risk patients and for salvage therapy of invasive aspergillosis. A variety of drug-drug interactions have to be considered with all azoles. The ratio between the area under the time-concentration profile (AUC) and the minimal inhibitory concentration (MIC) is the relevant pharmacokinetic/ pharmacodynamic parameter for azoles. Caspofungin the only echinocandin licensed for second line therapy of invasive aspergillosis is fungistatic to Aspergilli displaying a paradoxical pharmacodynamic effect. Caspofungin elimination is independent from renal function. Although it is metabolized in the liver its potential for drug interactions is moderate. PMID:23278532

Bellmann, Romuald

2013-01-01

446

In vitro antifungal activity of naftifine hydrochloride against dermatophytes.  

PubMed

The incidence of superficial dermatophytoses is high in developed countries, and there remains a need for effective topical antifungals. In this study, we evaluated the in vitro antifungal activity of naftifine hydrochloride, the active ingredient in naftifine hydrochloride cream and gel 1% and 2%, against dermatophytes. The MICs and minimum fungicidal concentrations (MFCs) of naftifine hydrochloride against 350 clinical strains, including Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Epidermophyton floccosum, and Microsporum canis, were determined using the CLSI methodology. Subsets from this test panel were subsequently tested in a time-kill assay at 0.125×, 0.25×, 0.5×, and 1× the MFC for each isolate. CFU counts were performed over a period of 48 h of incubation. Additionally, in order to determine the potential for resistance development, six strains were subjected to 15 serial passages in concentrations higher than the MIC for each strain. MICs were determined following each passage. The MIC range against the dermatophyte isolates tested was 0.015 to 1.0 ?g/ml, with naftifine hydrochloride being fungicidal against 85% of the Trichophyton species. The time-kill assay showed dose-dependent activity, with the greatest reduction in the numbers of CFU corresponding to the highest drug concentration. There was no increase in MIC for any strains following repeated exposure to naftifine hydrochloride. Naftifine hydrochloride demonstrated potent activity against all dermatophytes tested, and none of the isolates within this test panel demonstrated the potential for the development of resistance. Thus, future clinical studies of naftifine hydrochloride against dermatophytes may be warranted for the treatment of superficial dermatophytoses. PMID:23817365

Ghannoum, M; Isham, N; Verma, A; Plaum, S; Fleischer, A; Hardas, B

2013-09-01