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Sample records for antifungals myclobutanil propiconazole

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

    PubMed

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

    2005-11-01

    Over a 4 month brewing process, the fate of three fungicides, myclobutanil, propiconazole, and nuarimol, was studied in the spent grain, brewer wort, and final beer product. Only the residual level of myclobutanil after the mashing step was higher than its maximum residue limit (MRL) on barley. A substantial fraction was removed with the spent grain in all cases (26-42%). The half-life times obtained for the fungicides during storage of the spent grains ranged from 82 to 187 days. No significant influence of the boiling stage on the decrease of the fungicide residues was demonstrated. During fermentation, the content reduction varied from 20 to 47%. After the lagering and filtration steps, no significant decrease (<10%) was observed in any of the residues. Finally, during storage of the beer (3 months), the amounts of fungicides fell by 25-50% of their respective concentrations in the finished beer. PMID:16248555

  3. 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...

  4. 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...

  5. 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...

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

    EPA Science Inventory

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

  7. Propiconazole

    Integrated Risk Information System (IRIS)

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

  8. 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...

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

    PubMed

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

    2012-06-01

    According to its physical and chemical properties, the composition of difenoconazole/propiconazole microemulsion was as follows: xylene as solvent, emulsifier HSH as surfactant and methanol as cosurfactant. The optimal formulation of difenoconazole/propiconazole microemulsion was oil/SAA/water = 1/2/5 (w/w), in which the SAA consisted of emulsifier HSH and methanol with ratio of 3/2 (w/w). The cloud point of difenoconazole/propiconazole microemulsion was 70 degrees C and its effective ingredient content was 2.5% measured by High Performance Liquid Chromatography (HPLC). Its heat storage stability was studied according to the standards. The decomposition rates of the difenoconazole/propiconazole microemulsion were merely 2.45%, 2.63% respectively and met the Food and Agriculture Organization (FAO) standards of pesticide microemulsion. Investigated by Transmission Electron Microscopy (TEM) the particle size of difenoconazole/propiconazole microemulsion was 90-140 nm and its antifungal activities against Rhizoctonia solani AG1-IA were tested and compared with that of Meiyu. We found that the inhibition rates in the difenoconazole/propiconazole microemulsion treatment group were significantly higher than that of the emulsion group with the same content of effective ingredients and the study also revealed that its inhibiting ability on the formation and germination of sclerotia was significant. PMID:22822543

  10. 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...

  11. 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...

  12. 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...

  13. 78 FR 23497 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ...This regulation amends existing tolerances for residues of propiconazole in or on multiple commodities which are identified and discussed later in this document. Syngenta Crop Protection, LLC requested these tolerances under the Federal Food, Drug, and Cosmetic Act...

  14. 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...

  15. 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 (...

  16. 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...

  17. 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...

  18. 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...

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

    SciTech Connect

    Goetz, Amber K.; Dix, David J.

    2009-07-01

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

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

    PubMed

    Goetz, Amber K; Dix, David J

    2009-07-01

    The triazole antifungals myclobutanil, propiconazole and triadimefon cause varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in rodent in vivo models. To identify biological pathways consistently modulated across multiple timepoints and various study designs, gene expression profiling was conducted on rat livers from three separate studies with triazole treatment groups ranging from 6 h after a single oral gavage exposure, to prenatal to adult exposures via feed. To explore conservation of responses across species, gene expression from the rat liver studies were compared to in vitro data from rat and human primary hepatocytes exposed to the triazoles. Toxicogenomic data on triazoles from 33 different treatment groups and 135 samples (microarrays) identified thousands of probe sets and dozens of pathways differentially expressed across time, dose, and species--many of these were common to all three triazoles, or conserved between rodents and humans. Common and conserved pathways included androgen and estrogen metabolism, xenobiotic metabolism signaling through CAR and PXR, and CYP mediated metabolism. Differentially expressed genes included the Phase I xenobiotic, fatty acid, sterol and steroid metabolism genes Cyp2b2 and CYP2B6, Cyp3a1 and CYP3A4, and Cyp4a22 and CYP4A11; Phase II conjugation enzyme genes Ugt1a1 and UGT1A1; and Phase III ABC transporter genes Abcb1 and ABCB1. Gene expression changes caused by all three triazoles in liver and hepatocytes were concentrated in biological pathways regulating lipid, sterol and steroid homeostasis, identifying a potential common mode of action conserved between rodents and humans. Modulation of hepatic sterol and steroid metabolism is a plausible mode of action for changes in serum testosterone and adverse reproductive outcomes observed in rat studies, and may be relevant to human risk assessment. PMID:19409404

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

    PubMed

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

    2015-03-01

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

  2. PROPICONAZOLE-INDUCED CARCINOGENESIS: ROLE OF OXIDATIVE STRESS

    EPA Science Inventory

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

  3. Interaction of propiconazole in the peanut leafspot disease complex

    SciTech Connect

    Hancock, H.G.

    1985-01-01

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

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

    PubMed

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

    2016-01-01

    A 3-month-long experiment was conducted to ascertain the effects of different concentrations of myclobutanil (0.4 mg kg(-1) soil [T1]; 1.2 mg kg(-1) soil [T3]; and 4 mg kg(-1) soil [T10]) on soil microbial biomass, respiration, and soil nitrogen transformations using two typical agricultural soils (Henan fluvo-aquic soil and Shanxi cinnamon soil). Soil was sampled after 7, 15, 30, 60, and 90 days of incubation to determine myclobutanil concentration and microbial parameters: soil basal respiration (RB), microbial biomass carbon (MBC) and nitrogen (MBN), NO(-)3-N and NH(+)4-N concentrations, and gene abundance of total bacteria, N2-fixing bacteria, fungi, ammonia-oxidizing archaea (AOA), and ammonia-oxidizing bacteria (AOB). The half-lives of the different doses of myclobutanil varied from 20.3 to 69.3 d in the Henan soil and from 99 to 138.6 d in the Shanxi soil. In the Henan soil, the three treatments caused different degrees of short-term inhibition of RB and MBC, NH(+)4-N, and gene abundance of total bacteria, fungi, N2-fixing bacteria, AOA, and AOB, with the exception of a brief increase in NO(-)3-N content during the T10 treatment. The MBN (immobilized nitrogen) was not affected. In the Shanxi soil, MBC, the populations of total bacteria, fungi, and N2-fixing bacteria, and NH(+)4-N concentration were not significantly affected by myclobutanil. The RB and MBN were decreased transitorily in the T10 treatment. The NO(-)3-N concentrations and the abundance of both AOA and AOB were erratically stimulated by myclobutanil. Regardless of whether stimulation or suppression occurred, the effects of myclobutanil on the two soil types were short term. In summary, myclobutanil had no long-term negative effects on the soil microbial biomass, respiration, and soil nitrogen transformations in the two types of soil, even at 10-fold the recommended dosage. PMID:26590854

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

    EPA Science Inventory

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

  6. Acute toxicity, bioactivity, and enantioselective behavior with tissue distribution in rabbits of myclobutanil enantiomers.

    PubMed

    Sun, Mingjing; Liu, Donghui; Qiu, Xinxu; Zhou, Qian; Shen, Zhigang; Wang, Peng; Zhou, Zhiqiang

    2014-12-01

    The enantioselective bioactivity against pathogens (Cercospora arachidicola, Fulvia fulva, and Phytophthora infestans) and acute toxicity to Daphnia magna of the fungicide myclobutanil enantiomers were studied. The (+)-enantiomer in an antimicrobial activity test was about 1.79-1.96 times more active than the (-)-enantiomer. In the toxicity assay, the calculated 24-h LC50 values of the (-)-form, rac-form and (+)-form were 16.88, 13.17, and 11.91 mg/L, and the 48-h LC50 values were 10.15, 9.24, and 5.48 mg/L, respectively, showing that (+)-myclobutanil was more toxic. Meanwhile, the enantioselective metabolism of myclobutanil enantiomers following a single intravenous (i.v.) administration was investigated in rabbits. Total plasma clearance value (CL) of the (+)-enantiomer was 1.68-fold higher than its antipode. Significant differences in pharmacokinetics parameters between the two enantiomers indicated that the high bioactive (+)-enantiomer was preferentially metabolized and eliminated in plasma. Consistent consequences were found in the tissues (liver, brain, heart, kidney, fat, and muscle), resulting in a relative enrichment of the low-activity (-)-myclobutanil. These systemic assessments of the stereoisomers of myclobutanil cannot be used only to investigate environmental and biological behavior, but also have human health implications because of the long persistence of triazole fungicide and enantiomeric enrichment in mammals and humans. PMID:25043148

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

    USGS Publications Warehouse

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

    2011-01-01

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

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

    PubMed

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

    2011-11-23

    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 μg/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

  9. Antifungal polypeptides

    DOEpatents

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

    2009-09-15

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

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

    EPA Science Inventory

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

  11. 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...

  12. 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...

  13. 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 ...

  14. 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...

  15. 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...

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2001-03-01

    Propiconazole is a fungicide used in a variety of agricultural applications. Preliminary studies had suggested that embryos of the crustacean Daphnia magna are particularly susceptible to the toxicity of this chemical. The goals of the present study were to define endpoints of daphnid embryonic development that could be routinely used to assess the embryo toxicity of chemicals and to characterize definitively the embryo toxicity of propiconazole to daphnids. Daphnid embryonic development was characterized into six readily distinguishable stages based on the degree of tissue differentiation. Embryonic development could be monitored either in the brood chamber of the maternal organism or using embryos removed from the brood chamber and incubated ex vivo. Standard toxicity assessment revealed that propiconazole elicited no significant adverse effects on daphnid survival or fecundity during a 21-d exposure to concentrations as high as 0.25 mg/L. Exposure to 0.25 mg/L propiconazole, however, caused a significant incidence of developmental abnormalities and embryonic death. Abnormalities were consistent with developmental arrest at later stages of embryonic maturation. Propiconazole elicited a steep concentration-response curve with respect to embryo toxicity, with a 10% and a 90% incidence of embryo toxicity measured at 0.50 and 0.82 mg/L, respectively. Direct exposure of embryos to propiconazole resulted in toxicity, though the incidence and characteristics of developmental abnormalities were not consistent with that observed during chronic exposures. However, maternal exposure to propiconazole followed by transfer of early embryos to propiconazole-free media resulted in embryo toxicity consistent with that observed during chronic exposure. These results indicate that propiconazole interferes with the later stages of daphnid embryonic development, and that this toxicity is manifested largely via maternal exposure to the fungicide. PMID:11349850

  18. 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...

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

    EPA Science Inventory

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

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

    PubMed

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

    2014-07-01

    A high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method was developed for determining degradation dynamics and final residues of myclobutanil 25% WG in ginseng root, stem, leaf and soil. The samples were extracted with acetonitrile, cleaned-up with primary secondary amine (PSA) solid phase extraction cartridge, separated by Kromasil Eternity-5-C18 (2.1 mm x 150 mm, 5 microm) column with a gradient of acetonitrile and 0.1% formate in water as mobile phases, and analyzed with the multiple reaction monitoring (MRM) in positive ion mode by employing the external standard method. The average recoveries and the relative standard derivations (RSDs) of myclobutanil at the spiked level of 0.01-0.20 mg x kg(-1) were 80.9%-90.7% and 5.54%-9.29%, respectively, and the limit of quantification (LOQ) was 0.005 mg x kg(-1). The method with good reproducible, high precision and low detection limit could meet the requirements of residual analysis on ginseng production. The half-lives of myclobutanil were from 6.25 days to 9.94 days in ginseng root, stem, leaf and soil at spraying dosage of 1 152 g x hm(-2) The final residues were below 0.060 1 mg x kg(-1) in root, below 0.081 7 mg x kg(-1) in stem, 0.006 0-0.102 2 mg x kg(-1) in leaf and below 0.037 6 mg x kg(-1) in soil at spraying dosage range from 576 to 1 152 g x hm(-2). It is recommended that the MRLs of myclobutanil in dried ginseng may be suggested to be 0.10 mg x kg(-1) temporarily, and the preharvest interval was set at 35 days. PMID:25276964

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

    PubMed

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

    2016-05-01

    We carried out the biochemical evaluation of the target site of propiconazole in BR biosynthesis. Applying BR biosynthesis intermediates to Arabidopsis seedlings grown in the presence of propiconazole under dark condition, we found that the target site of propiconazole in BR biosynthesis can be identified among the C22 and C23 side chain hydroxylation steps from campestanol to teasterone. Using differential spectra techniques to determine the binding affinity of propiconazole to CYP90D1, which is responsible for C23 hydroxylation of BR, we found that propiconazole induced typical type II binding spectra in response to purified recombinant CYP90D1 and the Kd value was found approximately 0.76 μM. PMID:26987039

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

    PubMed

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

    2014-07-30

    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 γ1 (rarγ1) 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

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

    PubMed

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

    2013-04-01

    Conazoles are designed to inhibit cytochrome P450 (CYP) 14α-demethylase, an enzyme key to fungal cell wall formation. In vertebrates, conazoles may inhibit other CYPs, potentially disrupting processes like sex steroid synthesis. Propiconazole is a current-use pesticide that is among the first chemicals being tested in the U.S. Environmental Protection Agency endocrine disruptor screening program. Fathead minnows (Pimephales promelas) were exposed to 0, 5, 50, 500, or 1000 µg propiconazole/l in a 21-day study that evaluated apical reproductive endpoints (fecundity, fertility, hatch); measures of endocrine function and steroid synthesis, such as cholesterol, vitellogenin (VTG), and sex steroid (testosterone [T], 17β-estradiol [E2]) concentrations in the plasma; and changes in gonadal expression of steroidogenic genes. Plasma E2 and VTG concentrations in females were reduced by exposure to propiconazole, and egg production was decreased in the 500 and 1000 µg/l treatment groups. These in vivo effects coincided with inhibition of E2 synthesis by ovary explants exposed to propiconazole in vitro. We also observed a compensatory response in females exposed to propiconazole, manifested as increased gonad weight and upregulation of genes coding for key steriodogenic proteins, including CYP19 (aromatase), CYP17 (hydroxylase/lyase), CYP11A (cholesterol side-chain-cleavage), and steroidogenic acute regulatory protein. Other than an increase in relative testis weight, effects on endocrine function in males were less pronounced than in females. This study provides important data relative to the potential endocrine activity of propiconazole in fish and, more generally, to the further delineation of pathways for the reproductive effects of steroid synthesis inhibitors in fish. PMID:23339182

  4. Antifungal hydrogels

    PubMed Central

    Zumbuehl, Andreas; Ferreira, Lino; Kuhn, Duncan; Astashkina, Anna; Long, Lisa; Yeo, Yoon; Iaconis, Tiffany; Ghannoum, Mahmoud; Fink, Gerald R.; Langer, Robert; Kohane, Daniel S.

    2007-01-01

    Fungi are increasingly identified as major pathogens in bloodstream infections, often involving indwelling devices. Materials with antifungal properties may provide an important deterrent to these infections. Here we describe amphogel, a dextran-based hydrogel into which amphotericin B is adsorbed. Amphogel kills fungi within 2 h of contact and can be reused for at least 53 days without losing its effectiveness against Candida albicans. The antifungal material is biocompatible in vivo and does not cause hemolysis in human blood. Amphogel inoculated with C. albicans and implanted in mice prevents fungal infection. Amphogel also mitigates fungal biofilm formation. An antifungal matrix with these properties could be used to coat a variety of medical devices such as catheters as well as industrial surfaces. PMID:17664427

  5. 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...

  6. 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...

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

    EPA Science Inventory

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

  8. 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...

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2008-03-01

    Quantitative methods to measure dermal and inhalation exposure to the fungicide propiconazole were developed in the laboratory and applied in the occupational exposure setting for monitoring five farm workers' exposure during pesticide preparation and application to peach crops. Dermal exposure was measured with tape-strips applied to the skin, and the amount of propiconazole was normalized to keratin content in the tape-strip. Inhalation exposure was measured with an OVS tube placed in the worker's breathing-zone during pesticide handling. Samples were analyzed by GC-MS in EI+ mode (limit of detection 6 pg microl(-1)). Dermal exposure ranged from non-detectable to 32.1 +/- 22.6 ng per microg keratin while breathing-zone concentrations varied from 0.2 to 2.2 microg m(-3). A positive correlation was observed between breathing-zone concentrations and ambient air temperature (r2 = 0.87, p < 0.01). Breathing-zone concentrations did not correlate with dermal exposure levels (r2 = 0.11, p = 0.52). Propiconazole levels were below limit of detection when rubber gloves, coveralls, and full-face mask were used. The total-body propiconazole dose, determined for each worker by summing the estimated dermal dose and inhalation dose, ranged from 0.01 to 12 microg per kg body weight per day. Our results show that tape-stripping of the skin and the OVS can be effectively utilized to measure dermal and inhalation exposure to propiconazole, respectively, and that the dermal route of exposure contributed substantially more to the total dose than the inhalation route. PMID:18392276

  11. 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 ...

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

    PubMed

    Mohapatra, Soudamini

    2016-03-01

    Residue dynamics of difenoconazole and propiconazole on pomegranate was studied after application at the recommended and double doses of 125 and 250 g active ingredient (a.i.) ha(-1) during August-October 2012. The study was repeated during the same period in 2013. QuEChERS method, in conjunction with gas chromatography (GC), was used for analysis of the fungicides after carrying out the method validation. The recoveries of the fungicides from pomegranate and soil were between 80.3 and 96.2 %; the limit of detection (LOD) and limit of quantification (LOQ) were 0.016 and 0.05 mg kg(-1), respectively. The uncertainties of measurement were between 9.7 and 16.3 %. The initial residue deposits of difenoconazole were 0.875 and 1.205 mg kg(-1) from treatment at the recommended dose and 1.54 and 1.672 mg kg(-1) from treatment at the double dose from the first- and second-year studies. Propiconazole residues were 0.663 and 0.864 mg kg(-1) from recommended dose treatments and 1.474 and 2.045 mg kg(-1) from double dose treatments from the first- and second-year studies. The half-lives of degradation of difenoconazole were 6.4-8.4 days and propiconazole 7.9-8.5 days over the 2 years. Residues of difenoconazole and propiconazole remained on the pomegranate fruit surface and did not move to the edible part (aril). The pre-harvest intervals (PHIs), the time required for the residues to reduce below their respective EU maximum residue limits (MRLs), were 25.4 and 30.8 days for difenoconazole and 33.3 and 43.8 days for propiconazole from treatments at the recommended and double doses, respectively. Keeping in view consumer safety, the longer PHI from the two studies has been selected. PMID:26590055

  13. Antifungal agents.

    PubMed

    Ryder, N S

    1999-12-01

    At this year's ICAAC Meeting, new data on approximately 20 different antifungal agents were presented, while no new agents were disclosed. Drugs in late development include the triazoles, voriconazole (Pfizer Ltd) and Sch-56592 (Schering-Plough Corp), and the echinocandins, caspofungin (Merck & Co Inc) and FK-463 (Fujisawa Pharmaceutical Co Ltd). In contrast to previous years, presentations on these and earlier developmental compounds were relatively modest in scope, with few significant new data. Little new information appeared on the most recent novel class of agents, the sordarins (Glaxo Wellcome plc). Early clinical results were presented for FK-463, showing acceptable tolerability and dose-dependent efficacy in AIDS-associated esophageal candidiasis. A new liposomal formulation of nystatin (Nyotran; Aronex Pharmaceuticals Inc) was shown to be equivalent to conventional amphotericin B in empiric therapy of presumed fungal infection in neutropenic patients, but with reduced toxicity. Intravenous itraconazole (Janssen Pharmaceutica NV) was an effective prophylactic therapy in invasive pulmonary aspergillosis, while oral itraconazole was discussed as a treatment for fungal infection in heart and liver transplant patients. The allylamine compound, terbinafine (Novartis AG), showed good clinical efficacy against fungal mycetoma, a serious tropical infection. A major highlight was the first presentation of inhibitors of fungal efflux pumps as a strategy for overcoming resistance. MC-510027 (milbemycin alpha-9; Microcide Pharmaceuticals Inc) and its derivatives, potentiated the antifungal activity of triazoles and terbinafine in a number of Candida spp. Another pump inhibitor, MC-005172 (Microcide Pharmaceuticals Inc) showed in vivo potentiation of fluconazole in a mouse kidney infection model. Microcide Pharmaceuticals Inc also presented inhibitors of bacterial efflux pumps. PMID:16113946

  14. 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 ...

  15. 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...

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

    PubMed

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

    2016-03-01

    Fungicidal active ingredients azoxystrobin and propiconazole, individually and in combination, have been marketed worldwide in a range of fungicide treatment products for preventative and curative purposes, respectively. Their presence in streams located throughout the midwestern and southeastern United States warrant the need for research into the potential routes of transport of these fungicides in an agricultural field setting. Potential canopy penetration and drift effects of these fungicides during aerial and ground applications were studied in the current project. Canopy penetration was observed for both application types, however drift was associated only with the aerial application of these fungicides. Azoxystrobin and propiconazole persisted in the soil up to 301 d, with peak concentrations occurring approximately 30 d after application. The predominant mode of transport for these compounds was agricultural runoff water, with the majority of the fungicidal active ingredients leaving the target area during the first rain event following application. The timing of application in relation to the first rain event significantly affected the amount of loss that occurred, implying application practices should follow manufacturer recommended guidelines. PMID:26741551

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Pediatric Antifungal Agents

    PubMed Central

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

    2009-01-01

    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. PMID:19741525

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

    SciTech Connect

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

    2012-04-15

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

  20. Triazole antifungals: a review.

    PubMed

    Peyton, L R; Gallagher, S; Hashemzadeh, M

    2015-12-01

    Invasive fungal infections and systemic mycosis, whether from nosocomial infection or immunodeficiency, have been on an upward trend for numerous years. Despite advancements in antifungal medication, treatment in certain patients can still be difficult for reasons such as impaired organ function, limited administration routes or poor safety profiles of the available antifungal medications. The growing number of invasive fungal species becoming resistant to current antifungal medications is of appreciable concern. Triazole compounds containing one or more 1,2,4-triazole rings have been shown to contain some of the most potent antifungal properties. Itracon-azole and fluconazole were some of the first triazoles synthesized, but had limitations associated with their use. Second-generation triazoles such as voriconazole, posa-conazole, albaconazole, efinaconazole, ravuconazole and isavuconazole are all derivatives of either itraconazole or fluconazole, and designed to overcome the deficiencies of their parent drugs. The goal of this manuscript is to review antifungal agents derived from triazole. PMID:26798851

  1. Antifungal Compounds from Cyanobacteria

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-03-01

    In this study, the toxic effects of propiconazole (PCZ), a triazole fungicide present in aquatic environment, were studied in juvenile rainbow trout, Oncorhynchus mykiss, by acute toxicity test with the concentration of 5.04 mg/L (96 h LC50). Morphological indices, hematological parameters, liver xenobiotic-metabolizing response, and tissue antioxidant status were evaluated. Compared with the control group, fish exposed to PCZ showed significantly higher Leuko, PCV, MCHC, and hepatic EROD, and significantly lower MCV. CF and HSI were not significantly different among groups. SOD, CAT, GPx, and GR activities increased significantly in liver of experimental groups, but decreased significantly in gill. In general, antioxidant enzyme activity in intestine was less evident than in liver. Oxidative stress indices (levels of LPO and CP) were significantly higher in gill. Additionally, through chemometrics of all parameters measured in this study, two groups with 67.29% of total accumulated variance were distinguished. In short, the physiological and biochemical responses in different tissues of fish indicated that PCZ-induced the stressful environmental conditions. But according to PCZ residual status in the natural environment, more long-term experiments at lower concentrations will be necessary in the future. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013. PMID:21384499

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

    PubMed Central

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

    2011-01-01

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

  4. New antifungal agents.

    PubMed

    Gupta, Aditya K; Tomas, Elizabeth

    2003-07-01

    Currently, use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. New formulations are being prepared to improve absorption and efficacy of some of these standard therapies. Various new antifungals have demonstrated therapeutic potential. These new agents may provide additional options for the treatment of superficial fungal infections and they may help to overcome the limitations of current treatments. Liposomal formulations of AmB have a broad spectrum of activity against invasive fungi, such as Candida spp., C. neoformans, and Aspergillus spp., but not dermatophyte fungi. The liposomal AmB is associated with significantly less toxicity and good rates of efficacy, which compare or exceed that of standard AmB. These factors may provide enough of an advantage to patients to overcome the increased costs of these formulations. Three new azole drugs have been developed, and may be of use in both systemic and superficial fungal infections. Voriconazole, ravuconazole, and posaconazole are triazoles, with broad-spectrum activity. Voriconazole has a high bioavailability, and has been used with success in immunocompromised patients with invasive fungal infections. Ravuconazole has shown efficacy in candidiasis in immunocompromised patients, and onychomycosis in healthy patients. Preliminary in vivo studies with posaconazole indicated potential use in a variety of invasive fungal infections including oropharyngeal candidiasis. Echinocandins and pneumocandins are a new class of antifungals, which act as fungal cell wall beta-(1,3)-D-glucan synthase enzyme complex inhibitors. Caspofungin (MK-0991) is the first of the echinocandins to receive Food and Drug Administration approval for patients with invasive aspergillosis not responding or intolerant to other antifungal therapies, and has been effective in patients with oropharyngeal and esophageal candidiasis. Standardization of MIC value determination has improved the

  5. 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...

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

    PubMed

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

    2016-01-01

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

  7. 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 ...

  8. EUCAST breakpoints for antifungals.

    PubMed

    Rodríguez-Tudela, Juan L; Arendrup, Maiken C; Cuenca-Estrella, Manuel; Donnelly, J Peter; Lass-Flörl, Cornelia

    2010-03-01

    Susceptibility testing of fungi and development of interpretative breakpoints has become increasingly important due to the growing incidence of invasive fungal infections, the number and classes of antifungals, and the emerging reports of acquired resistance. The subcommittee on antifungal susceptibility testing of the European Committee on Antibiotic Susceptibility Testing (EUCAST) has developed standards for susceptibility testing of fermentative yeasts and molds as well as proposing breakpoints for fluconazole and voriconazole against Candida. The aim of this work is to describe the EUCAST process of setting breakpoints for antifungals. Five aspects are evaluated during the process of developing breakpoints: 1) the most common dosage used in each European country, 2) the definition of the wild-type population for each target microorganism at the species level and the determination of epidemiological cutoffs, 3) the drug's pharmacokinetics and 4) pharmacodynamics, including Monte Carlo simulations, and 5) the correlation of MICs with clinical outcome of patients treated with the compound. When insufficient data are available (e.g., due to lack of information on the clinical outcome of infections caused by isolates with an elevated MIC), epidemiological cutoff values, rather than breakpoints, are recommended until the necessary information becomes available. PMID:20369073

  9. Tissue Penetration of Antifungal Agents

    PubMed Central

    Felton, Timothy; Troke, Peter F.

    2014-01-01

    SUMMARY Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection. PMID:24396137

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

    PubMed

    Gupta, Deepa; Jain, D K

    2015-01-01

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

  11. Update on azole antifungals.

    PubMed

    Zonios, Dimitrios I; Bennett, John E

    2008-04-01

    This is a comprehensive, clinically oriented review of the four commercially available triazoles: fluconazole, itraconazole, voriconazole, and posaconazole. Emphasis is placed in pharmacology, drug interactions, adverse events, antifungal activity, and the evolving perspective of their clinical use. Key clinical trials are briefly discussed, and specific drug indications summarized. Fluconazole remains a valuable low-cost choice for the treatment of various fungal infections, including candidiasis and cryptococcosis. It has relatively few drug interactions and is safe but lacks activity against filamentous fungi. The use of itraconazole is historically plagued by erratic bioavailability of the oral capsule, improved with the oral solution. Drug interactions are numerous. Itraconazole exhibits significant activity against Aspergillus and the endemic fungi. Voriconazole has revolutionized the treatment of aspergillosis in severely immunocompromised patients, but its use is compromised by complicated pharmacokinetics, notable drug interactions, and relatively significant adverse events. Finally, posaconazole is the last addition to the azole armamentarium with extended antifungal spectrum, significant activity against the zygomycetes, and, apparently, optimal safety profile. Posaconazole has a significant role for the prophylaxis of invasive fungal infections in severely immunocompromised patients. Multiple daily dosing, a need for fatty foods for absorption, and absence of an intravenous formulation restrict its use to selected populations. PMID:18366001

  12. Recent advances in antifungal chemotherapy.

    PubMed

    Petrikkos, George; Skiada, Anna

    2007-08-01

    For over 50 years, amphotericin B deoxycholate (AmBD) has been the 'gold standard' in antifungal chemotherapy, despite its frequent toxicities. However, improved treatment options for invasive fungal infections (IFIs) have been developed during the last 15 years. Newer antifungal agents, including less toxic lipid preparations of AmBD, triazoles and the echinocandins, have been added to our armamentarium against IFIs. Some of these newer drugs can now replace AmBD as primary therapy (e.g. caspofungin for candidiasis, voriconazole for aspergillosis), whilst others offer new therapeutic options for difficult-to-treat IFIs (e.g. posaconazole for zygomycosis, fusariosis and chromoblastomycosis). It is interesting that extended use of newer antifungals such as fluconazole, despite decreasing the mortality attributed to candidiasis, resulted in selection of species resistant to several antifungals (Candida krusei, Candida glabrata); whilst several publications suggest that prolonged use of voriconazole may expose severely immunocompromised patients to the risk of zygomycosis (breakthrough). On the other hand, the differences in the mode of action of newer antifungals such as echinocandins raise the question whether combination antifungal therapy is more effective than monotherapy. Finally, the availability of an oral formulation with excellent biosafety of several newer antifungals (e.g. posaconazole) makes them candidates for prophylactic or prolonged maintenance therapy. PMID:17524625

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

    EPA Science Inventory

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

  14. 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...

  15. 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...

  16. 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 ...

  17. 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...

  18. 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-...

  19. 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 ...

  20. 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 ...

  1. Suppressive drug interactions between antifungals.

    PubMed

    de Vos, Marjon G J; Bollenbach, Tobias

    2014-04-24

    In this issue of Chemistry & Biology, Cokol and colleagues report a systematic study of drug interactions between antifungal compounds. Suppressive drug interactions occur more frequently than previously realized and come in different flavors with interesting implications. PMID:24766845

  2. Antifungal therapy with an emphasis on biofilms

    PubMed Central

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

    2013-01-01

    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

  3. Comparison of echinocandin antifungals

    PubMed Central

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

    2007-01-01

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

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

    PubMed

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

    2015-05-01

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

  5. Alternative approaches to antifungal therapies

    PubMed Central

    Mehra, T; Köberle, M; Braunsdorf, C; Mailänder-Sanchez, D; Borelli, C; Schaller, M

    2012-01-01

    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. PMID:23078400

  6. Haloprogin: a Topical Antifungal Agent

    PubMed Central

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

    1970-01-01

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

  7. Antifungal Compounds from Piper Species

    PubMed Central

    Xu, Wen-Hui; Li, Xing-Cong

    2013-01-01

    This review documents chemical structures and antifungal activities of 68 compounds isolated from 22 Piper species of the plant family Piperaceae. These compounds include amides, flavonoids, prenylated benzoic acid derivatives, lignans, phenylpropanoids, butenolides, and cyclopentendiones. Some of them may serve as leads for potential pharmaceutical or agricultural fungicide development. PMID:24307889

  8. Antifungal activity of juniper extracts

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

    Elmholt, S

    1991-12-01

    The present study was performed as a dose-response field experiment using a trade marked formulation of the ergosterol biosynthesis inhibiting fungicide, propiconazole, applied at the recommended and ten times the recommended application rates. The soil 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 period from May 22 to August 11, 1986. The numbers of yeasts and filamentous fungi were enumerated, the latter includingCladosporium andPenicillium, which were also enumerated separately. The fluctuations in fungal occurrence due to the propiconazole treatment were smaller than seasonal fluctuations, these most likely being caused by variations in the soil matric potential and by soil invasion of phyllosphere fungi. Fungicide treatment had significant inhibitory effects on the filamentous fungi, especially on theCladosporium, whereas no significant effects were found on the yeasts and onPenicillium spp. From an ecotoxicological point of view, it is important that the effects were considerably delayed, with respect to the time of fungicide application. PMID:24194329

  10. A Prototype Antifungal Contact Lens

    PubMed Central

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

    2011-01-01

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

  11. Advancements in Topical Antifungal Vehicles.

    PubMed

    Kircik, Leon H

    2016-02-01

    The primary treatment for superficial fungal infections is antifungal topical formulations, and allylamines and azoles represent the two major classes of topical formulations that are used to treat these infections. The stratum corneum (SC) is composed of keratinocytes that are surrounded by a matrix of lipids. The efficacy of topically applied formulations depends on their ability to penetrate this lipid matrix, and the vehicle plays an integral role in the penetration of active molecule into skin. There are several challenges to formulating topical drugs, which include the biotransformation of the active molecules as they pass through the SC and the physical changes that occur to the vehicle itself when it is applied to the skin. This article will review current and emerging topical antifungal vehicles. PMID:26885798

  12. Antifungal stilbenoids from Stemona japonica.

    PubMed

    Zhang, Ya-Zhong; Xu, Guo-Bing; Zhang, Tong

    2008-01-01

    Three new dihydrostilbenes, stilbostemins P-R (1-3), and a new dihydrophenanthrene, stemanthrene G (4), were isolated from the roots of Stemona japonica together with three known bibenzyls, 3,5-dihydroxy-2'-methoxy bibenzyl (5), 3,3'-dihydroxy-2,5'-dimethoxy bibenzyl (6), and 3,5,2'-trihydroxy-4-methyl bibenzyl (7). Their structures were elucidated by spectroscopic analyses. Compounds 5 and 6 exhibited strong antifungal activities against Candida albicans. PMID:18636375

  13. Defensins: antifungal lessons from eukaryotes

    PubMed Central

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

    2014-01-01

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

  14. Evaluation of vaginal antifungal formulations in vivo.

    PubMed Central

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

    1979-01-01

    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. PMID:392480

  15. Antibacterial and Antifungal Compounds from Marine Fungi

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

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

    2014-01-01

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

  18. Antifungals: Mechanism of Action and Drug Resistance.

    PubMed

    Prasad, Rajendra; Shah, Abdul Haseeb; Rawal, Manpreet Kaur

    2016-01-01

    There are currently few antifungals in use which show efficacy against fungal diseases. These antifungals mostly target specific components of fungal plasma membrane or its biosynthetic pathways. However, more recent class of antifungals in use is echinocandins which target the fungal cell wall components. The availability of mostly fungistatic antifungals in clinical use, often led to the development of tolerance to these very drugs by the pathogenic fungal species. Thus, the development of clinical multidrug resistance (MDR) leads to higher tolerance to drugs and its emergence is helped by multiple mechanisms. MDR is indeed a multifactorial phenomenon wherein a resistant organism possesses several mechanisms which contribute to display reduced susceptibility to not only single drug in use but also show collateral resistance to several drugs. Considering the limited availability of antifungals in use and the emergence of MDR in fungal infections, there is a continuous need for the development of novel broad spectrum antifungal drugs with better efficacy. Here, we briefly present an overview of the current understanding of the antifungal drugs in use, their mechanism of action and the emerging possible novel antifungal drugs with great promise. PMID:26721281

  19. Natural and synthetic peptides with antifungal activity.

    PubMed

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

    2016-08-01

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

  20. Antifungal Activity of C-27 Steroidal Saponins

    PubMed Central

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

    2006-01-01

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

  1. Antifungal susceptibilities of Paecilomyces species.

    PubMed

    Aguilar, C; Pujol, I; Sala, J; Guarro, J

    1998-07-01

    The MICs and minimum fungicidal concentrations (MFCs) of amphotericin B, miconazole, itraconazole, ketoconazole, fluconazole, and flucytosine for 52 isolates of Paecilomyces species were evaluated by the broth microdilution method, largely based on the recommendations of the National Committee for Clinical Laboratory Standards (document M27-A). The fungal isolates tested included 16 P. variotii, 11 P. lilacinus, 9 P. marquandii, 6 P. fumosoroseus, 4 P. javanicus, and 2 P. viridis isolates and 1 isolate of each of the following species: P. carneus, P. farinosus, P. fulvus, and P. niveus. The MFCs and the MICs at which 90% of isolates were inhibited (MIC90s) for the six antifungal agents were remarkably high; the MIC50s indicated that amphotericin B, miconazole, itraconazole, and ketoconazole had good activities, while fluconazole and flucytosine demonstrated poor efficacy. The ranges of the MICs were generally wider and lower than those of the MFCs. There were significant susceptibility differences among the species. All species with the exception of P. variotii were highly resistant to fluconazole and flucytosine; P. variotii was susceptible to flucytosine. Amphotericin B and the rest of the azoles showed good activity against P. variotii, while all the antifungal agents assayed showed low efficacy against P. lilacinus. PMID:9660991

  2. Antifungal Susceptibilities of Paecilomyces Species

    PubMed Central

    Aguilar, C.; Pujol, I.; Sala, J.; Guarro, J.

    1998-01-01

    The MICs and minimum fungicidal concentrations (MFCs) of amphotericin B, miconazole, itraconazole, ketoconazole, fluconazole, and flucytosine for 52 isolates of Paecilomyces species were evaluated by the broth microdilution method, largely based on the recommendations of the National Committee for Clinical Laboratory Standards (document M27-A). The fungal isolates tested included 16 P. variotii, 11 P. lilacinus, 9 P. marquandii, 6 P. fumosoroseus, 4 P. javanicus, and 2 P. viridis isolates and 1 isolate of each of the following species: P. carneus, P. farinosus, P. fulvus, and P. niveus. The MFCs and the MICs at which 90% of isolates were inhibited (MIC90s) for the six antifungal agents were remarkably high; the MIC50s indicated that amphotericin B, miconazole, itraconazole, and ketoconazole had good activities, while fluconazole and flucytosine demonstrated poor efficacy. The ranges of the MICs were generally wider and lower than those of the MFCs. There were significant susceptibility differences among the species. All species with the exception of P. variotii were highly resistant to fluconazole and flucytosine; P. variotii was susceptible to flucytosine. Amphotericin B and the rest of the azoles showed good activity against P. variotii, while all the antifungal agents assayed showed low efficacy against P. lilacinus. PMID:9660991

  3. Active packaging with antifungal activities.

    PubMed

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

    2016-03-01

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

  4. Antifungal proteins: More than antimicrobials?

    PubMed Central

    Hegedüs, Nikoletta; Marx, Florentine

    2013-01-01

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

  5. Antifungal isopimaranes from Hypoestes serpens.

    PubMed

    Rasoamiaranjanahary, L; Guilet, D; Marston, A; Randimbivololona, F; Hostettmann, K

    2003-09-01

    Five isopimarane diterpenes (7beta-hydroxyisopimara-8,15-dien-14-one, 14alpha-hydroxyisopimara-7,15-dien-1-one, 1beta,14alpha-dihydroxyisopimara-7,15-diene, 7beta-hydroxyisopimara-8(14),15-dien-1-one and 7beta-acetoxyisopimara-8(14),15-dien-1-one) have been isolated from the leaves of Hypoestes serpens (Acanthaceae). All compounds exhibited antifungal activity against both the plant pathogenic fungus Cladosporium cucumerinum and the yeast Candida albicans; two of them also displayed an acetylcholinesterase inhibition. The structures of the compounds were determined by means of spectrometric methods, including 1D and 2D NMR experiments and MS analysis. PMID:12943772

  6. Topical antifungals for seborrhoeic dermatitis

    PubMed Central

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

    2015-01-01

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

  7. Early state research on antifungal natural products.

    PubMed

    Negri, Melyssa; Salci, Tânia P; Shinobu-Mesquita, Cristiane S; Capoci, Isis R G; Svidzinski, Terezinha I E; Kioshima, Erika Seki

    2014-01-01

    Nosocomial infections caused by fungi have increased greatly in recent years, mainly due to the rising number of immunocompromised patients. However, the available antifungal therapeutic arsenal is limited, and the development of new drugs has been slow. Therefore, the search for alternative drugs with low resistance rates and fewer side effects remains a major challenge. Plants produce a variety of medicinal components that can inhibit pathogen growth. Studies of plant species have been conducted to evaluate the characteristics of natural drug products, including their sustainability, affordability, and antimicrobial activity. A considerable number of studies of medicinal plants and alternative compounds, such as secondary metabolites, phenolic compounds, essential oils and extracts, have been performed. Thus, this review discusses the history of the antifungal arsenal, surveys natural products with potential antifungal activity, discusses strategies to develop derivatives of natural products, and presents perspectives on the development of novel antifungal drug candidates. PMID:24609016

  8. 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...

  9. Antifungal drug discovery: the process and outcomes

    PubMed Central

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

    2014-01-01

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

  10. New Antifungal Pyranoisoflavone from Ficus tikoua Bur.

    PubMed Central

    Wei, Shaopeng; Wu, Wenjun; Ji, Zhiqin

    2012-01-01

    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 μg·mL−1, respectively. PMID:22837700

  11. Antifungal drug discovery: the process and outcomes.

    PubMed

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

    2014-01-01

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

  12. Synthesis, Antifungal Activities and Qualitative Structure Activity Relationship of Carabrone Hydrazone Derivatives as Potential Antifungal Agents

    PubMed Central

    Wang, Hao; Ren, Shuang-Xi; He, Ze-Yu; Wang, De-Long; Yan, Xiao-Nan; Feng, Jun-Tao; Zhang, Xing

    2014-01-01

    Aimed at developing novel fungicides for relieving the ever-increasing pressure of agricultural production caused by phytopathogenic fungi, 28 new hydrazone derivatives of carabrone, a natural bioactive sesquisterpene, in three types were designed, synthesized and their antifungal activities against Botrytis cinerea and Colletotrichum lagenarium were evaluated. The result revealed that all the derivatives synthesized exhibited considerable antifungal activities in vitro and in vivo, which led to the improved activities for carabrone and its analogues and further confirmed their potential as antifungal agents. PMID:24619221

  13. Antifungal activity of five species of Polygala

    PubMed Central

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

    2011-01-01

    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 μg/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 μg/mL and 250 μg/mL, respectively) and C. gattii (both with MICs of 250 μg/mL). Rutin and aurapten isolated from P. paniculata showed antifungal activity against C. gattii with MIC values of 60 and 250 μg/mL, respectively. In the antifungal screening, few of the isolated compounds showed good antifungal inhibition. The compound α-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. PMID:24031724

  14. Screening antifungal activities of selected medicinal plants.

    PubMed

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

    2001-01-01

    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

  15. Outcome of empirical or targeted antifungal therapy after antifungal prophylaxis in febrile neutropenia.

    PubMed

    Hahn-Ast, C; Felder, L; Mayer, K; Mückter, S; Ruhnke, M; Hein, R; Hellmich, M; Schwab, K; Rachow, T; Brossart, P; von Lilienfeld-Toal, M

    2016-05-01

    Azole prophylaxis has been shown to be effective in preventing invasive fungal infections (IFIs) and increasing survival in patients with prolonged neutropenia after myelosuppressive chemotherapy for haematological malignancies. Similarly, empirical antifungal therapy for persistent neutropenic fever has been shown to reduce IFI-related mortality. However, to date, there is little information with regard to the outcome of patients who receive both strategies. Here, we present our retrospective data on three cohorts of patients receiving empirical or targeted antifungal therapy after different antifungal prophylaxis regimens. All records from patients who received myelosuppressive induction chemotherapy for acute myelogenous leukemia (AML) in our centre from 2004-2010 were analysed. From 2004-2006, itraconazole was used as antifungal prophylaxis; for the first 6 months in 2007, local polyenes and from mid-2007 till 2010, posaconazole. Data of 315 courses of chemotherapy in 211 patients were analysed. Antifungal therapy (empirical or targeted, time point and antifungal agent at the physician's discretion) was initiated in 50/174 (29 %), 7/18 (39 %) and 34/123 courses (28 %, p = 0.615) in the itra cohort, the cohort without systemic prophylaxis and the posa cohort, respectively, and was effective in 24/50 (48 %), 5/7 (71 %) and 22/34 courses (65 %, p = 0.221), respectively. IFI occurred in 25/174 (14 %), 4/18 (22 %) and 16/123 (13 %) courses, respectively (p = 0.580). IFI-related survival was not different in the three cohorts. Antifungal treatment in patients with AML who received azole prophylaxis resulted in the expected efficacy-importantly, prior posaconazole prophylaxis did not render subsequent antifungal treatment less effective than prior itraconazole prophylaxis. PMID:27021301

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

    PubMed

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

    2016-07-01

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

  17. Efflux-Mediated Antifungal Drug Resistance†

    PubMed Central

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

    2009-01-01

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

  18. Synthetic Multivalent Antifungal Peptides Effective against Fungi

    PubMed Central

    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

    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

  19. Antifungal effect of some spice hydrosols.

    PubMed

    Boyraz, Nuh; Ozcan, Musa

    2005-12-01

    The antifungal effects of rosemary, cumin, sater (savory), basil and pickling herb hydrosols were investigated against Rhizoctonia solani, Fusarium oxysporum f. sp tulipae, Botrytis cinerea and Alternaria citri. Hydrosols of sater and pickling herb showed the most relevant fungicidal activity. PMID:16243447

  20. Antifungal prophylaxis during neutropenia and immunodeficiency.

    PubMed Central

    Lortholary, O; Dupont, B

    1997-01-01

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

  1. Oral Antifungal Drugs in the Treatment of Dermatomycosis.

    PubMed

    Tsunemi, Yuichiro

    2016-01-01

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

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

    PubMed

    Percival, Glynn C; Noviss, Kelly

    2008-11-01

    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

  3. From antidiabetic to antifungal: discovery of highly potent triazole-thiazolidinedione hybrids as novel antifungal agents.

    PubMed

    Wu, Shanchao; Zhang, Yongqiang; He, Xiaomeng; Che, Xiaoying; Wang, Shengzheng; Liu, Yang; Jiang, Yan; Liu, Na; Dong, Guoqiang; Yao, Jianzhong; Miao, Zhenyuan; Wang, Yan; Zhang, Wannian; Sheng, Chunquan

    2014-12-01

    In an attempt to discover a new generation of triazole antifungal agents, a series of triazole-thiazolidinedione hybrids were designed and synthesized by molecular hybridization of the antifungal agent fluconazole and rosiglitazone (an antidiabetic). Most of the target compounds showed good to excellent inhibitory activity against a variety of clinically important fungal pathogens. In particular, compounds (Z)-5-(2,4-dichlorobenzylidene)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)thiazolidine-2,4-dione) (15 c), (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15 j), and (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15 r) were highly active against Candida albicans, with MIC80 values in the range of 0.03-0.15 μM. Moreover, compounds 15 j and 15 r were found to be effective against four fluconazole-resistant clinical isolates; these two compounds are particularly promising antifungal leads for further optimization. Molecular docking studies revealed that the hydrogen bonding interactions between thiazolidinedione and CYP51 from C. albicans are important for antifungal activity. This study also demonstrates the effectiveness of molecular hybridization in antifungal drug discovery. PMID:25196996

  4. In vitro antifungal activity of topical and systemic antifungal drugs against Malassezia species.

    PubMed

    Carrillo-Muñoz, Alfonso Javier; Rojas, Florencia; Tur-Tur, Cristina; de Los Ángeles Sosa, María; Diez, Gustavo Ortiz; Espada, Carmen Martín; Payá, María Jesús; Giusiano, Gustavo

    2013-09-01

    The strict nutritional requirements of Malassezia species make it difficult to test the antifungal susceptibility. Treatments of the chronic and recurrent infections associated with Malassezia spp. are usually ineffective. The objective of this study was to obtain in vitro susceptibility profile of 76 clinical isolates of Malassezia species against 16 antifungal drugs used for topical or systemic treatment. Isolates were identified by restriction fragment length polymorphism. Minimal inhibitory concentrations (MIC) were obtained by a modified microdilution method based on the Clinical Laboratory Standards Institute reference document M27-A3. The modifications allowed a good growth of all tested species. High in vitro antifungal activity of most tested drugs was observed, especially triazole derivatives, except for fluconazole which presented the highest MICs and widest range of concentrations. Ketoconazole and itraconazole demonstrated a great activity. Higher MICs values were obtained with Malassezia furfur indicating a low susceptibility to most of the antifungal agents tested. Malassezia sympodialis and Malassezia pachydermatis were found to be more-susceptible species than M. furfur, Malassezia globosa, Malassezia slooffiae and Malassezia restricta. Topical substances were also active but provide higher MICs than the compounds for systemic use. The differences observed in the antifungals activity and interspecies variability demonstrated the importance to studying the susceptibility profile of each species to obtain reliable information for defining an effective treatment regimen. PMID:23496653

  5. Photodynamic therapy as an antifungal treatment

    PubMed Central

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

    2016-01-01

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

  6. Natural Killer Cells and Antifungal Host Response

    PubMed Central

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

    2013-01-01

    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. PMID:23365210

  7. Antifungal activity of 10 Guadeloupean plants.

    PubMed

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

    2013-11-01

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

  8. Econazole imprinted textiles with antifungal activity.

    PubMed

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

    2016-04-01

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

  9. [New antifungal agents: voriconazole and caspofungin].

    PubMed

    Dupont, B

    2003-12-01

    Among new available antifungal agents voriconazole is a new triazole with an intravenous (i.v.) and oral formulation, and caspofungin is an echinocandin, new family with a new mode of action on the cell wall. It is available as an i.v. preparation. Both drugs have a broad spectrum targeting most of the usual pathogens: Candida and Aspergillus, even with low suceptibility or resistance to other antifungals. Voriconazole is also active on Scedosporium and Fusarium. The efficacy of these molecules was established in vitro and in experimental infections in animals either normal or immunosuppressed. Voriconazole is active in oropharyngeal and esophageal candidiasis, in refractory invasive candidiasis and as a first line treatment of invasive aspergillosis with better results than amphotéricine B. It was also effective in scedosporiosis and in fusariosis. Caspofungin is active in oropharyngeal and esophageal candidiasis, in invasive candidiasis ranking among the best drugs in non neutropenic patients. It was shown effective in refractory aspergillosis. As empirical treatment of febrile neutropenic patients, these molecules should probably be restricted to the highest risk-population. Safety is good, side effects are a rare cause of discontinuation of treatment, class specific drug-drug interactions occur with voriconazole. These molecules open an important field of investigations with combination of antifungal agents. PMID:15022787

  10. Antifungal serum concentration monitoring: an update.

    PubMed

    Goodwin, Megan L; Drew, Richard H

    2008-01-01

    Invasive fungal infections (IFIs) are occurring with increasing incidence and are associated with significant morbidity and mortality. Understanding the relationship between the pharmacokinetic and pharmacodynamic properties of antifungals is essential to optimize the potential for favourable clinical and microbiological outcomes while minimizing risks of treatment-related toxicity. Antifungal serum concentrations may aid in the determination of appropriate dosing in select circumstances. The polyene and echinocandin classes of antifungals lack sufficient data to justify serum concentration monitoring in routine clinical practice. In contrast, serum concentration monitoring of flucytosine may help to reduce the risk of treatment-related haematological toxicity. Determination of itraconazole serum concentrations is advised in situations where the drug is used for prolonged periods to treat serious IFIs (such as invasive aspergillosis or histoplasmosis) because of variability in absorption following oral administration (most notable for the capsule formulation). The use of serum concentration monitoring during therapy with the extended-spectrum triazoles (i.e. voriconazole and posaconazole) is still evolving, due primarily to inter-patient variability in drug exposure combined with sparse data regarding relationships with efficacy (posaconazole) and both safety and efficacy (voriconazole). PMID:17999982

  11. Antifungal activity of Eugenia umbelliflora against dermatophytes.

    PubMed

    Machado, Karina E; Cechinel Filho, Valdir; Cruz, Rosana C B; Meyre-Silva, Christiane; Cruz, Alexandre Bella

    2009-09-01

    Antifungal activities of Eugenia umbelliflora Berg. (Myrtaceae) were tested in vitro against a panel of standard and clinical isolates of human fungal pathogens (dermatophytes and opportunistic saprobes). Methanol extracts of leaves and fruits of E. umbelliflora were separately prepared and partitioned, to yield dichloromethane (DCM), ethyl acetate (EtOAc) and aqueous fractions (Aq). Three compounds (1-3) were obtained from the DCM extract using chromatographic procedures. Antifungal assays were performed using agar dilution techniques. Both extracts (fruits and leaves), their DCM and EtOAc fractions, and compound 2 (betulin and betulinic acid) presented selective antifungal activity against dermatophytes (Epidermophyton floccosum, Microsporum canis, Microsporum gypseum, Trichophyton rubrum, Trichophyton mentagrophytes), with MIC values between 200 and 1000 microg/mL, and interestingly, inhibited 4/5 species with MIC values of < or = 500 microg/mL. The aqueous fractions of fruits and leaves, and compounds 1 (alpha, beta amyrin) and 3 (taraxerol) were inactive up to the maximum concentrations tested (1000 microg/mL). PMID:19831024

  12. Antifungal Activity of Maytenin and Pristimerin

    PubMed Central

    Gullo, Fernanda P.; Sardi, Janaina C. O.; Santos, Vânia A. F. F. M.; Sangalli-Leite, Fernanda; Pitangui, Nayla S.; Rossi, Suélen A.; de Paula e Silva, Ana C. A.; Soares, Luciana A.; Silva, Julhiany F.; Oliveira, Haroldo C.; Furlan, Maysa; Silva, Dulce H. S.; Bolzani, Vanderlan S.; Mendes-Giannini, Maria José S.; Fusco-Almeida, Ana Marisa

    2012-01-01

    Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae) are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa). It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC50. The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents. PMID:22675379

  13. Antifungal ellagitannin isolated from Euphorbia antisyphilitica Zucc

    PubMed Central

    Ascacio-Valdés, Juan; Burboa, Edgardo; Aguilera-Carbo, Antonio F; Aparicio, Mario; Pérez-Schmidt, Ramón; Rodríguez, Raúl; Aguilar, Cristóbal N

    2013-01-01

    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. PMID:23570015

  14. Current and Emerging Azole Antifungal Agents

    PubMed Central

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

    1999-01-01

    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. PMID:9880474

  15. Hydroxytyrosol expresses antifungal activity in vitro.

    PubMed

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

    2013-08-01

    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

  16. Antifungal Susceptibility Testing of Ascomycetous Yeasts Isolated from Animals.

    PubMed

    Álvarez-Pérez, Sergio; García, Marta E; Peláez, Teresa; Martínez-Nevado, Eva; Blanco, José L

    2016-08-01

    Recent studies suggest that antifungal resistance in yeast isolates of veterinary origin may be an underdiagnosed threat. We tested a collection of 92 ascomycetous yeast isolates that were obtained in Spain from birds, mammals and insects for antifungal susceptibility. MICs to amphotericin B and azoles were low, and no resistant isolates were detected. Despite these results, and given the potential role of animals as reservoirs of resistant strains, continuous monitoring of antifungal susceptibility in the veterinary setting is recommended. PMID:27216048

  17. [Synthesis and antifungal activity of butenafine hydrochloride (KP-363), a new benzylamine antifungal agent].

    PubMed

    Maeda, T; Takase, M; Ishibashi, A; Yamamoto, T; Sasaki, K; Arika, T; Yokoo, M; Amemiya, K

    1991-02-01

    In screening of new antifungal agents, bis(naphthalenemethyl)amines were found to have more potent antifungal activity than clotrimazole. Studies on their structure-activity relationships indicated that benzylamines had potent antifungal activity. Among them, butenafine hydrochloride (N-p-tert-butylbenzyl-N-methyl-1-naphthalenemethylamine hydrochloride, KP-363) has proved to show the strongest activity. It exhibits a wide spectrum activity in vitro against particularly dermatophytes (87 strains; minimal inhibitory concentration (MIC) range, 0.0015 to 0.05 microgram/ml), and also against Aspergillus (15 strains; MIC range, 0.025 to 0.78 microgram/ml), Cryptococcus neoformans (4 strains; MICs 0.78 and 1.56 micrograms/ml) and yeasts of genus Candida (67 strains; MIC range, 3.13 to greater than 100 micrograms/ml). PMID:2056447

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-06-01

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

  20. Antifungal Resistance and New Strategies to Control Fungal Infections

    PubMed Central

    Vandeputte, Patrick; Ferrari, Selene; Coste, Alix T.

    2012-01-01

    Despite improvement of antifungal therapies over the last 30 years, the phenomenon of antifungal resistance is still of major concern in clinical practice. In the last 10 years the molecular mechanisms underlying this phenomenon were extensively unraveled. In this paper, after a brief overview of currently available antifungals, molecular mechanisms of antifungal resistance will be detailed. It appears that major mechanisms of resistance are essential due to the deregulation of antifungal resistance effector genes. This deregulation is a consequence of point mutations occurring in transcriptional regulators of these effector genes. Resistance can also follow the emergence of point mutations directly in the genes coding antifungal targets. In addition we further describe new strategies currently undertaken to discover alternative therapy targets and antifungals. Identification of new antifungals is essentially achieved by the screening of natural or synthetic chemical compound collections. Discovery of new putative antifungal targets is performed through genome-wide approaches for a better understanding of the human pathogenic fungi biology. PMID:22187560

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

    PubMed Central

    Huh, Chang Ki; Hwang, Tae Yean

    2016-01-01

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

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

    PubMed

    Huh, Chang Ki; Hwang, Tae Yean

    2016-03-01

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

  3. EFFECT OF CONAZOLE FUNGICIDES ON REPRODUCTIVE DEVELOPMENT IN THE FEMALE RAT

    EPA Science Inventory

    Three triazole fungicides were evaluated for effects on female rat reproductive development. Rats were exposed via feed to propiconazole (P) (100, 500, or 2500 ppm), myclobutanil (M) (100, 500, or 2000 ppm), or triadimefon (T) (100, 500, or 1800 ppm) from gestation day 6 to postn...

  4. 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...

  5. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2011-01-01

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

  7. Antifungal and antiviral products of marine organisms.

    PubMed

    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

    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 β-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

  8. Chemical modification of antifungal polyene macrolide antibiotics

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

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

  9. Histone deacetylases: Targets for antifungal drug development

    PubMed Central

    Kmetzsch, Livia

    2015-01-01

    The interaction of pathogens and its hosts causes a drastic change in the transcriptional landscape in both cells. Among the several mechanisms of gene regulation, transcriptional initiation is probably the main point. In such scenario, the access of transcriptional machinery to promoter is highly regulated by post-translational modification of histones, such as acetylation, phosphorylation and others. Inhibition of histone deacetylases is able to reduce fungal pathogens fitness during infection and, therefore, is currently being considered for the development of new antifungal therapy strategies. PMID:26151486

  10. Combination Antifungal Therapy for Invasive Aspergillosis Revisited

    PubMed Central

    Panackal, Anil A.

    2016-01-01

    Invasive aspergillosis (IA) causes significant morbidity and mortality among immunocompromised hosts. Combination therapy with mold-active triazoles and echinocandins has been used with the hope of improving outcomes over monotherapy, especially in the setting of refractory disease. Herein, I update our prior systematic review and meta-analysis on combination therapy for salvage IA in the context of the recently published randomized clinical trial of combination therapy for primary IA. Clinicians should consider combination antifungals for IA in refractory disease despite immune reconstitution when there are concerns for resistance or pharmacokinetic variability. PMID:27441304

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

    PubMed Central

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

    2011-01-01

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

  12. Emerging Threats in Antifungal-Resistant Fungal Pathogens

    PubMed Central

    Sanglard, Dominique

    2016-01-01

    The use of antifungal drugs in the therapy of fungal diseases can lead to the development of antifungal resistance. Resistance has been described for virtually all antifungal agents in diverse pathogens, including Candida and Aspergillus species. The majority of resistance mechanisms have also been elucidated at the molecular level in these pathogens. Drug resistance genes and genome mutations have been identified. Therapeutic choices are limited for the control of fungal diseases, and it is tempting to combine several drugs to achieve better therapeutic efficacy. In the recent years, several novel resistance patterns have been observed, including antifungal resistance originating from environmental sources in Aspergillus fumigatus and the emergence of simultaneous resistance to different antifungal classes (multidrug resistance) in different Candida species. This review will summarize these current trends. PMID:27014694

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

    PubMed

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

    2016-08-15

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

  14. Synergistic Antifungal Effect of Glabridin and Fluconazole

    PubMed Central

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

    2014-01-01

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

  15. Microbial Biotransformation to Obtain New Antifungals

    PubMed Central

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

    2015-01-01

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

  16. Mechanisms of echinocandin antifungal drug resistance

    PubMed Central

    Perlin, David S.

    2015-01-01

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

  17. Novel antifungal peptides from Ceylon spinach seeds.

    PubMed

    Wang, H; Ng, T B

    2001-11-01

    Two novel antifungal peptides, designated alpha- and beta-basrubrins, respectively, were isolated from seeds of the Ceylon spinach Basella rubra. The purification procedure involved saline extraction, (NH(4))(2)SO(4) precipitation, ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose and FPLC-gel filtration on Superdex peptide column. alpha- and beta-basrubrins exhibited a molecular weight of 4.3 and 5 kDa, respectively. They inhibited translation in a rabbit reticulocyte system with an IC(50) value of 400 and 100 nM, respectively. alpha- and beta-basrubrin inhibited HIV-1 reverse transcriptase by (79.4 +/- 7.8)% and (54.6 +/- 3.6)%, respectively, at a concentration of 400 microM, and (10.56 +/- 0.92)% and (2.12 +/- 0.81)%, respectively, at a concentration of 40 microM. Both alpha- and beta-basrubrins exerted potent antifungal activity toward Botrytis cinerea, Mycosphaerella arachidicola, and Fusarium oxysporum. PMID:11688973

  18. Antifungal Th Immunity: Growing up in Family

    PubMed Central

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

    2014-01-01

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

  19. Potentiation of Azole Antifungals by 2-Adamantanamine

    PubMed Central

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

    2013-01-01

    Azoles are among the most successful classes of antifungals. They act by inhibiting α-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

  20. Resistance to antifungals that target CYP51.

    PubMed

    Parker, Josie E; Warrilow, Andrew G S; Price, Claire L; Mullins, Jonathan G L; Kelly, Diane E; Kelly, Steven L

    2014-10-01

    Fungal diseases are an increasing global burden. Fungi are now recognised to kill more people annually than malaria, whilst in agriculture, fungi threaten crop yields and food security. Azole resistance, mediated by several mechanisms including point mutations in the target enzyme (CYP51), is increasing through selection pressure as a result of widespread use of triazole fungicides in agriculture and triazole antifungal drugs in the clinic. Mutations similar to those seen in clinical isolates as long ago as the 1990s in Candida albicans and later in Aspergillus fumigatus have been identified in agriculturally important fungal species and also wider combinations of point mutations. Recently, evidence that mutations originate in the field and now appear in clinical infections has been suggested. This situation is likely to increase in prevalence as triazole fungicide use continues to rise. Here, we review the progress made in understanding azole resistance found amongst clinically and agriculturally important fungal species focussing on resistance mechanisms associated with CYP51. Biochemical characterisation of wild-type and mutant CYP51 enzymes through ligand binding studies and azole IC50 determinations is an important tool for understanding azole susceptibility and can be used in conjunction with microbiological methods (MIC50 values), molecular biological studies (site-directed mutagenesis) and protein modelling studies to inform future antifungal development with increased specificity for the target enzyme over the host homologue. PMID:25320648

  1. [An update on antifungal susceptibility testing].

    PubMed

    Tapia P, Cecilia V

    2009-04-01

    Due to increasing of invasive fungal infections and emergeney of antifungal drugs resistant fungi, standardized methods of antifungal susceptibility testing (AST) have been developed. The Clinical Laboratory Standards Instutute (CLSI) and the European for Committee Antimicrobial Susceptibility Testing (EUCAST) have guidelines for susceptibility of yeasts by broth microdilution (M27-A2 and E. Dis. 7.1 documents, respectively). Both are equivalent, although they present methodological and interpretative breakpoints differences. In addition, the CLSI have the M38-A (for filamentous fungi) and M44-A (disk diffusion) documents, whereas EUCAST is developing a document for Aspergillus spp. Furthermore, commercial methods are available that display good correlation with the methods of reference such as E-test, Sensititre and Vitek2. The interpretation of the results must be careful because the determination of the minimum inhibitory concentration (CIM) is difficult for fungi, there are host factors involved and not always there is a correlation between MIC and clinical outcome. Due to these methods are laborious and require trained personnel, to ask for AST to a reference laboratory is recommendable. PMID:19621145

  2. Antifungal Quinoline Alkaloids from Waltheria indica.

    PubMed

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

    2016-02-26

    Chemical investigation of a dichloromethane extract of the aerial parts of Waltheria indica led to the isolation and characterization of five polyhydroxymethoxyflavonoids, namely, oxyanin A (1), vitexicarpin (3), chrysosplenol E (4), flindulatin (5), 5-hydroxy-3,7,4'-trimethoxyflavone (6), and six quinolone alkaloids, waltheriones M-Q (2, 7, 8, 10, 11) and 5(R)-vanessine (9). Among these, compounds 2, 7, 8, 10, and 11 have not yet been described in the literature. Their chemical structures were established by means of spectroscopic data interpretation including (1)H and (13)C, HSQC, HMBC, COSY, and NOESY NMR experiments and UV, IR, and HRESIMS. The absolute configurations of the compounds were established by ECD. The isolated constituents and 10 additional quinoline alkaloids previously isolated from the roots of the plant were evaluated for their in vitro antifungal activity against the human fungal pathogen Candida albicans, and 10 compounds (7, 9, 11-16, 18, 21) showed growth inhibitory activity on both planktonic cells and biofilms (MIC ≤ 32 μg/mL). Their spectrum of activity against other pathogenic Candida species and their cytotoxicity against human HeLa cells were also determined. In addition, the cytological effect of the antifungal isolated compounds on the ultrastructure of C. albicans was evaluated by transmission electron microscopy. PMID:26848627

  3. Antifungal drug resistance of oral fungi.

    PubMed

    Niimi, Masakazu; Firth, Norman A; Cannon, Richard D

    2010-02-01

    Fungi comprise a minor component of the oral microbiota but give rise to oral disease in a significant proportion of the population. The most common form of oral fungal disease is oral candidiasis, which has a number of presentations. The mainstay for the treatment of oral candidiasis is the use of polyenes, such as nystatin and amphotericin B, and azoles including miconazole, fluconazole, and itraconazole. Resistance of fungi to polyenes is rare, but some Candida species, such as Candida glabrata and C. krusei, are innately less susceptible to azoles, and C. albicans can acquire azole resistance. The main mechanism of high-level fungal azole resistance, measured in vitro, is energy-dependent drug efflux. Most fungi in the oral cavity, however, are present in multispecies biofilms that typically demonstrate an antifungal resistance phenotype. This resistance is the result of multiple factors including the expression of efflux pumps in the fungal cell membrane, biofilm matrix permeability, and a stress response in the fungal cell. Removal of dental biofilms, or treatments to prevent biofilm development in combination with antifungal drugs, may enable better treatment and prevention of oral fungal disease. PMID:20155503

  4. Microbial Biotransformation to Obtain New Antifungals.

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2012-08-01

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

  6. Pharmacokinetics and Pharmacodynamics of Antifungals in Children: Clinical Implications

    PubMed Central

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

    2014-01-01

    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 like fluconazole, voriconazole, and micafungin require higher dosing than in adults due to faster clearance in children. As a result, dosing recommendations are specific to bracketed ranges of age. Pharmacodynamics principles of antifungals mostly rely on in vitro and in vivo models but very few pharmacodynamics studies specifically address IFD in children. 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

  7. Antifungal Treatment in Stem Cell Transplantation Centers in Turkey

    PubMed Central

    Akan, Hamdi; Atilla, Erden

    2016-01-01

    Despite the development of various guidelines, the approach to antifungal treatment in stem cell transplantation centers differs according to country or even between centers. This led to the development of another survey that aims to understand the antifungal treatment policies of Turkish stem cell transplantation centers. Although there has been an increasing trend towards the use of diagnostic-based treatments in Turkey in the last few years, empirical treatment is still the main approach. The practices of the stem cell transplantation centers reflect the general trends and controversies in this area, while there is a considerable use of antifungal combination therapy. PMID:25913124

  8. Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies.

    PubMed

    Simic, Milena; Paunovic, Nikola; Boric, Ivan; Randjelovic, Jelena; Vojnovic, Sandra; Nikodinovic-Runic, Jasmina; Pekmezovic, Marina; Savic, Vladimir

    2016-01-01

    A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds. PMID:26586600

  9. Neutral red assay in minimum fungicidal concentrations of antifungal agents.

    PubMed

    Fukuda, T; Naka, W; Tajima, S; Nishikawa, T

    1996-01-01

    We assayed the fungicidal effects of antifungal agents using neutral red staining. Fungal elements of Trichophyton mentagrophytes and T. rubrum were treated with various concentrations of antifungal agents in 96-well filtration plates and then stained with neutral red. The amount of neutral red incorporated by the surviving viable cells was determined from the automated spectrophotometric readings at 550 nm. The minimum fungicidal concentrations (MFCs) of antifungal agents determined by this assay correlated well with those determined by conventional assay. This newly developed procedure should provide a rapid, reproducible, quantitative, qualitative and semi-automated susceptibility test for determination of the MFCs of the fungicidal agents. PMID:8912170

  10. Novel drug delivery strategies for improving econazole antifungal action.

    PubMed

    Firooz, Alireza; Nafisi, Shohreh; Maibach, Howard I

    2015-11-10

    Econazole is a commonly used azole antifungal in clinical treatment of superficial fungal infections. It is generally used as conventional cream and gel preparations under the brand names of Spectazole (United States), Ecostatin (Canada), Pevaryl (Western Europe). Treatment efficiency of antifungal drugs depends on their penetration through target layers of skin at effective concentrations. Econazole's poor water solubility limits its bioavailability and antifungal effects. Therefore, formulation strategies have been examined for delivering econazole through targeted skin sites. The present overview focuses on novel nano-based formulation approaches used to improve econazole penetration through skin for treatment of superficial fungal infections. PMID:26383840

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

    PubMed

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

    2015-10-01

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

  12. Antifungal Susceptibilities of Bloodstream Isolates of Candida Species from Nine Hospitals in Korea: Application of New Antifungal Breakpoints and Relationship to Antifungal Usage

    PubMed Central

    Won, Eun Jeong; Shin, Jong Hee; Choi, Min Ji; Lee, Wee Gyo; Park, Yeon-Joon; Uh, Young; Kim, Shine-Young; Lee, Mi-Kyung; Kim, Soo Hyun; Shin, Myung Geun; Suh, Soon Pal; Ryang, Dong Wook

    2015-01-01

    We applied the new clinical breakpoints (CBPs) of the Clinical and Laboratory Standards Institute (CLSI) to a multicenter study to determine the antifungal susceptibility of bloodstream infection (BSI) isolates of Candida species in Korea, and determined the relationship between the frequency of antifungal-resistant Candida BSI isolates and antifungal use at hospitals. Four hundred and fifty BSI isolates of Candida species were collected over a 1-year period in 2011 from nine hospitals. The susceptibilities of the isolates to four antifungal agents were determined using the CLSI M27 broth microdilution method. By applying the species-specific CBPs, non-susceptibility to fluconazole was found in 16.4% (70/428) of isolates, comprising 2.6% resistant and 13.8% susceptible-dose dependent isolates. However, non-susceptibility to voriconazole, caspofungin, or micafungin was found in 0% (0/370), 0% (0/437), or 0.5% (2/437) of the Candida BSI isolates, respectively. Of the 450 isolates, 72 (16.0%) showed decreased susceptibility to fluconazole [minimum inhibitory concentration (MIC) ≥4 μg/ml]. The total usage of systemic antifungals varied considerably among the hospitals, ranging from 190.0 to 7.7 defined daily dose per 1,000 patient days, and fluconazole was the most commonly prescribed agent (46.3%). By Spearman’s correlation analysis, fluconazole usage did not show a significant correlation with the percentage of fluconazole resistant isolates at hospitals. However, fluconazole usage was significantly correlated with the percentage of fluconazole non-susceptible isolates (r = 0.733; P = 0.025) or the percentage of isolates with decreased susceptibility to fluconazole (MIC ≥4 μg/ml) (r = 0.700; P = 0.036) at hospitals. Our work represents the first South Korean multicenter study demonstrating an association between antifungal use and antifungal resistance among BSI isolates of Candida at hospitals using the new CBPs of the CLSI. PMID:25706866

  13. Voriconazole: a new triazole antifungal agent.

    PubMed

    Johnson, Leonard B; Kauffman, Carol A

    2003-03-01

    Voriconazole is a second-generation azole antifungal agent that shows excellent in vitro activity against a wide variety of yeasts and molds. It can be given by either the intravenous or the oral route; the oral formulation has excellent bioavailability. The side effect profile of voriconazole is unique in that non-sight-threatening, transient visual disturbances occur in approximately 30% of patients given the drug. Rash (which can manifest as photosensitivity) and hepatitis also occur. The potential for drug-drug interactions is high and requires that careful attention be given to dosage regimens and monitoring of serum levels and effects of interacting drugs. Voriconazole has been approved for the treatment of invasive aspergillosis and refractory infections with Pseudallescheria/Scedosporium and Fusarium species, and it will likely become the drug of choice for treatment of serious infections with those filamentous fungi. PMID:12594645

  14. Overview of medically important antifungal azole derivatives.

    PubMed Central

    Fromtling, R A

    1988-01-01

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

  15. Probiotics as Antifungals in Mucosal Candidiasis.

    PubMed

    Matsubara, Victor H; Bandara, H M H N; Mayer, Marcia P A; Samaranayake, Lakshman P

    2016-05-01

    Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections. PMID:26826375

  16. Antifungal steroid saponins from Dioscorea cayenensis.

    PubMed

    Sautour, M; Mitaine-Offer, A-C; Miyamoto, T; Dongmo, A; Lacaille-Dubois, M-A

    2004-01-01

    From the rhizomes of Dioscorea cayenensis Lam.-Holl (Dioscoreaceae), the new 26- O- beta- D-glucopyranosyl-22-methoxy-3 beta,26-dihydroxy-25( R)-furost-5-en-3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 1) was isolated together with the known dioscin ( 2) and diosgenin 3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 3). Their structures were established on the basis of spectral data. Compound 2 exhibited antifungal activity against the human pathogenic yeasts Candida albicans, C. glabrata and C. tropicalis (MICs of 12.5, 12.5 and 25 micro g/mL, respectively) whereas 3 showed weak activity and 1 was inactive. PMID:14765305

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

    PubMed

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

    2002-08-01

    The methanol extract of the fruit pulp of Bromelia pinguin was evaluated for its antifungal activity. The extract showed a significant activity against some Trichophyton strains, although Candida strains were generally insensitive. PMID:12165338

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

    SciTech Connect

    Schreck, Carl

    1991-09-01

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

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

    SciTech Connect

    Schreck, Carl

    1993-10-01

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

  20. Antioxidant and antifungal activity of Verbena officinalis L. leaves.

    PubMed

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

    2008-09-01

    The scavenging activity against DPPH (1,1-diphenil-2-picrylhydrazyl) radical and the antifungal effect against chloroform, 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 also investigated. The results suggest that 50% methanolic extract and caffeoyl derivatives could potentially be considered as excellent and readily available sources of natural antifungal and antioxidant compounds. PMID:18498054

  1. Antifungal activity of polymer-based copper nanocomposite coatings

    NASA Astrophysics Data System (ADS)

    Cioffi, Nicola; Torsi, Luisa; Ditaranto, Nicoletta; Sabbatini, Luigia; Zambonin, Pier Giorgio; Tantillo, Giuseppina; Ghibelli, Lina; D'Alessio, Maria; Bleve-Zacheo, Teresa; Traversa, Enrico

    2004-09-01

    Eukaryotes, such as fungi, can be harmful pathogen agents, and the control of their bioactivity is critical as humans are eukaryote organisms, too. Here, copper/polymer nanocomposites are proposed as antifungal spinnable coatings with controlled copper-releasing properties. The tests of the bioactivity show that fungal growth is inhibited on the nanocomposite-coated plates, and the antifungal activity can be modulated by controlling the Cu nanoparticle loading.

  2. Antibacterial and antifungal activity of Indonesian ethnomedical plants.

    PubMed

    Goun, E; Cunningham, G; Chu, D; Nguyen, C; Miles, D

    2003-09-01

    Methylene chloride and methanol extracts of 20 Indonesian plants with ethnomedical uses have been assessed for in vitro antibacterial and antifungal properties by disk diffusion method. Extracts of the six plants: Terminalia catappa, Swietenia mahagoni Jacq., Phyllanthus acuminatus, Ipomoea spp., Tylophora asthmatica and Hyptis brevipes demonstrated high activity in this bioassay system. These findings should stimulate the search for novel, natural product such as new antibacterial and antifungal agents. PMID:12946723

  3. Chemosensitization as a Means to Augment Commercial Antifungal Agents

    PubMed Central

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

    2012-01-01

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

  4. Amphiphilic Tobramycin Analogues as Antibacterial and Antifungal Agents

    PubMed Central

    Shrestha, Sanjib K.; Fosso, Marina Y.; Green, Keith D.

    2015-01-01

    In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C12 and C14 chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter and 1.95 to 7.8 mg/liter, respectively. However, C4, C6, and C8 TOB analogues and TOB itself exhibited little to no antifungal activity. Fifty percent inhibitory concentrations (IC50s) for the most potent TOB analogues (C12 and C14) against A549 and Beas 2B cells were 4- to 64-fold and 32- to 64-fold higher, respectively, than their antifungal MIC values against various fungi. Unlike conventional aminoglycoside antibiotics, TOB analogues with alkyl chain lengths of C12 and C14 appear to inhibit fungi by inducing apoptosis and disrupting the fungal membrane as a novel mechanism of action. Amphiphilic TOB analogues showed broad-spectrum antifungal activities with minimal mammalian cell cytotoxicity. This study provides novel lead compounds for the development of antifungal drugs. PMID:26033722

  5. Update on antifungal drug resistance mechanisms of Aspergillus fumigatus.

    PubMed

    Chamilos, G; Kontoyiannis, D P

    2005-12-01

    Although the arsenal of agents with anti-Aspergillus activity has expanded over the last decade, mortality due to invasive aspergillosis (IA) remains unacceptably high. Aspergillus fumigatus still accounts for the majority of cases of IA; however less susceptible to antifungals non-fumigatus aspergilli began to emerge. Antifungal drug resistance of Aspergillus might partially account for treatment failures. Recent advances in our understanding of mechanisms of antifungal drug action in Aspergillus, along with the standardization of in vitro susceptibility testing methods, has brought resistance testing to the forefront of clinical mycology. In addition, molecular biology has started to shed light on the mechanisms of resistance of A. fumigatus to azoles and the echinocandins, while genome-based assays show promise for high-throughput screening for genotypic antifungal resistance. Several problems remain, however, in the study of this complex area. Large multicenter clinical studies--point prevalence or longitudinal--to capture the incidence and prevalence of antifungal resistance in A. fumigatus isolates are lacking. Correlation of in vitro susceptibility with clinical outcome and susceptibility breakpoints has not been established. In addition, the issue of cross-resistance between the newer triazoles is of concern. Furthermore, in vitro resistance testing for polyenes and echinocandins is difficult, and their mechanisms of resistance are largely unknown. This review examines challenges in the diagnosis, epidemiology, and mechanisms of antifungal drug resistance in A. fumigatus. PMID:16488654

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

    PubMed

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

    2012-04-01

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

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

    PubMed

    Nittayananta, W

    2016-04-01

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

  8. Role of antifungal agents in the treatment of seborrheic dermatitis.

    PubMed

    Gupta, Aditya K; Nicol, Karyn; Batra, Roma

    2004-01-01

    Seborrheic dermatitis is a superficial fungal disease of the skin, occurring in areas rich in sebaceous glands. It is thought that an association exists between Malassezia yeasts and seborrheic dermatitis. This may, in part, be due to an abnormal or inflammatory immune response to these yeasts. The azoles represent the largest class of antifungals used in the treatment of this disease to date. In addition to their antifungal properties, some azoles, including bifonazole, itraconazole, and ketoconazole, have demonstrated anti-inflammatory activity, which may be beneficial in alleviating symptoms. Other topical antifungal agents, such as the allylamines (terbinafine), benzylamines (butenafine), hydroxypyridones (ciclopirox), and immunomodulators (pimecrolimus and tacrolimus), have also been effective. In addition, recent studies have revealed that tea tree oil (Melaleuca oil), honey, and cinnamic acid have antifungal activity against Malassezia species, which may be of benefit in the treatment of seborrheic dermatitis. In cases where seborrheic dermatitis is widespread, the use of an oral therapy, such as ketoconazole, itraconazole, and terbinafine, may be preferred. Essentially, antifungal therapy reduces the number of yeasts on the skin, leading to an improvement in seborrheic dermatitis. With a wide availability of preparations, including creams, shampoos, and oral formulations, antifungal agents are safe and effective in the treatment of seborrheic dermatitis. PMID:15663338

  9. Pharmacokinetics of antifungal agents in onychomycoses.

    PubMed

    Debruyne, D; Coquerel, A

    2001-01-01

    Onychomycosis is caused by infection by fungi, mainly dermatophytes and nondermatophyte yeasts or moulds; it affects the fingernails and, more frequently, the toenails. Dermatophytes are responsible for about 90 to 95% of fungal infections. Trichophyton rubrum is the most common dermatophyte; Candida albicans is the major nondermatophyte yeast. Although topical therapy of onchomycosis does not lead to systemic adverse effects or interactions with concomitantly taken drugs, it does not provide high cure rates and requires complete compliance from the patient. At present there are 3 oral antifungal medications that are generally used for the short term treatment of onychomycosis: itraconazole, terbinafine and fluconazole. The persistence of these active drugs in nails allows weekly administration, reduced treatment or a pulse regimen. Good clinical and mycological efficacies are obtained with itraconazole 100 to 200 mg daily, terbinafine 250mg daily for 3 months, or fluconazole 150 mg weekly for at least 6 months. Itraconazole is a synthetic triazole with a broad spectrum of action. It is well absorbed when administered orally and can be detected in nails 1 to 2 weeks after the start of therapy. The nail : plasma ratio stabilises at around 1 by week 18 of treatment. Itraconazole is still detectable in nails 27 weeks after stopping administration. Nail concentrations are higher than the minimum inhibitory concentration (MIC) for most dermatophytes and Candida species from the first month of treatment. The elimination half-life of itraconazole from nails is long, ranging from 32 to 147 days. Terbinafine is a synthetic allylamine that is effective against dermatophytes. Terbinafine is well absorbed from the gastrointestinal tract, and the time to reach effective concentrations in nail is 1 to 2 weeks. The half-life is from 24 to 156 days, explaining the observed persistence of terbinafine in nails for longer than 252 days. Fluconazole is a bis-triazole broad spectrum

  10. Interaction of Common Azole Antifungals with P Glycoprotein

    PubMed Central

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

    2002-01-01

    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 interaction could both affect the disposition and exposure to azole antifungal therapeutics and partially explain the clinical drug interactions observed with some antifungals. Using a whole-cell assay in which the retention of a marker substrate is evaluated and quantified, we studied the abilities of the most widely prescribed orally administered azole antifungals to inhibit the function of this transporter. In a cell line presenting an overexpressed amount of the human P-gp transporter, itraconazole and ketoconazole inhibited P-gp function with 50% inhibitory concentrations (IC50s) of ∼2 and ∼6 μM, respectively. Cyclosporin A was inhibitory with an IC50 of 1.4 μM in this system. Uniquely, fluconazole had no effect in this assay, a result consistent with known clinical interactions. The effects of these azole antifungals on ATP consumption by P-gp (representing transport activity) were also assessed, and the Km values were congruent with the IC50s. Therefore, exposure of tissue to the azole antifungals may be modulated by human P-gp, and the clinical interactions of azole antifungals with other drugs may be due, in part, to inhibition of P-gp transport. PMID:11751127

  11. New generation azole antifungals in clinical investigation.

    PubMed

    Girmenia, Corrado

    2009-09-01

    Considerable progress in treating systemic mycoses has been achieved in the past years through development of new drugs in association with more advanced diagnostic procedures. Here, we review the pharmacological, microbiological and clinical development progress with the so-called 'second generation' triazoles: voriconazole, posaconazole, ravuconazole, isavuconazole and albaconazole. All these drugs exhibit a favourable pharmacokinetic and toxicity profile and possess high activity against resistant and emerging pathogens. However, only voriconazole and posaconazole have been adequately investigated in Phase III studies and have been approved by the regulatory agencies in the treatment and prophylaxis of invasive fungal infections, respectively. On the contrary, ravuconazole, isavuconazole and albaconazole have not been investigated in adequate clinical trials and, in the absence of proper data, the real possibilities of these agents as competitors for the treatment and prevention of invasive mycoses in the clinical setting are still unknown. The drug interactions and the variability in the absorption and/or metabolism of the triazoles, in particular voriconazole and posaconazole, may determine an unpredictable exposure of the pathogens to the antifungal treatments. Literature evidences strongly support the use of therapeutic drug monitoring for these triazoles which may be crucial for the proper management of severe invasive fungal infections. PMID:19678798

  12. Antifungal Hydrolases in Pea Tissue 1

    PubMed Central

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

    1988-01-01

    Chitinase and β-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 β-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 β-1,3-glucanase, did not inhibit fungal growth. Purified chitinase and β-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 β-1,3-glucanase alone. However, combinations of purified chitinase and β-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 β-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 PMID:16666407

  13. Antifungal activity of plant and bacterial ureases.

    PubMed

    Becker-Ritt, A B; Martinelli, A H S; Mitidieri, S; Feder, V; Wassermann, G E; Santi, L; Vainstein, M H; Oliveira, J T A; Fiuza, L M; Pasquali, G; Carlini, C R

    2007-12-01

    Ureases (EC 3.5.1.5) are nickel-dependent metalloenzymes that catalyze the hydrolysis of urea to ammonia and carbon dioxide. Produced by plants, fungi and bacteria, but not by animals, ureases share significant homology and similar mechanisms of catalysis, although differing in quaternary structures. While fungal and plant ureases are homo-oligomeric proteins of 90 kDa subunits, bacterial ureases are multimers of two (e.g. Helicobacter pylori) or three subunit complexes. It has been proposed that in plants these enzymes are involved in nitrogen bioavailability and in protection against pathogens. Previous studies by our group have shown that plant ureases, but not a bacterial (Bacillus pasteurii) urease, display insecticidal activity. Herein we demonstrate that (Glycine max) embryo-specific soybean urease, jackbean (Canavalia ensiformis) major urease and a recombinant H. pylori urease impair growth of selected phytopathogenic fungi at sub-micromolar concentrations. This antifungal property of ureases is not affected by treatment of the proteins with an irreversible inhibitor of the ureolytic activity. Scanning electron microscopy of urease-treated fungi suggests plasmolysis and cell wall injuries. Altogether, our data indicate that ureases probably contribute to the plant arsenal of defense compounds against predators and phytopathogens and that the urease defense mechanism is independent of ammonia release from urea. PMID:17825863

  14. Antifungal Indole Alkaloids from Winchia calophylla.

    PubMed

    Yang, Mei-Li; Chen, Jia; Sun, Meng; Zhang, Dong-Bo; Gao, Kun

    2016-05-01

    Ten indole alkaloids (1-10) were obtained from an antifungal extract of Winchia calophylla, of which two (2 and 4) were new. N(4)-Methyl-10-hydroxyl-desacetylakuammilin (2) was an akuammiline-type indole alkaloid. N(1)-Methyl-echitaminic acid (4) was an unusual zwitterion with a basic vincorine-type skeleton. This is the first report of 10 in W. calophylla. The structures of all of the compounds were determined based on spectroscopic data, and their bioactivities were assessed. Compound 1 showed potent activity against the plant pathogenic fungi of Penicillium italicum and Fusarium oxysporum f.sp cubens with IC50 s of 10.4 and 11.5 µM, respectively, and 3 inhibited Rhizoctonia solani with an IC50 of 11.7 µM. Compounds 2 and 4 showed weak cytotoxicity against the human leukemic cell line HL-60 in vitro with IC50 s of 51.4 and 75.3 µM, respectively. Compounds 1 and 2 displayed weak activity against acetylcholinesterase with IC50 s around 61.3 and 52.6 µM, respectively. PMID:27002397

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2016-09-01

    Candida spp. are the most common opportunistic mycosis worldwide. Although Candida albicans is the most common cause of urinary tract infections, the frequency of non-albicans Candida species is increasing with common use of antifungal in the prophylaxis and treatment. This may lead to difficulties in treatment. Antifungal tests should be applied with identification of species for effective treatment. In this study, identification of Candida species isolated from urine culture and investigation of susceptibility of these strains to amphotericin B, flucytosine, fluconazole, voriconazole was aimed. In this study, 58 Candida strains isolated from urine cultures at Osmaniye State Hospital between January 2012 and April 2013 were included. Urine culture and antifungal susceptibility tests were applied. Incidence rate of Candida spp. was determined as C. albicans (56.9%), Candida glabrata (20.6%), Candida tropicalis (10.3%), Candida parapsilosis (7%), Candida krusei (3.4%), Candida kefyr (1.8%). Most of the isolates were susceptible to amphotericin B, flucytosine, fluconazole, voriconazole. Twenty three (39.7%) Candida strains were isolated from internal medical branches and Intensive Care Unit and 12 (20.6%) from the Surgical Medical Branches. C. albicans and C. glabrata species were isolated most frequently as a candiduria factor in this hospital between January 2012 and April 2013. The analysis of antifungal susceptibility profile shows no significant resistance to antifungals. PMID:27452427

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

    PubMed

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

    2013-01-01

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

  18. In Search of the Holy Grail of Antifungal Therapy

    PubMed Central

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

    2008-01-01

    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. PMID:18596853

  19. Antifungal activity of multifunctional Fe 3O 4-Ag nanocolloids

    NASA Astrophysics Data System (ADS)

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

    2011-05-01

    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 μg/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.

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

    PubMed

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

    2015-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. Antifungal Effect of Chitosan as Ca2+ Channel Blocker

    PubMed Central

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

    2016-01-01

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

  3. Survey of small antifungal peptides with chemotherapeutic potential.

    PubMed

    Desbois, Andrew P; Tschörner, David; Coote, Peter J

    2011-08-01

    Many cationic peptides with antimicrobial properties have been isolated from bacteria, fungi, plants, and animals. These peptides vary in molecular size, potency and spectra of activities. This report surveyed the literature to highlight the peptides that have antifungal activity and greatest potential for development as new therapeutic agents. Thus, to be included in the evaluation, each peptide had to fulfil the following criteria: (i) potent antifungal activity, (ii) no, or minimal, mammalian cell toxicity, (iii) of ≤25 amino acids in length, which minimises the costs of synthesis, reduces immunogenicity and enhances bioavailability and stability in vivo, (iv) minimal post-translational modifications (also reduces the production costs). The ~80 peptides that satisfied these criteria are discussed with respect to their structures, mechanisms of antimicrobial action and in vitro and in vivo toxicities. Certainly, some of these small peptides warrant further study and have potential for future exploitation as new antifungal agents. PMID:21470150

  4. Antifungal Effect of Chitosan as Ca(2+) Channel Blocker.

    PubMed

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

    2016-06-01

    The aim of this study was to investigate antifungal activity of a range of different molecular weight (MW) chitosan against Penicillium italicum. Our results demonstrate that the antifungal activity was dependent both the MW and concentration of the chitosan. Among a series of chitosan derived from the hydrolysis of high MW chitosan, the fractions containing various sizes of chitosan ranging from 3 to 15 glucosamine units named as chitooligomers-F2 (CO-F2) was found to show the highest antifungal activity against P. italicum. Furthermore, the effect of CO-F2 toward this fungus was significantly reduced in the presence of Ca(2+), whereas its effect was recovered by ethylenediaminetetraacetic acid, suggesting that the CO-F2 acts via disruption of Ca(2+) gradient required for survival of the fungus. Our results suggest that CO-F2 may serve as potential compounds to develop alternatives to synthetic fungicides for the control of the postharvest diseases. PMID:27298599

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

    PubMed

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

    2013-03-01

    Citrus essential oils (EOs) are volatile compounds from citrus peels and widely used in perfumes, cosmetics, soaps and aromatherapy. In this study, inhibition of citrus EOs extracted from Vietnamese orange (Citrus sinensis), mandarin (Citrus reticulata Blanco), pomelo (Citrus grandis Osbeck) and lime (Citrus aurantifolia Swingle) on the growth of plant pathogenic fungi, Mucor hiemalis, Penicillium expansum and Fusarium proliferatum was investigated. The EOs of the citrus peels were obtained by cold-pressing method and the antifungal activity of EOs was evaluated using the agar dilution method. The results show that the EOs had significant antifungal activity. Lime EO was the best inhibitor of M. hiemalis and F. proliferatum while pomelo EO was the most effective against P. expansum. These results indicate that citrus EOs can be used as antifungal natural products in the food, pharmaceutical and cosmetic industries. PMID:22799453

  6. Peptide-based Antifungal Therapies against Emerging Infections

    PubMed Central

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

    2010-01-01

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

  7. Enhancement of Commercial Antifungal Agents by Kojic Acid

    PubMed Central

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

    2012-01-01

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

  8. Antifungal effect of TONS504-photodynamic therapy on Malassezia furfur.

    PubMed

    Takahashi, Hidetoshi; Nakajima, Susumu; Sakata, Isao; Iizuka, Hajime

    2014-10-01

    Numerous reports indicate therapeutic efficacy of photodynamic therapy (PDT) against skin tumors, acne and for skin rejuvenation. However, few reports exist regarding its efficacy for fungal skin diseases. In order to determine the antifungal effect, PDT was applied on Malassezia furfur. M. furfur was cultured in the presence of a novel cationic photosensitizer, TONS504, and was irradiated with a 670-nm diode laser. TONS504-PDT showed a significant antifungal effect against M. furfur. The effect was irradiation dose- and TONS504 concentration-dependent and the maximal effect was observed at 100 J/cm2 and 1 μg/mL, respectively. In conclusion, TONS504-PDT showed antifungal effect against M. furfur in vitro, and may be a new therapeutic modality for M. furfur-related skin disorders. PMID:25226792

  9. Potent In Vitro Antifungal Activities of Naturally Occurring Acetylenic Acids▿

    PubMed Central

    Li, Xing-Cong; Jacob, Melissa R.; Khan, Shabana I.; Ashfaq, M. Khalid; Babu, K. Suresh; Agarwal, Ameeta K.; ElSohly, Hala N.; Manly, Susan P.; Clark, Alice M.

    2008-01-01

    Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C16 to C20: 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides. Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes, and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus, with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 μM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 μmol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies. PMID:18458131

  10. Atmospheric pressure cold plasma as an antifungal therapy

    NASA Astrophysics Data System (ADS)

    Sun, Peng; Sun, Yi; Wu, Haiyan; Zhu, Weidong; Lopez, Jose L.; Liu, Wei; Zhang, Jue; Li, Ruoyu; Fang, Jing

    2011-01-01

    A microhollow cathode based, direct-current, atmospheric pressure, He/O2 (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.

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

    PubMed

    Rosen, Theodore; Stein Gold, Linda F

    2016-03-01

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

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

    PubMed

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

    2015-01-01

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

  13. Atmospheric pressure cold plasma as an antifungal therapy

    SciTech Connect

    Sun Peng; Wu Haiyan; Sun Yi; Liu Wei; Li Ruoyu; Zhu Weidong; Lopez, Jose L.; Zhang Jue; Fang Jing

    2011-01-10

    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.

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

    PubMed

    Abirami, C P; Venugopal, Pankajalakshmi V

    2005-01-01

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

  15. Fungal virulence genes as targets for antifungal chemotherapy.

    PubMed Central

    Perfect, J R

    1996-01-01

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

  16. Antifungal Activities of SCY-078 (MK-3118) and Standard Antifungal Agents against Clinical Non-Aspergillus Mold Isolates

    PubMed Central

    Lamoth, Frédéric

    2015-01-01

    The limited armamentarium of active and oral antifungal drugs against emerging non-Aspergillus molds is of particular concern. Current antifungal agents and the new orally available beta-1,3-d-glucan synthase inhibitor SCY-078 were tested in vitro against 135 clinical non-Aspergillus mold isolates. Akin to echinocandins, SCY-078 showed no or poor activity against Mucoromycotina and Fusarium spp. However, SCY-078 was highly active against Paecilomyces variotii and was the only compound displaying some activity against notoriously panresistant Scedosporium prolificans. PMID:25896696

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2007-11-01

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

  19. Enhancement of commercial antifungal agents by kojic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Kojic acid (KA), a natural by-product of fungal fermentation, is a commonly used food and cosmetic additive. We show that KA increases activity of amphotericin B and strobilurin, medical and agricultural antifungal agents, respectively, possibly targeting the fungal antioxidative system. KA shows pr...

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

    PubMed

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

    2016-09-01

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

  1. Successful management of renal mucormycosis with antifungal therapy and drainage

    PubMed Central

    Devana, Sudheer K.; Bora, Girdhar S.; Mavuduru, Ravimohan S.; Panwar, Pankaj; Kakkar, Nandita; Mandal, Arup K.

    2016-01-01

    We report a case of isolated extensive renal mucormycosis in an immunocompetent adult, who was successfully managed conservatively without surgical debridement. To the best of our knowledge, this is the first case where antifungal therapy alone was sufficient even with such an extensive involvement. PMID:27127360

  2. Antifungal activity of heartwood extracts from three Juniperus species

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2015-01-01

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

  4. Chemosensitization as a means to augment commercial antifungal agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. Prediction of antifungal activity of gemini imidazolium compounds.

    PubMed

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

    2015-01-01

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

  6. In vitro antifungal activity of Schizozygia coffaeoides bail. (Apocynaceae) extracts.

    PubMed

    Kariba, R M; Siboe, G M; Dossaji, S F

    2001-01-01

    Leaf extracts of Schizozygia coffaeoides were investigated for antifungal activity using the disc diffusion assay technique. Petroleum ether 40-60 degrees C, dichloromethane-ethyl acetate (1:1) and methanol extracts were fungitoxic to Trichophyton mentagrophytes, Microsporum gypseum, Cladosporium cucumerinum and Candida albicans. The extracts were fungistatic in action. PMID:11137346

  7. Prediction of Antifungal Activity of Gemini Imidazolium Compounds

    PubMed Central

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

    2015-01-01

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

  8. Antibacterial and antifungal activity of liriodenine and related oxoaporphine alkaloids.

    PubMed

    Hufford, C D; Sharma, A S; Oguntimein, B O

    1980-10-01

    Liriodenine was evaluated for its antibacterial and antifungal activity against several microorganisms. Other related oxoaporphine alkaloids also were evaluated. Attempts to prepare oxoaporphine alkaloids from N-acetylnoraporphines were unsuccessful, but an unexpected phenanthrene alkaloid was obtained. A novel N-demethylation reaction was noted when oxogaucine methiodide and liriodenine methiodide were treated with alumina. PMID:7420287

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

    SciTech Connect

    Schreck, Carl

    1993-03-01

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

  10. [Antifungal activity of 5-benzilidene pyrrolone and furanone derivatives].

    PubMed

    de Carvalho, M G; Pitta, I da R; Galdino, S L; Takaki, G de C; Bergé, G

    1989-01-01

    The antifungal activity against Neurospora crassa of some 5-benzilidene pyrrolone and furanone derivatives was realised. Relations between the structure and this biological activity are established with Fujita-Ban and Hansch methods. The preponderant part of lipophilicity, resonance effect and E or Z configurations have been showed. PMID:2535109

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

    PubMed

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

    2016-07-19

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

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

    PubMed

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

    2016-03-01

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

  13. Antifungal Lock Therapy with Liposomal Amphotericin B: A Prospective Trial.

    PubMed

    McGhee, William; Michaels, Marian G; Martin, Judith M; Mazariegos, George V; Green, Michael

    2016-03-01

    We conducted a prospective pilot study to evaluate the potential role of combined systemic antifungal and liposomal amphotericin B lock therapy in children with intestinal insufficiency with fungal catheter-related bloodstream infections whose central venous catheters had not been removed. Our results provide supportive evidence for the conduct of larger clinical trials to confirm the efficacy and safety of this approach. PMID:26908494

  14. Determination of antifungal, biochemical and physiological features of Trichoderma koningiopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Trichoderma koningiopsis is a species that has been recently identified and has not yet been published, but is in press. Due to the absence of reported data on this species, antifungal, biochemical and physiological features were analyzed for the Trichoderma koningiopsis strain isolated from root se...

  15. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  16. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  17. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  18. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  19. 21 CFR 333.210 - Antifungal active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  20. Human Pharmacogenomic Variations and Their Implications for Antifungal Efficacy

    PubMed Central

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

    2006-01-01

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

  1. Antifungal activities of nine traditional Mexican medicinal plants.

    PubMed

    Navarro García, V M; Gonzalez, A; Fuentes, M; Aviles, M; Rios, M Y; Zepeda, G; Rojas, M G

    2003-07-01

    Eighteen plant extracts from nine traditional Mexican medicinal plants were tested for antifungal activity against two dermatophyte fungal species (Trichophyton mentagrophytes and Trichophyton rubrum), one non-dermatophyte (Aspergillus niger), and one yeast (Candida albicans). The strongest effect was manifested by the hexane extracts from Eupatorium aschenbornianum and Sedum oxypetalum, as well as the methanol extracts from Lysiloma acapulcensis and Annona cherimolia. PMID:12787958

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

    PubMed

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

    2013-08-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-08-01

    Sporotrichosis is a global subcutaneous fungal infection caused by the Sporothrix schenckii complex. Sporotrichosis is an uncommon infection in Iran, and there have been no phenotypic, molecular typing or antifungal susceptibility studies of Sporothrix species. This study aimed to identify nine Iranian isolates of the S. schenckii complex to the species level using colony morphology, carbohydrate assimilation tests, and PCR-sequencing of the calmodulin gene. The antifungal susceptibilities of these Sporothrix isolates to five antifungal agents (amphotericin B (AMB), voriconazole (VRC), itraconazole (ITC), fluconazole (FLC), and terbinafine (TRB)) were also evaluated according to the M27-A3 and M38-A2 protocols of the Clinical and Laboratory Standards Institute for yeast and mycelial phases, respectively. Five of seven clinical isolates were identified as S. schenckii, and two clinical and two environmental isolates were identified as S. globosa. This is the first report of S. globosa in Iran. There was significant agreement (73%) between the results of the phenotypic and genotypic identification methods. TRB and ITC were the most effective antifungals against the Sporothrix isolates. The minimum inhibitory concentration (MIC) values of TRB for the yeast and mycelial phases of S. schenckii differed significantly. There was also a significant difference in the minimum fungicidal concentration (MFC) values of AMB and TRB for the two phases. Considering the low efficacy of VRC and FLC and the wide MIC ranges of AMB (1-16 μg/ml and 1-8 μg/ml for yeast and mycelial forms, respectively) observed in the present study, in vitro antifungal susceptibility testing should be performed to determine appropriate therapeutic regimens. PMID:26933207

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

    PubMed Central

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

    2012-01-01

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

  7. Antifungal effects of citronella oil against Aspergillus niger ATCC 16404.

    PubMed

    Li, Wen-Ru; Shi, Qing-Shan; Ouyang, You-Sheng; Chen, Yi-Ben; Duan, Shun-Shan

    2013-08-01

    Essential oils are aromatic oily liquids obtained from some aromatic plant materials. Certain essential oils such as citronella oil contain antifungal activity, but the antifungal effect is still unknown. In this study, we explored the antifungal effect of citronella oil with Aspergillus niger ATCC 16404. The antifungal activity of citronella oil on conidia of A. niger was determined by poisoned food technique, broth dilution method, and disc volatility method. Experimental results indicated that the citronella oil has strong antifungal activity: 0.125 (v/v) and 0.25 % (v/v) citronella oil inhibited the growth of 5 × 10⁵ spore/ml conidia separately for 7 and 28 days while 0.5 % (v/v) citronella oil could completely kill the conidia of 5 × 10⁵ spore/ml. Moreover, the fungicidal kinetic curves revealed that more than 90 % conidia (initial concentration is 5 × 10⁵ spore/ml) were killed in all the treatments with 0.125 to 2 % citronella oil after 24 h. Furthermore, with increase of citronella oil concentration and treatment time, the antifungal activity was increased correspondingly. The 0.5 % (v/v) concentration of citronella oil was a threshold to kill the conidia thoroughly. The surviving conidia treated with 0.5 to 2 % citronella oil decreased by an order of magnitude every day, and no fungus survived after 10 days. With light microscope, scanning electron microscope, and transmission electron microscope, we found that citronella oil could lead to irreversible alteration of the hyphae and conidia. Based on our observation, we hypothesized that the citronella oil destroyed the cell wall of the A. niger hyphae, passed through the cell membrane, penetrated into the cytoplasm, and acted on the main organelles. Subsequently, the hyphae was collapsed and squashed due to large cytoplasm loss, and the organelles were severely destroyed. Similarly, citronella oil could lead to the rupture of hard cell wall and then act on the sporoplasm to kill the

  8. Antifungal activity of biflavones from Taxus baccata and Ginkgo biloba.

    PubMed

    Krauze-Baranowska, Mirosława; Wiwart, Marian

    2003-01-01

    Bilobetin and 4'''-O-methylamentoflavone were isolated and identified in the needles of Taxus baccata, for the first time in this species. The antifungal activity of biflavones from T. baccata and Ginkgo biloba, namely amentoflavone, 7-O-methylamentoflavone, bilobetin, ginkgetin, sciadopitysin and 2,3-dihydrosciadopitysin towards the fungi Alternaria alternata, Fusarium culmorum, Cladosporium oxysporum was determined employing computer-aided image analysis couplet to a microscope. Bilobetin exhibited a significant antifungal activity with values of ED50 14, 11 and 17 microM respectively. This compound completely inhibited the growth of germinating tubes of Cladosporium oxysporum and Fusarium culmorum at a concentration 100 microM. Activity of ginkgetin and 7-O-methylamentoflavone towards Alternaria alternata was stronger than that of bilobetin. Moreover, slight structural changes in the cell wall of Alternaria alternata exposed to ginkgetin at concentration of 200 microM were observed. PMID:12622229

  9. Design, synthesis and antifungal activity of novel furancarboxamide derivatives.

    PubMed

    Wen, Fang; Jin, Hong; Tao, Ke; Hou, Taiping

    2016-09-14

    Twenty-seven novel furancarboxamide derivatives with a diphenyl ether moiety were synthesized and evaluated for their antifungal activity against Rhizoctonia solani, Botrytis cirerea, Valsa mali and Sphaceloma ampelimum. Antifungal bioassay results indicated that most compounds had good or excellent fungicidal activities for R. solani and S. ampelimum at 20 mg L(-1). Among synthesized compounds, compound 18e showed a greater inhibitory effect against S. ampelimum, with half maximal effective concentration (EC50) values of 0.020 mg L(-1). This strong activity rivals currently used commercial fungicides, such as Boscalid and Carbendazim, and has great potential as a lead compound for future development of novel fungicides. PMID:27191618

  10. Conventional and alternative antifungal therapies to oral candidiasis

    PubMed Central

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

    2010-01-01

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

  11. Synthesis, characterization, and antifungal activity of novel quaternary chitosan derivatives.

    PubMed

    Li, Rongchun; Guo, Zhanyong; Jiang, Pingan

    2010-09-01

    Three novel quaternary chitosan derivatives were successfully synthesized by reaction of chloracetyl chitosan (CACS) with pyridine (PACS), 4-(5-chloro-2-hydroxybenzylideneamino)-pyridine (CHPACS), and 4-(5-bromo-2-hydroxybenzylideneamino)-pyridine (BHPACS). The chemical structure of the prepared chitosan derivatives was confirmed by Fourier transform infrared (FT-IR) and (13)C nuclear magnetic resonance ((13)C NMR) and their antifungal activity against Cladosporium cucumerinum, Monilinia fructicola, Colletotrichum lagenarium, and Fusarium oxysporum was assessed. Comparing with the antifungal activity of chitosan, CACS, and PACS, CHPACS and BHPACS exhibited obviously better inhibitory effects, which should be related to the synergistic reaction of chitosan itself with the grafted 2-[4-(5-chloro-2-hydroxybenzylideneamino)-pyridyl]acetyl and 2-[4-(5-bromo-2-hydroxybenzylideneamino)-pyridyl]acetyl. PMID:20615498

  12. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani

    PubMed Central

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

    2013-01-01

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

  13. Virulence and Resistance to Antifungal Therapies of Scopulariopsis Species.

    PubMed

    Paredes, Katihuska; Capilla, Javier; Mayayo, Emilio; Guarro, Josep

    2016-04-01

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

  14. Rondonin an antifungal peptide from spider (Acanthoscurria rondoniae) haemolymph

    PubMed Central

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

    2012-01-01

    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. PMID:24371568

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

    PubMed

    Li, Yan; Liu, Song; Qin, Yukun; Xing, Ronge; Chen, Xiaolin; Li, Kecheng; Li, Pengcheng

    2016-01-01

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

  16. In Vitro Screening of 10 Edible Thai Plants for Potential Antifungal Properties

    PubMed Central

    Luplertlop, Natthanej

    2014-01-01

    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

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

    Liu, Song; Xing, Ronge; Chen, Xiaolin

    2016-01-01

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

  19. Persistence of histoplasma in adrenals 7 years after antifungal therapy

    PubMed Central

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

    2013-01-01

    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

  20. Restricticin, a novel glycine-containing antifungal agent.

    PubMed

    Schwartz, R E; Dufresne, C; Flor, J E; Kempf, A J; Wilson, K E; Lam, T; Onishi, J; Milligan, J; Fromtling, R A; Abruzzo, G K

    1991-05-01

    Restricticin (1) is a naturally-occurring antifungal agent which contains triene, pyran and glycine ester functionalities and is unrelated to any previously known family of natural products. This unstable compound, as well as its corresponding N,N-dimethyl derivative (2), have been produced and isolated from both solid and liquid fermentations of Penicillium restrictum. The desglycyl hydrolysis product, restrictinol (3), was produced via the hydrolysis of pure restricticin and as an artifact of the isolation of restricticin. PMID:2061189

  1. Antifungal methylphenone derivatives and 5-methylcoumarins from Mutisia friesiana.

    PubMed

    Viturro, Carmen I; de la Fuente, Juana R; Maier, Marta S

    2003-01-01

    In addition to the known mutisicoumarin A, the aerial parts of the shrub Mutisia friesiana afforded five new methylphenones, two new 5-methylcoumarins and a new related chromone. Their structures were elucidated by spectroscopic methods 13C NMR data for mutisicoumarin A are reported for the first time. Mutisiphenones A and B and mutisicoumarin A showed antifungal activity against the phytopathogenic fungus Cladosporium cucumerinum. PMID:12939040

  2. Antifungal and larvicidal cordiaquinones from the roots of Cordia curassavica.

    PubMed

    Ioset, J R; Marston, A; Gupta, M P; Hostettmann, K

    2000-03-01

    In addition to the known cordiaquinones A and B, two novel meroterpenoid naphthoquinones, named cordiaquinones J and K, have been isolated from the roots of Cordia curassavica. Their structures were elucidated by spectrometric methods including EI, D/CI mass spectrometry, 1H, 13C and 2D-NMR experiments. The four naphthoquinones demonstrated antifungal activities against Cladosporium cucumerinum, Candida albicans and toxic properties against larvae of the yellow fever-transmitting mosquito Aedes aegypti. PMID:10724189

  3. Antifungal Activity of Ellagic Acid In Vitro and In Vivo.

    PubMed

    Li, Zhi-Jian; Guo, Xin; Dawuti, Gulina; Aibai, Silafu

    2015-07-01

    Ellagic acid (EA) has been shown to have antioxidant, antibacterial, and anti-inflammatory activities. In Uighur traditional medicine, Euphorbia humifusa Willd is used to treat fungal diseases, and recent studies suggest that it is the EA content which is responsible for its therapeutic effect. However, the effects of EA on antifungal activity have not yet been reported. This study aimed to investigate the inhibitory effect of EA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the National Committee for Clinical Laboratory Standards (M38-A and M27-A2) standard method in vitro. EA had a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 18.75 and 58.33 µg/ml. EA was also active against two Candida strains, with MICs between 25.0 and 75.0 µg/ml. It was inactive against Candida glabrata. The susceptibility of six species of dermatophytes to EA was comparable with that of the commercial antifungal, fluconazole. The most sensitive filamentous species was Trichophyton rubrum (MIC = 18.75 µg/ml). Studies on the mechanism of action using an HPLC-based assay and an enzyme linked immunosorbent assay showed that EA inhibited ergosterol biosynthesis and reduced the activity of sterol 14α-demethylase P450 (CYP51) in the Trichophyton rubrum membrane, respectively. An in vivo test demonstrated that topical administration of EA (4.0 and 8.0 mg/cm(2) ) significantly enhanced the cure rate in a guinea-pig infection model of Trichophyton rubrum. The results suggest that EA has the potential to be developed as a natural antifungal agent. PMID:25919446

  4. New and emerging antifungal agents: impact on respiratory infections.

    PubMed

    Feldmesser, Marta

    2003-01-01

    Fungal pathogens are increasingly important causes of respiratory disease, yet the number of antifungal agents available for clinical use is limited. Use of amphotericin B deoxycholate is hampered by severe toxicity. Triazole agents currently available have significant drug interactions; fluconazole has a limited spectrum of activity and itraconazole was, until recently, available only in oral formulations with limited bioavailability. The development of resistance to all three agents is increasingly being recognized and some filamentous fungi are resistant to the action of all of these agents. In the past few years, new antifungal agents and new formulations of existing agents have become available.The use of liposomal amphotericin B preparations is associated with reduced, but still substantial, rates of nephrotoxicity and infusion-related reactions. An intravenous formulation of itraconazole has been introduced, and several new triazole agents have been developed, with the view of identifying agents that have enhanced potency, broader spectra of action and improved pharmacodynamic properties. One of these, voriconazole, has completed large-scale clinical trials. In addition, caspofungin, the first of a new class of agents, the echinocandins, which inhibit cell wall glucan synthesis, was approved for use in the US in 2001 as salvage therapy for invasive aspergillosis. It is hoped that the availability of these agents will have a significant impact on the morbidity and mortality of fungal respiratory infections. However, at the present time, our ability to assess their impact is limited by the problematic nature of conducting trials for antifungal therapy. PMID:14719990

  5. Antifungal defensins and their role in plant defense.

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

    Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16-32 μg/mL and 8-16 μg/mL, respectively. The compounds' action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents. PMID:26007181

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Rashid, Rehana; Mukhtar, Farah; Khan, Abida

    2014-01-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Cytotoxic, trypanocidal, and antifungal activities of Eugenia jambolana L.

    PubMed

    dos Santos, Karla K A; Matias, Edinardo F F; Tintino, Saulo R; Souza, Celestina E S; Braga, Maria F B M; Guedes, Gláucia M M; Rolón, Miriam; Vega, Celeste; de Arias, Antonieta Rojas; Costa, José G M; Menezes, Irwin A; Coutinho, Henrique D M

    2012-01-01

    Chagas' disease, caused by Trypanosoma cruzi, is considered a public health problem. Nowadays, chemotherapy is the only available treatment for this disease, and the drugs currently used, nifurtimox and benzonidazole, present high toxicity levels. Alternatives for replacing these drugs are natural extracts from Eugenia jambolana, a plant used in traditional medicine because of its antimicrobial and biological activities. An ethanol extract from E. jambolana was prepared. To research in vitro anti-epimastigote activity, T. cruzi CL-B5 clone was used. Epimastigotes were inoculated at a concentration of 1×10(5)/mL in 200 μL of tryptose-liver infusion. For the cytotoxicity assay J774 macrophages were used. To examine antifungal activity, Candida albicans, Candida tropicalis, and Candida krusei were used. This is the first record of trypanocide activity for E. jambolana. The effective concentration capable of killing 50% of the parasites was 56.42 μg/mL. The minimum inhibitory concentration was ≤1,024 μg/mL. Metronidazole showed a potentiation of its antifungal effect when combined with the ethanol extract of E. jambolana. Thus our results indicate that E. jambolana could be a source of plant-derived natural products with anti-epimastigote and antifungal modifying activity with moderate toxicity. PMID:21877946

  12. In vitro Antifungal Activity of Luliconazole against Trichophyton spp.

    PubMed

    Maeda, Jun; Nanjoh, Yasuko; Koga, Hiroyasu; Toga, Tetsuo; Makimura, Koichi; Tsuboi, Ryoji

    2016-01-01

    The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) of luliconazole against Trichophyton rubrum (14 strains) and Trichophyton mentagrophytes (14 strains), which are the most common cause of tinea, were compared with those of 6 topical antifungal drugs of lanoconazole, bifonazole, efinaconazole, liranaftate, naftifine and terbinafine. Luliconazole showed the most potent antifungal activity (MIC90 =0.00098 μg/ml and MFC90 =0.0078 μg/ml) among the compounds tested against the two species. Efinaconazole and bifonazole, the drug of azole-class, showed a large MFC/MIC ratio. On the other hand, these ratios of luliconazole and lanoconazole were as small as those of liranaftate, naftifine and terbinafine which are thought to possess fungicidal mechanism. These results suggest that luliconazole possesses fungicidal activity against both species of Trichophyton. In this study, we found that luliconazole had the most potent antifungal activity among the major topical antimycotics used in Japan and the US. Luliconazole would be the best-in-class drug for dermatophytosis in clinics. PMID:26936346

  13. New constitutive latex osmotin-like proteins lacking antifungal activity.

    PubMed

    Freitas, Cleverson D T; Silva, Maria Z R; Bruno-Moreno, Frederico; Monteiro-Moreira, Ana C O; Moreira, Renato A; Ramos, Márcio V

    2015-11-01

    Proteins that share similar primary sequences to the protein originally described in salt-stressed tobacco cells have been named osmotins. So far, only two osmotin-like proteins were purified and characterized of latex fluids. Osmotin from Carica papaya latex is an inducible protein lacking antifungal activity, whereas the Calotropis procera latex osmotin is a constitutive antifungal protein. To get additional insights into this subject, we investigated osmotins in latex fluids of five species. Two potential osmotin-like proteins in Cryptostegia grandiflora and Plumeria rubra latex were detected by immunological cross-reactivity with polyclonal antibodies produced against the C. procera latex osmotin (CpOsm) by ELISA, Dot Blot and Western Blot assays. Osmotin-like proteins were not detected in the latex of Thevetia peruviana, Himatanthus drasticus and healthy Carica papaya fruits. Later, the two new osmotin-like proteins were purified through immunoaffinity chromatography with anti-CpOsm immobilized antibodies. Worth noting the chromatographic efficiency allowed for the purification of the osmotin-like protein belonging to H. drasticus latex, which was not detectable by immunoassays. The identification of the purified proteins was confirmed after MS/MS analyses of their tryptic digests. It is concluded that the constitutive osmotin-like proteins reported here share structural similarities to CpOsm. However, unlike CpOsm, they did not exhibit antifungal activity against Fusarium solani and Colletotrichum gloeosporioides. These results suggest that osmotins of different latex sources may be involved in distinct physiological or defensive events. PMID:26231325

  14. Cytocompatible antifungal acrylic resin containing silver nanoparticles for dentures

    PubMed Central

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

    2012-01-01

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

  15. Antifungal activity of topical microemulsion containing a thiophene derivative

    PubMed Central

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

    2014-01-01

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

  16. In vitro antifungal activities of luliconazole, a new topical imidazole.

    PubMed

    Koga, Hiroyasu; Nanjoh, Yasuko; Makimura, Koichi; Tsuboi, Ryoji

    2009-01-01

    Luliconazole is a topical antifungal drug newly developed in Japan. The present study compares the in vitro antifungal activity of luliconazole against clinically important dermatomycotic fungi with that of other representative antifungal drugs. The reference drugs chosen were five classes of nine topical agents, i.e., allylamine (terbinafine), thiocarbamate (liranaftate), benzylamine (butenafine), morpholine (amorolfine), and azole (ketoconazole, clotrimazole, neticonazole, miconazole and bifonazole). The minimum inhibitory concentrations (MIC) of luliconazole and the reference drugs against Trichophyton spp. (T. rubrum, T. mentagrophytes and T. tonsurans) and Candida albicans were measured by the standardized broth microdilution method. Luliconazole demonstrated greater potency against Trichophyton spp. (MIC range:

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

    PubMed

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

    2014-06-01

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

  18. Antifungal defensins and their role in plant defense

    PubMed Central

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

    2014-01-01

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

  19. An overview of antifungal peptides derived from insect.

    PubMed

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

    2016-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-06-01

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

  5. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    SciTech Connect

    Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

    2009-01-15

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  6. Defining the frontiers between antifungal resistance, tolerance and the concept of persistence.

    PubMed

    Delarze, Eric; Sanglard, Dominique

    2015-11-01

    A restricted number of antifungal agents are available for the therapy of fungal diseases. With the introduction of epidemiological cut-off values for each agent in important fungal pathogens based on the distribution of minimal inhibitory concentration (MIC), the distinction between wild type and drug-resistant populations has been facilitated. Antifungal resistance has been described for all currently available antifungal agents in several pathogens and most of the associated resistance mechanisms have been deciphered at the molecular level. Clinical breakpoints for some agents have been proposed and can have predictive value for the success or failure of therapy. Tolerance to antifungals has been a much more ignored area. By definition, tolerance operates at antifungal concentrations above individual intrinsic inhibitory values. Important is that tolerance to antifungal agents favours the emergence of persister cells, which are able to survive antifungal therapy and can cause relapses. Here we will review the current knowledge on antifungal tolerance, its potential mechanisms and also evaluate the role of antifungal tolerance in the efficacy of drug treatments. PMID:26690338

  7. Monosubstituted Benzene Derivatives from Fruits of Ficus hirta and Their Antifungal Activity against Phytopathogen Penicillium italicum.

    PubMed

    Wan, Chunpeng; Han, Jianxin; Chen, Chuying; Yao, Liangliang; Chen, Jinyin; Yuan, Tao

    2016-07-20

    Ficus hirta, a widely consumed food by Hakka people, has been reported to show potent antifungal activity against phytopathogen Penicillium italicum. However, there is no report of chemical constituents responsible for the antifungal activity. In the current study, nine monosubstituted benzene derivatives, including three new derivatives (1-3), were isolated from the fruits of F. hirta. The structures of these isolates were elucidated on the basis of the analysis of spectroscopic data (mass spectrometry and nuclear magnetic resonance). All of the isolates were evaluated for antifungal activities against P. italicum. At an equivalent concentration, compound 1 exhibited stronger antifungal activity than that of the ethanol extract of F. hirta fruits. PMID:27381890

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    1991-01-01

    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

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

    PubMed

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

    2016-02-01

    This study was undertaken to assess the antifungal performance of three different Lactobacillus species.Experiments were conducted in vitro and in situ to extend the shelf life of wheat bread. Standard sourdough analyses were performed characterising acidity and carbohydrate levels. Overall, the strains showed good inhibition in vitro against the indicator mould Fusarium culmorum TMW4.2043. Sourdough bread fermented with Lactobacillus amylovorus DSM19280 performed best in the in situ shelf life experiment. An average shelf life extension of six more mould-free days was reached when compared to the non-acidified control bread. A range of antifungal-active acids like 3-phenyllactic acid, 4-hydroxyphenyllactic acid and 2-hydroxyisocaproic acid in quantities between 0.1 and 360 mg/kg were present in the freeze-dried sourdoughs. Their concentration differed greatly amongst the species.However, a higher concentration of these compounds could not completely justify the growth inhibition of environmental moulds. In particular, although Lb. reuteri R29 produced the highest total concentration of these active compounds in the sourdough, its addition to bread did not result in a longest shelf life. Nevertheless, when the artificial compounds were spiked into a chemically acidified dough, it succeeded in a longer shelf life (+25 %) than achieved only by acidifying the dough. This provides evidence of their contribution to the antifungal activity and their synergy in concentration levels far below their single minimal inhibition concentrations under acidic conditions. PMID:26481620

  11. Some Antifungal Properties of Sorbic Acid Extracted from Berries of Rowan (Sorbus Aucuparia).

    ERIC Educational Resources Information Center

    Brunner, Ulrich

    1985-01-01

    The food preservative sorbic acid can be extracted from Eurasian mountain ash berries (commercially available) and used to show antifungal properties in microbiological investigations. Techniques for extraction, purification, ultraviolet analysis, and experiments displaying antifungal activity are described. A systematic search for similar…

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

    PubMed

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

    2014-08-01

    Strain HD1 with antifungal activity was isolated from kimchi and identified as Lactobacillus plantarum. Antifungal compounds from Lb. plantarum HD1 were active against food- and feed-borne filamentous fungi and yeasts in a spot-on-the-lawn assay. Antifungal activity of Lb. plantarum HD1 was stronger against filamentous fungi than yeast. Antifungal compounds were purified using solid phase extraction (SPE) and recycling preparative-HPLC. Structures of the antifungal compounds were elucidated by electrospray ionization-mass spectrometry and nuclear magnetic resonance. Active compounds from Lb. plantarum HD1 were identified as 5-oxododecanoic acid (MW 214), 3-hydroxy decanoic acid (MW 188), and 3-hydroxy-5-dodecenoic acid (MW 214). To investigate the potential application of these antifungal compounds for reduction of fungal spoilage in foods, Korean draft rice wine was used as a food model. White film-forming yeasts were observed in control draft rice wine after 11 days of incubation. However, film-forming yeasts were not observed in draft rice wine treated with SPE-prepared culture supernatant of Lb. plantarum HD1 (equivalent to 2.5% addition of culture supernatant) until 27 days of incubation. The addition of antifungal compounds to Korean draft rice wine extended shelf-life up to 27 days at 10 °C without any sterilization process. Therefore, the antifungal activity of Lb. plantarum HD1 may lead to the development of powerful biopreservative systems capable of preventing food- and feed-borne fungal spoilage. PMID:24750809

  13. Antifungal activities of the leaves of three Pistacia species grown in Turkey.

    PubMed

    Kordali, S; Cakir, A; Zengin, H; Duru, M E

    2003-02-01

    The crude extracts obtained from the leaves of Pistacia vera, Pistacia terebinthus and Pistacia lentiscus were tested for antifungal activities against three pathogenic agricultural fungi, Phythium ultimum, Rhizoctania solani and Fusarium sambucinum. The extracts significantly inhibited the growth of P. ultimum and R. solani. However, the antifungal activity was not observed against F. sambucinum. PMID:12628416

  14. Anti-fungal activities of medicinal plants extracts of Ivorian pharmacopoeia

    PubMed Central

    Mathieu, Kra Adou Koffi; Marcel, Ahon Gnamien; Djè, Djo-Bi; Sitapha, Ouattara; Adama, Coulibaly; Joseph, Djaman Allico

    2014-01-01

    Aim: This study was to evaluate in vitro anti-fungal activity of aqueous and hydroethanolic from medicinal plants extracts collected in Côte d’Ivoire. Materials and Methods: Plants extracts were prepared by homogenization and separately incorporated to Sabouraud agar using the agar slanted double dilution method. Ketoconazole was used as standards for anti-fungal assay. The anti-fungal tests were performed by sowing 1000 cells of Candida albicans on the previously prepared medium culture. Anti-fungal activity was determined by evaluating anti-fungal parameters values (minimal fungicidal concentrations [MFC] and IC50). Results: The results showed that all extracts possessed anti-fungal activities whose levels vary from plant species to another. Eight of them had a satisfactory anti-candidosic activity and extracts from Terminalia species were the most active. Among them the Terminalia superba extracts generated the strongest activities (MFC = 0.0975 mg/mL). Compared with ketoconazole (MFC = 0.390 mg/mL), the T. superba extracts, aqueous (MFC = 0.195 mg/mL) and hydroethanolic (0.0975 mg/mL) were successively twice and four times more active. The worst anti-fungal activity (MFC = 1600 mg/mL) was obtained with the Guarea cedrata aqueous extract. Conclusion: All medicinal plants extracts produced anti-fungal activities, and T. superba was the most active. PMID:26401367

  15. Antifungal activity of the essential oil from Calendula officinalis L. (asteraceae) growing in Brazil

    PubMed Central

    Gazim, Zilda Cristiane; Rezende, Claudia Moraes; Fraga, Sandra Regina; Svidzinski, Terezinha Inez Estivaleti; Cortez, Diógenes Aparicio Garcia

    2008-01-01

    This study tested in vitro activity of the essential oil from flowers of Calendula officinalis using disk-diffusion techniques. The antifungal assay results showed for the first time that the essential oil has good potential antifungal activity: it was effective against all 23 clinical fungi strains tested. PMID:24031180

  16. Optimization of Spore and Antifungal Lipopeptide Production during the Solid State Fermentation of Bacillus subtilis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacillus subtilis strain TrigoCor 1448 was grown on wheat middlings in 0.5-liter solid state fermentation (SSF) bioreactors for the production of an antifungal biological control agent. Total antifungal activity was quantified using a 96-well microplate bioassay against the plant pathogen Fusarium ...

  17. Antifungal activities of Hedychium essential oils and plant extracts against mycotoxigenic fungi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant-derived antifungal compounds are preferred to chemicals to reduce the risk of toxic effects on humans, livestock and the environment. Essential oil extracted from rhizomes and plant extracts of ornamental ginger lily (Hedychium spp.) were evaluated for their antifungal activity against two fu...

  18. Antifungal compounds from turmeric and nutmeg with activity against plant pathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The antifungal activity of twenty-two common spices was evaluated against plant pathogens using direct-bioautography coupled Colletotrichum bioassays. Turmeric, nutmeg, ginger, clove, oregano, cinnamon, anise, fennel, basil, black cumin, and black pepper showed antifungal activity against the plant ...

  19. Augmenting antifungal activity of oxidizing agent with kojic acid: Control of Penicillium strains infecting crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative treatment is a strategy for preventing Penicillium contamination in foods or crops. Antifungal efficacy of oxidant [hydrogen peroxide (H2O2)], biotic effector [kojic acid (KA)] and abiotic stress (heat), alone or in combination, was investigated in Penicillium. The levels of antifungal int...

  20. Thiophene congeners of morpholine and allylamine type antifungals--syntheses and biological activities.

    PubMed

    Bracher, F; Papke, T

    1995-08-01

    A thiophene analogue 8 of the antifungal drug amorolfine (1) was prepared starting from the alcohol 5. In addition, congeners of naftifine, terbinafine and butenafine, in which the naphthalene ring is replaced by a branched thienylalkyl group, wee synthesized. Of the four drug analogues only compound 9, related to terbinafine, showed significant antifungal activity. PMID:7568314

  1. Antifungal, mosquito deterrent, and larvicidal activity of N-(benzylidene)-3-cyclohexylpropionic acid hydrazide derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydrazone derivatives possess good antifungal and insecticidal activities and their structure are used in pesticide design. In the present study, ten hydrazone derivatives (2a-j) were evaluated for their antifungal activity against Colletotrichum, Botrytis, Fusarium and Phomopsis species and for the...

  2. Antifungal activity of gold nanoparticles prepared by solvothermal method

    SciTech Connect

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

    2013-01-15

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

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

    PubMed

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

    2015-01-01

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

  4. Antifungal activity of the local complement system in cerebral aspergillosis.

    PubMed

    Rambach, Günter; Hagleitner, Magdalena; Mohsenipour, Iradj; Lass-Flörl, Cornelia; Maier, Hans; Würzner, Reinhard; Dierich, Manfred P; Speth, Cornelia

    2005-10-01

    Dissemination of aspergillosis into the central nervous system is associated with nearly 100% mortality. To study the reasons for the antifungal immune failure we analyzed the efficacy of cerebral complement to combat the fungus Aspergillus. Incubation of Aspergillus in non-inflammatory cerebrospinal fluid (CSF) revealed that complement levels were sufficient to obtain a deposition on the surface, but opsonization was much weaker than in serum. Consequently complement deposition from normal CSF on fungal surface stimulated a very low phagocytic activity of microglia, granulocytes, monocytes and macrophages compared to stimulation by conidia opsonized in serum. Similarly, opsonization of Aspergillus by CSF was not sufficient to induce an oxidative burst in infiltrating granulocytes, whereas conidia opsonized in serum induced a clear respiratory signal. Thus, granulocytes were capable of considerably reducing the viability of serum-opsonized Aspergillus conidia, but not of conidia opsonized in CSF. The limited efficacy of antifungal attack by cerebral complement can be partly compensated by enhanced synthesis, leading to elevated complement concentrations in CSF derived from a patient with cerebral aspergillosis. This inflammatory CSF was able to induce (i) a higher complement deposition on the Aspergillus surface than non-inflammatory CSF, (ii) an accumulation of complement activation products and (iii) an increase in phagocytic and killing activity of infiltrating granulocytes. However, levels and efficacy of the serum-derived complement were not reached. These data indicate that low local complement synthesis and activation may represent a central reason for the insufficient antifungal defense in the brain and the high mortality rate of cerebral aspergillosis. PMID:16027023

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

    PubMed

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

    2016-08-01

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

  6. Heterologous expression of new antifungal chitinase from wheat.

    PubMed

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

    2007-11-01

    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

  7. New ethacridine derivatives as the potential antifungal and antibacterial preparations.

    PubMed

    Petrikaite, Vilma; Tarasevicius, Eduardas; Pavilonis, Alvydas

    2007-01-01

    Until the 20th century fungal infections were rather easy cured, and the need of new antifungal drugs was low. However, low choice of antifungal preparations, their toxicity, limited spectrum of action, and ability to produce resistant strains show the need of new effective medicines for systemic fungal diseases in nowadays. Our goal of research was to synthesize new antimicrobial compounds containing three or more pharmacophores in one molecule. The initial 5-substituted-2-methylmercaptothiazolidin-4-ones were subjected to S-demethylation to yield 2-amino-substituted thiazolidinones. Ethacridine, nitrofuran aldehydes and nitrobenzene aldehyde as pharmacophoric amino or aldehyde group having compounds have been used. Antimicrobial (antifungal) activity of the new compounds was screened in vitro in these bacterial cultures: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Klebsiella pneumoniae ATCC 33499 and fungal cultures: Candida albicans ATCC 60193, Candida glabrata, Candida krusei, Candida kefyr ATCC 8614, Candida tropicalis ATCC 8302, Candida parapsilosis. Results showed that the new compounds were significantly more effective as antimicrobial agents than initial preparation ethacridine. Ethacridine derivatives were not only effective against numerous gram-positive and some gram-negative bacteria, but the spectrum of action has been discovered against fungi. Minimal fungistatic concentration varies in the range 10.0-750 microg/mL and antibacterial concentration is in the range 62.5-1000 microg/mL. Compound 2a having nitrofuryl substituent in the fifth position of tiazolidine cycle was the most active of synthesized ethacridine compounds. The obtained results gave the opportunity to separate the perspective group of potential antiinfective compounds. PMID:17895642

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

    PubMed

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

    2014-01-01

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

  9. Characterization of a new antifungal lipid transfer protein from wheat.

    PubMed

    Kirubakaran, S Isaac; Begum, S Mubarak; Ulaganathan, K; Sakthivel, N

    2008-10-01

    Lipid transfer proteins (LTPs) are members of the family of pathogenesis-related proteins (PR-14) that are believed to be involved in plant defense responses. In this study, a novel gene Ltp 3F1 encoding an antifungal protein from wheat (Sumai 3) was subcloned, overexpressed in Escherichia coli BL-21 (DE3) and enriched using ammonium sulfate fractionation followed by gel permeation chromatography. Molecular phylogeny analyses of wheat Ltp 3F1 gene showed a strong identity to other plant LTPs. Predicted three-dimensional structural model showed the presence of 6 alpha-helices and 9 loop turns. The active site catalytic residues Gly30, Pro50, Ala52 and Cys55 may be suggested for catalyzing the reaction involved in lipid binding. SDS-PAGE analysis confirmed the production of recombinant fusion protein. The LTP fusion protein exhibited a broad-spectrum antifungal activity against Alternaria sp., Rhizoctonia solani, Curvularia lunata, Bipolaris oryzae, Cylindrocladium scoparium, Botrytis cinerea and Sarocladium oryzae. Gene cassette with cyanamide hydratase (cah) marker and Ltp 3F1 gene was constructed for genetic transformation in tobacco. Efficient regeneration was achieved in selective media amended with cyanamide. Transgenic plants with normal phenotype were obtained. Results of PCR and Southern, Northern and Western hybridization analyses confirmed the integration and expression of genes in transgenic plants. Experiments with detached leaves from transgenic tobacco expressing Ltp 3F1 gene showed fungal resistance. Due to the innate potential of broad-spectrum antifungal activity, wheat Ltp 3F1 gene can be used to enhance resistance against fungi in crop plants. PMID:18595724

  10. Antifungal and Antioxidant Activities of Pyrrolidone Thiosemicarbazone Complexes

    PubMed Central

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

    2012-01-01

    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. PMID:22400016

  11. Antifungal and antibacterial naphthoquinones from Newbouldia laevis roots.

    PubMed

    Gafner, S; Wolfender, J L; Nianga, M; Stoeckli-Evans, H; Hostettmann, K

    1996-07-01

    From a dichloromethane extract of Newbouldia laevis roots, four new (6-hydroxydehydroiso-alpha-lapachone, 7-hydroxydehydroiso-alpha-lapachone, 5,7-dihydroxydehydroiso-alpha-lapachone and 3-hydroxy-5-methoxydehydroiso-alpha-lapachone) and six known naphthoquinones have been isolated. Their structures were established by spectroscopic methods (UV, EI mass spectrometry, 1H and 13C NMR) and that of 7-hydroxydehydroiso-alpha-lapachone was confirmed by X-ray crystallography. All naphthoquinones showed antifungal activity against Cladosporium cucumerinum and Candida albicans, and activity against the bacteria Bacillus subtilis and Escherichia coli. PMID:9397206

  12. An antifungal naphthoquinone, xanthones and secoiridoids from Swertia calycina.

    PubMed

    Rodriguez, S; Wolfender, J L; Hakizamungu, E; Hostettmann, K

    1995-08-01

    A chemical and biological screening of 25 species of the Gentianaceae family has been undertaken. Both methanolic and dichloromethane extracts of Swertia calycina exhibited a strong antifungal activity against Cladosporium cucumerinum and Candida albicans. The compound responsible for this activity has been isolated and identified as 2-methoxy-1,4-naphthoquinone. It is the first naphthoquinone to be described in Gentianaceae species. LC-UV and LC-TSP-MS analysis of the crude extracts of Swertia calycina also allowed on-line identification of six known xanthones and secoiridoids. PMID:7480185

  13. 3-Methoxysampangine, a novel antifungal copyrine alkaloid from Cleistopholis patens.

    PubMed

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

    1990-04-01

    Further examination of the active ethanolic extract of the root bark of Cleistopholis patens by using bioassay-directed fractionation resulted in the isolation of a new alkaloid, 3-methoxysampangine (compound I), together with three known alkaloids, eupolauridine (compound II), liriodenine (compound III), and eupolauridine N-oxide (compound IV). The proposed structure of compound I was based on its physicochemical properties and spectral data. 3-Methoxysampangine exhibited significant antifungal activity against Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. This is the first report of the isolation of liriodenine (compound III) from the root bark of C. patens. PMID:2188584

  14. 3-Methoxysampangine, a novel antifungal copyrine alkaloid from Cleistopholis patens.

    PubMed Central

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

    1990-01-01

    Further examination of the active ethanolic extract of the root bark of Cleistopholis patens by using bioassay-directed fractionation resulted in the isolation of a new alkaloid, 3-methoxysampangine (compound I), together with three known alkaloids, eupolauridine (compound II), liriodenine (compound III), and eupolauridine N-oxide (compound IV). The proposed structure of compound I was based on its physicochemical properties and spectral data. 3-Methoxysampangine exhibited significant antifungal activity against Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. This is the first report of the isolation of liriodenine (compound III) from the root bark of C. patens. PMID:2188584

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

    PubMed

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

    2015-04-15

    A new decalin derivative, trichoharzianol (1), together with three known compounds, eujavanicol A (2), 5-hydroxy-3-hydroxymethyl-2-methyl-7-methoxychromone (3), and 4,6-dihydroxy-5-methylphthalide (4), were isolated from Trichoderma harzianum F031. For the first time, compounds 2-4 were reported from the Trichoderma species. Their structures were characterized by spectroscopic methods. Trichoharzianol (1) showed the highest antifungal activity against Colletotrichum gloeosporioides, with a minimum inhibitory concentration (MIC) of 128 μg/mL. PMID:25817439

  16. Azole antifungal agents related to naftifine and butenafine.

    PubMed

    Castellano, S; La Colla, P; Musiu, C; Stefancich, G

    2000-06-01

    The methyl group of naftifine (1) and butenafine (2) was replaced by an azolic nucleus to obtain the new compounds 3-8 which exhibit the characteristics of both allylamine (or benzylamine) and azole antifungals. The title compounds were evaluated in vitro against several pathogenic fungi responsible for human disease. Among these, compounds 5, 6, and 8 were found to inhibit the growth of dermatophytes with a potency comparable to that of naftifine. The synthetic sequence includes the preparation of aminoazole Schiff bases, reduction, and alkylation of the corresponding secondary amines. PMID:10909187

  17. Mechanism of Action of Efinaconazole, a Novel Triazole Antifungal Agent

    PubMed Central

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

    2013-01-01

    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 4α-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 14α-demethylase inhibition, leading to secondary degenerative changes. PMID:23459486

  18. Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy

    PubMed Central

    Asner, Sandra A.; Giulieri, Stefano; Diezi, Manuel; Marchetti, Oscar

    2015-01-01

    Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during therapy with amphotericin B (AMB), caspofungin (CAS), and azoles for treatment of persistent candidemia in an immunocompromised child with severe enterocolitis and visceral adenoviral disease. As documented from restriction fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD) analysis, the five C. lusitaniae isolates examined were related to each other. From antifungal susceptibility and molecular analyses, 5 different profiles (P) were obtained. These profiles included the following: profile 1 (P1) (CAS MIC [μg/ml], 0.5; fluconazole [FLC] MIC, 0.25), determined while the patient was being treated with liposomal AMB for 3 months; P2 (FLC MIC [μg/ml], 0.25; CAS MIC, 4), while the patient was being treated with CAS for 2 weeks; P3 (CAS MIC [μg/ml], 0.5; FLC MIC, 32), while the patient was being treated with azoles and CAS initially followed by azoles alone for a week; P4 (CAS MIC [μg/ml], 8; FLC MIC, 8), while the patient was being treated with both drugs for 3 weeks; and P5 (AMB MIC [μg/ml], 0.125; CAS MIC, 8), while the patient was being treated with AMB and FLC for 2 weeks. CAS resistance was associated with resistance not only to micafungin and anidulafungin but also to AMB. Analysis of CAS resistance revealed 3 novel FKS1 mutations in CAS-resistant isolates (S638Y in P2; S631Y in P4; S638P in P5). While S638Y and -P are within HS1, S631Y is in close proximity to this domain but was confirmed to confer candin resistance using a site-directed mutagenesis approach. FLC resistance could be linked with overexpression of major facilitator gene 7 (MFS7) in C. lusitaniae P2 and P4 and was associated with resistance to 5

  19. The effects of Paenibacillus polymyxa E681 on antifungal and crack remediation of cement paste.

    PubMed

    Park, Sung-Jin; Park, Seung-Hwan; Ghim, Sa-Youl

    2014-10-01

    This study investigated the antifungal effects of cement paste containing Paenibacillus polymyxa E681 against Aspergillus niger, a deleterious fungus commonly found in cement buildings and structures. To test the antifungal effects, cement paste containing P. polymyxa E681 was neutralized by CO2 gas, and the fungal growth inhibition was examined according to the clear zone around the cement specimen. In addition to the antifungal effects of the cement paste added with bacteria, calcium crystal precipitation of P. polymyxa E681 was examined by qualitative and quantitative analyses. The cement paste containing P. polymyxa E681 showed strong antifungal effects but fusA mutant (deficient in fusaricidin synthesis) showed no antifungal activity. Crack sealing of the cement paste treated with P. polymyxa E681 was captured by light microscope showed fungal growth inhibition and crack repairing in cement paste. PMID:24824950

  20. Detection and partial characterization of antifungal bioactivity from the secretions of the medicinal maggot, Lucilia sericata.

    PubMed

    Evans, Rhys; Dudley, Ed; Nigam, Yamni

    2015-01-01

    The antibacterial properties of the excretions/secretions (ES) of the medicinal maggot, Lucilia sericata have long been known and the effectiveness of maggot debridement therapy in relation to the clearance of bacteria from the surface of wounds has been the source of much research over recent years. Less well known, however, are the antifungal properties of L. sericata ES. Here, we show by means of the colony forming unit assay and optical density assays, that L. sericata native ES possess significant antifungal properties and appears to possess a highly heat stable, freeze/thaw, and lyophilization resistant antifungal component. We also show that the antifungal activity present in the native ES consists of a number of antifungal components present in three fraction masses consisting of >10, 10-0.5, and <0.5 kDa, with the greatest level of activity being seen in the <0.5 kDa fraction. PMID:25847128

  1. An overview about the medical use of antifungals in Portugal in the last years.

    PubMed

    Manuel da S Azevedo, Maria; Cruz, Luisa; Pina-Vaz, Cidália; Gonçalves-Rodrigues, Acácio

    2016-05-01

    Despite the introduction of new antifungal agents, the frequency of invasive and mucocutaneous fungal infections as well as resistance to antifungal drugs continues to increase. Over 300 million persons are infected annually with fungi. Resistance to antimicrobials is one of today's major health threats. Can the possible causes of fungal antimicrobial resistance be understood and prevented to minimize risks to public health. We provide an overview of antifungal drug use in European countries, particularly Portugal. We reviewed prescriptions for and over-the-counter sales (OTC) of azoles in Portuguese pharmacies and in alternative shops. We conclude that in Portugal, azole antifungal sales, as well as medical prescribed azoles are very high. The Portuguese population consumes more antifungal drugs per capita than others in Europe. PMID:26865319

  2. Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans

    PubMed Central

    Cui, Jinhui; Ren, Biao; Tong, Yaojun; Dai, Huanqin; Zhang, Lixin

    2015-01-01

    Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi-drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections. PMID:26048362

  3. 76 FR 27261 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ... Federal Register of March 19, 2010 (75 FR 13277) (FRL-8813- 2), EPA issued a notice pursuant to section... numerous previous occasions. Refer to Federal Register 70 FR 37686, June 30, 2005; 70 FR 1354, January 7, 2005; 69 FR 63096, October 29, 2004 for the Agency's response to these objections. V....

  4. 77 FR 38199 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ....gov/dockets . II. Summary of Petitioned-For Tolerances In the Federal Register of July 20, 2011 (76 FR... Register of Wednesday, May 11, 2011 (76 FR 27261) (FRL-8873-2). C. Exposure Assessment 1. Dietary exposure... Executive Order 12866, entitled ``Regulatory Planning and Review'' (58 FR 51735, October 4, 1993)....

  5. 77 FR 75039 - Propiconazole; Pesticide Tolerances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    .... Summary of Petitioned-for Tolerance In the Federal Register of November 9, 2011 (Volume 76, FR 69690) (FRL..., 2011 (76 FR 27261) (FRL-8873-2). C. Exposure Assessment 1. Dietary exposure from food and feed uses. In..., entitled ``Regulatory Planning and Review'' (58 FR 51735, October 4, 1993). Because this final rule...

  6. Differential antifungal and calcium channel-blocking activity among structurally related plant defensins.

    PubMed

    Spelbrink, Robert G; Dilmac, Nejmi; Allen, Aron; Smith, Thomas J; Shah, Dilip M; Hockerman, Gregory H

    2004-08-01

    Plant defensins are a family of small Cys-rich antifungal proteins that play important roles in plant defense against invading fungi. Structures of several plant defensins share a Cys-stabilized alpha/beta-motif. Structural determinants in plant defensins that govern their antifungal activity and the mechanisms by which they inhibit fungal growth remain unclear. Alfalfa (Medicago sativa) seed defensin, MsDef1, strongly inhibits the growth of Fusarium graminearum in vitro, and its antifungal activity is markedly reduced in the presence of Ca(2+). By contrast, MtDef2 from Medicago truncatula, which shares 65% amino acid sequence identity with MsDef1, lacks antifungal activity against F. graminearum. Characterization of the in vitro antifungal activity of the chimeras containing portions of the MsDef1 and MtDef2 proteins shows that the major determinants of antifungal activity reside in the carboxy-terminal region (amino acids 31-45) of MsDef1. We further define the active site by demonstrating that the Arg at position 38 of MsDef1 is critical for its antifungal activity. Furthermore, we have found for the first time, to our knowledge, that MsDef1 blocks the mammalian L-type Ca(2+) channel in a manner akin to a virally encoded and structurally unrelated antifungal toxin KP4 from Ustilago maydis, whereas structurally similar MtDef2 and the radish (Raphanus sativus) seed defensin Rs-AFP2 fail to block the L-type Ca(2+) channel. From these results, we speculate that the two unrelated antifungal proteins, KP4 and MsDef1, have evolutionarily converged upon the same molecular target, whereas the two structurally related antifungal plant defensins, MtDef2 and Rs-AFP2, have diverged to attack different targets in fungi. PMID:15299136

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

    PubMed Central

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

    2012-01-01

    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. PMID:22539027

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

    PubMed

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

    2011-03-15

    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 μM, 10 μM, 80 μM, 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 μM. 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

  9. ANTIFUNGAL POTENTIAL OF PLANT SPECIES FROM BRAZILIAN CAATINGA AGAINST DERMATOPHYTES.

    PubMed

    Biasi-Garbin, Renata Perugini; Demitto, Fernanda de Oliveira; Amaral, Renata Claro Ribeiro do; Ferreira, Magda Rhayanny Assunção; Soares, Luiz Alberto Lira; Svidzinski, Terezinha Inez Estivalet; Baeza, Lilian Cristiane; Yamada-Ogatta, Sueli Fumie

    2016-01-01

    Trichophyton rubrum and Trichophyton mentagrophytes complex, or Trichophyton spp. are the main etiologic agents of dermatophytosis, whose treatment is limited by the high cost of antifungal treatments, their various side effects, and the emergence of resistance amongst these species. This study evaluated the in vitro antidermatophytic activity of 23 crude extracts from nine plant species of semiarid vegetation (caatinga) found in Brazil. The extracts were tested at concentrations ranging from 1.95 to 1,000.0 mg/mL by broth microdilution assay against the reference strains T. rubrum ATCC 28189 and T. mentagrophytes ATCC 11481, and 33 clinical isolates of dermatophytes. All plants showed a fungicidal effect against both fungal species, with MIC/MFC values of the active extracts ranging from 15.6 to 250.0 µg/mL. Selected extracts of Eugenia uniflora (AcE), Libidibia ferrea (AE), and Persea americana (AcE) also exhibited a fungicidal effect against all clinical isolates of T. rubrum and T. mentagrophytes complex. This is the first report of the antifungal activity of Schinus terebinthifolius, Piptadenia colubrina, Parapiptadenia rigida, Mimosa ophthalmocentra, and Persea americana against both dermatophyte species. PMID:27007561

  10. Structural Basis of Human CYP51 Inhibition by Antifungal Azoles

    SciTech Connect

    Strushkevich, Natallia; Usanov, Sergey A.; Park, Hee-Won

    2010-09-22

    The obligatory step in sterol biosynthesis in eukaryotes is demethylation of sterol precursors at the C14-position, which is catalyzed by CYP51 (sterol 14-alpha demethylase) in three sequential reactions. In mammals, the final product of the pathway is cholesterol, while important intermediates, meiosis-activating sterols, are produced by CYP51. Three crystal structures of human CYP51, ligand-free and complexed with antifungal drugs ketoconazole and econazole, were determined, allowing analysis of the molecular basis for functional conservation within the CYP51 family. Azole binding occurs mostly through hydrophobic interactions with conservative residues of the active site. The substantial conformational changes in the B{prime} helix and F-G loop regions are induced upon ligand binding, consistent with the membrane nature of the protein and its substrate. The access channel is typical for mammalian sterol-metabolizing P450 enzymes, but is different from that observed in Mycobacterium tuberculosis CYP51. Comparison of the azole-bound structures provides insight into the relative binding affinities of human and bacterial P450 enzymes to ketoconazole and fluconazole, which can be useful for the rational design of antifungal compounds and specific modulators of human CYP51.

  11. Lipidome analysis reveals antifungal polyphenol curcumin affects membrane lipid homeostasis.

    PubMed

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

    2012-01-01

    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 phosphoglycerides (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 delta 5, 6 desaturase (ERG3) resulting in depletion of ergosterol. This results in parallel accumulation of ergosterol biosynthetic precursors, generation of reactive oxygen species (ROS) and cell death. PMID:22201946

  12. Novel, Synergistic Antifungal Combinations that Target Translation Fidelity

    PubMed Central

    Moreno-Martinez, Elena; Vallieres, Cindy; Holland, Sara L.; Avery, Simon V.

    2015-01-01

    There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ≥8-fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone. PMID:26573415

  13. A novel antifungal protein of Bacillus subtilis B25.

    PubMed

    Tan, Zhiqiong; Lin, Baoying; Zhang, Rongyi

    2013-01-01

    Bacillus subtilis B25 was isolated from banana rhizosphere soil. It has been confirmed for B25 to have stronger antagonism against Fusarium oxysporum f.sp.cubense, Additionally B25 has good inhibitory to plant pathogens, including Corynespora cassiicola, Alternaria solani, Botrytis cinerea and Colletotrichum gloeosporioides on potato dextrose agar (PDA) plates. The antagonistic substance can be extracted from cell-free culture broth supernatants by 70% (w/v) (NH4)2 SO4 saturation. Clear blank band was observed between the protein and a pathogen. The examination of antagonistic mechanism under light microscope showed that the antifungal protein of B25 appeared to inhibit pathogens by leading to mycelium and spores tumescence, distortion, abnormality. The isolation procedure comprised ion exchange chromatography on DEAE-Sephadex Fast Flow and gel filtration chromatography on SephadexG-100. The purified antifungal fraction showed a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The active fraction was identified by NanoLC-ESI-MS/MS The amino acid sequences of 17 peptides segments were obtained. The analysis of the protein suggested that it was a hypothetical protein (gi154685475), with a relative molecular mass of 38708.67 Da and isoelectric point (pI) of 5.63. PMID:24255843

  14. Novel, Synergistic Antifungal Combinations that Target Translation Fidelity.

    PubMed

    Moreno-Martinez, Elena; Vallieres, Cindy; Holland, Sara L; Avery, Simon V

    2015-01-01

    There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ≥8-fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone. PMID:26573415

  15. Onychomycosis: Potential of Nail Lacquers in Transungual Delivery of Antifungals.

    PubMed

    Akhtar, Nida; Sharma, Hemlata; Pathak, Kamla

    2016-01-01

    Onychomycosis constitutes the most common fungal infection of the nail (skin beneath the nail bed) that affects the finger as well as toe nails. It is an infection that is initiated by yeasts, dermatophytes, and nondermatophyte molds. Nail lacquers are topical solutions intended only for use on fingernails as well as toenails and have been found to be useful in the treatment of onychomycosis. Thus, in the present review an attempt has been made to focus on the treatment aspects of onychomycosis and the ungual delivery of antifungals via nail lacquer. Several patents issued on nail lacquer till date have also been discussed. Penetration efficiency was assessed by several researchers across the human nail plate to investigate the potentiality of nail lacquer based formulations. Various clinical trials have also been conducted in order to evaluate the safety and efficacy of nail lacquers in delivering antifungal agents. Thus, it can be concluded that nail lacquer based preparations are efficacious and stable formulations. These possess tremendous potential for clinical topical application to the nail bed in the treatment of onychomycosis. PMID:27123362

  16. Onychomycosis: Potential of Nail Lacquers in Transungual Delivery of Antifungals

    PubMed Central

    Sharma, Hemlata; Pathak, Kamla

    2016-01-01

    Onychomycosis constitutes the most common fungal infection of the nail (skin beneath the nail bed) that affects the finger as well as toe nails. It is an infection that is initiated by yeasts, dermatophytes, and nondermatophyte molds. Nail lacquers are topical solutions intended only for use on fingernails as well as toenails and have been found to be useful in the treatment of onychomycosis. Thus, in the present review an attempt has been made to focus on the treatment aspects of onychomycosis and the ungual delivery of antifungals via nail lacquer. Several patents issued on nail lacquer till date have also been discussed. Penetration efficiency was assessed by several researchers across the human nail plate to investigate the potentiality of nail lacquer based formulations. Various clinical trials have also been conducted in order to evaluate the safety and efficacy of nail lacquers in delivering antifungal agents. Thus, it can be concluded that nail lacquer based preparations are efficacious and stable formulations. These possess tremendous potential for clinical topical application to the nail bed in the treatment of onychomycosis. PMID:27123362

  17. Antifungal activity of lectins against yeast of vaginal secretion

    PubMed Central

    Gomes, Bruno Severo; Siqueira, Ana Beatriz Sotero; de Cássia Carvalho Maia, Rita; Giampaoli, Viviana; Teixeira, Edson Holanda; Arruda, Francisco Vassiliepe Sousa; do Nascimento, Kyria Santiago; de Lima, Adriana Nunes; Souza-Motta, Cristina Maria; Cavada, Benildo Sousa; Porto, Ana Lúcia Figueiredo

    2012-01-01

    Lectins are carbohydrate-binding proteins of non-imune origin. This group of proteins is distributed widely in nature and they have been found in viruses, microorganisms, plants and animals. Lectins of plants have been isolated and characterized according to their chemical, physical-chemical, structural and biological properties. Among their biological activities, we can stress its fungicidal action. It has been previously described the effect of the lectins Dviol, DRL, ConBr and LSL obtained from the seeds of leguminous plants on the growth of yeasts isolated from vaginal secretions. In the present work the experiments were carried out in microtiter plates and the results interpreted by both methods: visual observations and a microplate reader at 530nm. The lectin concentrations varied from 0.5 to 256μg/mL, and the inoculum was established between 65-70% of trammitance. All yeast samples isolated from vaginal secretion were evaluated taxonomically, where were observed macroscopic and microscopic characteristics to each species. The LSL lectin did not demonstrate any antifungal activity to any isolate studied. The other lectins DRL, ConBr and DvioL, showed antifungal potential against yeast isolated from vaginal secretion. These findings offering offer a promising field of investigation to develop new therapeutic strategies against vaginal yeast infections, collaborating to improve women's health. PMID:24031889

  18. ANTIFUNGAL POTENTIAL OF PLANT SPECIES FROM BRAZILIAN CAATINGA AGAINST DERMATOPHYTES

    PubMed Central

    BIASI-GARBIN, Renata Perugini; DEMITTO, Fernanda de Oliveira; do AMARAL, Renata Claro Ribeiro; FERREIRA, Magda Rhayanny Assunção; SOARES, Luiz Alberto Lira; SVIDZINSKI, Terezinha Inez Estivalet; BAEZA, Lilian Cristiane; YAMADA-OGATTA, Sueli Fumie

    2016-01-01

    Trichophyton rubrum and Trichophyton mentagrophytes complex, or Trichophyton spp. are the main etiologic agents of dermatophytosis, whose treatment is limited by the high cost of antifungal treatments, their various side effects, and the emergence of resistance amongst these species. This study evaluated the in vitro antidermatophytic activity of 23 crude extracts from nine plant species of semiarid vegetation (caatinga) found in Brazil. The extracts were tested at concentrations ranging from 1.95 to 1,000.0 mg/mL by broth microdilution assay against the reference strains T. rubrum ATCC 28189 and T. mentagrophytesATCC 11481, and 33 clinical isolates of dermatophytes. All plants showed a fungicidal effect against both fungal species, with MIC/MFC values of the active extracts ranging from 15.6 to 250.0 µg/mL. Selected extracts of Eugenia uniflora (AcE), Libidibia ferrea (AE), and Persea americana (AcE) also exhibited a fungicidal effect against all clinical isolates of T. rubrum and T. mentagrophytes complex. This is the first report of the antifungal activity of Schinus terebinthifolius, Piptadenia colubrina, Parapiptadenia rigida, Mimosa ophthalmocentra, and Persea americana against both dermatophyte species. PMID:27007561

  19. Antifungal Enantiomeric Styrylpyrones from Sanrafaelia ruffonammari and Ophrypetalum odoratum.

    PubMed

    Malebo, Hamisi M; Kihampa, Charles; Mgina, Clarence A; Sung'hwa, Fortunatus; Waibel, Reiner; Jonker, Stephan A; Nkunya, Mayunga H H

    2014-04-01

    Phytochemical investigation of Sanrafaelia ruffonammari Verd and Ophrypetalum odoratum Diels that belongs to the rare genera confined to East African coastal forests led to the isolation of enantiomeric styrylpyrone dimer, (±)-5-methoxy-7-phenyl-[4-methoxy-2-pyronyl]-1-(E)-styryl-2-oxabicyclo-[4.2.0]-octa-4-en-3-one (1) alongside (+)-6-styryl-7,8-epoxy-4-methoxypyran-2-one (2) and the enantiomeric (+)- (3) and (-)-6-styryl-7,8-dihydroxy-4-methoxypyran-2-ones (4). Their structures were established by means of spectroscopic methods. In this paper we reveal for the first time the occurrence of styrylpyrones in East African biodiversity. (+)-6-Styryl-7,8-epoxy-4-methoxypyran-2-one (2) and the dihydroxystyrylpyrone enantiomer (3) showed in vitro antifungal activity against Candida albicans at a concentration of 24.4 and 26.2 µM with zones of inhibition of 17 and 9 mm, respectively. Compound 2 exhibited strong activity in the brine shrimp test with LC50 = 1.7 µg/mL. Their high cytotoxic and antifungal activities render them candidates for further scientific attention for drug development programs against cancer and microbial infections. PMID:24859289

  20. Benzoic acid derivatives with improved antifungal activity: Design, synthesis, structure-activity relationship (SAR) and CYP53 docking studies.

    PubMed

    Berne, Sabina; Kovačič, Lidija; Sova, Matej; Kraševec, Nada; Gobec, Stanislav; Križaj, Igor; Komel, Radovan

    2015-08-01

    Previously, we identified CYP53 as a fungal-specific target of natural phenolic antifungal compounds and discovered several inhibitors with antifungal properties. In this study, we performed similarity-based virtual screening and synthesis to obtain benzoic acid-derived compounds and assessed their antifungal activity against Cochliobolus lunatus, Aspergillus niger and Pleurotus ostreatus. In addition, we generated structural models of CYP53 enzyme and used them in docking trials with 40 selected compounds. Finally, we explored CYP53-ligand interactions and identified structural elements conferring increased antifungal activity to facilitate the development of potential new antifungal agents that specifically target CYP53 enzymes of animal and plant pathogenic fungi. PMID:26154240

  1. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... citations affecting § 180.443, see the List of CFR Sections Affected, which appears in the Finding Aids... Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus...

  2. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus...

  3. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus...

  4. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus...

  5. 40 CFR 180.443 - Myclobutanil; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume... Almond, hulls 2.0 Apple 0.5 Apple, dry pomace 5.0 Apple, wet pomace 5.0 Artichoke, globe 0.90 Asparagus...

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

    PubMed Central

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

    2001-01-01

    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 μg/ml; 48-h MEC, 0.125 μg/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 μg/ml; 48-h MEC, 0.125 μg/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. PMID:11353637

  7. Antifungal treatment in allergic bronchopulmonary aspergillosis with and without cystic fibrosis: a systematic review.

    PubMed

    Moreira, A S; Silva, D; Ferreira, A Reis; Delgado, L

    2014-10-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a rare disease that affects patients with asthma or cystic fibrosis. Its debilitating course has led to the search for new treatments, including antifungals and monoclonal antibodies. To evaluate the efficacy and safety of antifungal treatments in patients with ABPA and either asthma or cystic fibrosis, we performed a systematic review of the literature on the effects of antifungal agents in ABPA using three biomedical databases. Quality assessment was performed using the GRADE methodology and, where appropriate, studies with comparable outcomes were pooled for meta-analysis. Thirty-eight studies - four randomized controlled trials and 34 observational studies - met the eligibility criteria. The antifungal interventions described were itraconazole, voriconazole, posaconazole, ketoconazole, natamycin, nystatin and amphotericin B. An improvement in symptoms, frequency of exacerbations and lung function was reported in most of the studies and was more common with oral azoles. Antifungals also had a positive impact on biomarkers and radiological pulmonary infiltrates, but adverse effects were also common. The quality of the evidence supporting these results was low or very low due to a shortage of controlled studies, heterogeneity between studies and potential bias. Antifungal interventions in ABPA improved patient and disease outcomes in both asthma and cystic fibrosis. However, the recommendation for their use is weak and clinicians should therefore weigh up desirable and undesirable effects on a case-by-case basis. More studies with a better methodology are needed, especially in cystic fibrosis, to increase confidence in the effects of antifungal treatments in ABPA. PMID:24809846

  8. Antifungal susceptibility profiles of 1698 yeast reference strains revealing potential emerging human pathogens.

    PubMed

    Desnos-Ollivier, Marie; Robert, Vincent; Raoux-Barbot, Dorothée; Groenewald, Marizeth; Dromer, Françoise

    2012-01-01

    New molecular identification techniques and the increased number of patients with various immune defects or underlying conditions lead to the emergence and/or the description of novel species of human and animal fungal opportunistic pathogens. Antifungal susceptibility provides important information for ecological, epidemiological and therapeutic issues. The aim of this study was to assess the potential risk of the various species based on their antifungal drug resistance, keeping in mind the methodological limitations. Antifungal susceptibility profiles to the five classes of antifungal drugs (polyens, azoles, echinocandins, allylamines and antimetabolites) were determined for 1698 yeast reference strains belonging to 992 species (634 Ascomycetes and 358 Basidiomycetes). Interestingly, geometric mean minimum inhibitory concentrations (MICs) of all antifungal drugs tested were significantly higher for Basidiomycetes compared to Ascomycetes (p<0.001). Twenty four strains belonging to 23 species of which 19 were Basidiomycetes seem to be intrinsically "resistant" to all drugs. Comparison of the antifungal susceptibility profiles of the 4240 clinical isolates and the 315 reference strains belonging to 53 shared species showed similar results. Even in the absence of demonstrated in vitro/in vivo correlation, knowing the in vitro susceptibility to systemic antifungal agents and the putative intrinsic resistance of yeast species present in the environment is important because they could become opportunistic pathogens. PMID:22396754

  9. A novel 96-well gel-based assay for determining antifungal activity against filamentous fungi.

    PubMed

    Troskie, Anscha Mari; Vlok, Nicolas Maré; Rautenbach, Marina

    2012-12-01

    In recent years the global rise in antibiotic resistance and environmental consciousness lead to a renewed fervour to find and develop novel antibiotics, including antifungals. However, the influence of the environment on antifungal activity is often disregarded and many in vitro assays may cause the activity of certain antifungals to be overestimated or underestimated. The general antifungal test assays that are economically accessible to the majority of scientists primarily rely on visual examination or on spectrophotometric analysis. The effect of certain morphogenic antifungals, which may lead to hyperbranching of filamentous fungi, unfortunately renders these methods unreliable. To minimise the difficulties experienced as a result of hyperbranching, we developed a straightforward, economical 96-well gel-based method, independent of spectrophotometric analysis, for highly repeatable determination of antifungal activity. For the calculation of inhibition parameters, this method relies on the visualisation of assay results by digitisation. The antifungal activity results from our novel micro-gel dilution assay are comparable to that of the micro-broth dilution assay used as standard reference test of The Clinical and Laboratory Standard Institute. Furthermore, our economical assay is multifunctional as it permits microscopic analysis of the preserved assay results, as well as rendering highly reliable data. PMID:23089670

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

    PubMed

    Cordeiro, Rossana de Aguiar; Macedo, Ramila de Brito; Teixeira, Carlos Eduardo Cordeiro; Marques, Francisca Jakelyne de Farias; Bandeira, Tereza de Jesus Pinheiro Gomes; Moreira, José Luciano Bezerra; Brilhante, Raimunda Sâmia Nogueira; Rocha, Marcos Fábio Gadelha; Sidrim, José Júlio Costa

    2014-07-01

    Candida parapsilosis complex comprises three closely related species, C. parapsilosis sensu stricto, Candida metapsilosis and Candida orthopsilosis. In the last decade, antifungal resistance to azoles and caspofungin among C. parapsilosis sensu lato strains has been considered a matter of concern worldwide. In the present study, we evaluated the synergistic potential of antifungals and the calcineurin inhibitor cyclosporin A (Cys) against planktonic and biofilms of C. parapsilosis complex from clinical sources. Susceptibility assays with amphotericin, fluconazole, voriconazole, caspofungin and Cys were performed by microdilution in accordance with Clinical and Laboratory Standards Institute guidelines. Synergy testing against planktonic cells of C. parapsilosis sensu lato strains was assessed by the chequerboard method. Combinations formed by antifungals with Cys were evaluated against mature biofilms in microtitre plates. No differences in the antifungal susceptibility pattern among species were observed, but C. parapsilosis sensu stricto strains were more susceptible to Cys than C. orthopsilosis and C. metapsilosis. Synergism between antifungals and Cys was observed in C. parapsilosis sensu lato strains. Combinations formed by antifungals and Cys were able to prevent biofilm formation and showed an inhibitory effect against mature biofilms of C. parapsilosis sensu stricto, C. metapsilosis and C. orthopsilosis. These results strengthen the potential of calcineurin inhibition as a promising approach to enhance the efficiency of antifungal drugs. PMID:24722799

  11. Antifungal Activity of Bee Venom and Sweet Bee Venom against Clinically Isolated Candida albicans

    PubMed Central

    Lee, Seung-Bae

    2016-01-01

    Objectives: The purpose of this study was to investigate the antifungal effect of bee venom (BV) and sweet bee venom (SBV) against Candida albicans (C. albicans) clinical isolates. Methods: In this study, BV and SBV were examined for antifungal activities against the Korean Collection for Type Cultures (KCTC) strain and 10 clinical isolates of C. albicans. The disk diffusion method was used to measure the antifungal activity and minimum inhibitory concentration (MIC) assays were performed by using a broth microdilution method. Also, a killing curve assay was conducted to investigate the kinetics of the anti- fungal action. Results: BV and SBV showed antifungal activity against 10 clinical isolates of C. albicans that were cultured from blood and the vagina by using disk diffusion method. The MIC values obtained for clinical isolates by using the broth microdilution method varied from 62.5 μg/ mL to 125 μg/mL for BV and from 15.63 μg/mL to 62.5 μg/mL for SBV. In the killing-curve assay, SBV behaved as amphotericin B, which was used as positive control, did. The antifungal efficacy of SBV was much higher than that of BV. Conclusion: BV and SBV showed antifungal activity against C. albicans clinical strains that were isolated from blood and the vagina. Especially, SBV might be a candidate for a new antifungal agent against C. albicans clinical isolates. PMID:27280049

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

    PubMed Central

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

    2014-01-01

    Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use. PMID:24465737

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

    PubMed Central

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

    2013-01-01

    Abstract Candidiasis is the most frequent infection by opportunistic fungi such as Candida albicans, Candida tropicalis, and Candida krusei. Ethanol extract from Eugenia uniflora was assayed, for its antifungal activity, either alone or combined with four selected chemotherapeutic antimicrobial agents, including anphotericin B, mebendazole, nistatin, and metronidazole against these strains. The obtained results indicated that the association of the extract of E. uniflora to metronidazole showed a potential antifungal activity against C. tropicalis. However, no synergistic activity against the other strains was observed, as observed when the extract was associated with the other, not enhancing their antifungal activity. PMID:23819641

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

    PubMed

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

    2013-09-01

    A new carbazole alkaloid named clauraila E (1) together with 8 known compounds were isolated from the methanol extract of the roots of Clausena harmandiana. All compounds were evaluated for antifungal activity against Pythium insidiosum using disc diffusion assay. Pythium insidiosum is a fungus-like microorganism, for which antifungals available now are not effective. It was found that compounds 3, 6, 7 and 9 could inhibit the mycelia growth of P. insidiosum. The results show convincingly that they may be lead to compounds for the development of probiotic or novel antifungal drugs. PMID:23595552

  15. Enhancement of the antifungal activity of antimicrobial drugs by Eugenia uniflora L.

    PubMed

    Santos, Karla K A; Matias, Edinardo F F; Tintino, Saulo R; Souza, Celestina E S; Braga, Maria F B M; Guedes, Gláucia M M; Costa, José G M; Menezes, Irwin R A; Coutinho, Henrique Douglas Melo

    2013-07-01

    Candidiasis is the most frequent infection by opportunistic fungi such as Candida albicans, Candida tropicalis, and Candida krusei. Ethanol extract from Eugenia uniflora was assayed, for its antifungal activity, either alone or combined with four selected chemotherapeutic antimicrobial agents, including anphotericin B, mebendazole, nistatin, and metronidazole against these strains. The obtained results indicated that the association of the extract of E. uniflora to metronidazole showed a potential antifungal activity against C. tropicalis. However, no synergistic activity against the other strains was observed, as observed when the extract was associated with the other, not enhancing their antifungal activity. PMID:23819641

  16. Update from the Laboratory: Clinical Identification and Susceptibility Testing of Fungi and Trends in Antifungal Resistance.

    PubMed

    Albataineh, Mohammad T; Sutton, Deanna A; Fothergill, Annette W; Wiederhold, Nathan P

    2016-03-01

    Despite the availability of new diagnostic assays and broad-spectrum antifungal agents, invasive fungal infections remain a significant challenge to clinicians and are associated with marked morbidity and mortality. In addition, the number of etiologic agents of invasive mycoses has increased accompanied by an expansion in the immunocompromised patient populations, and the use of molecular tools for fungal identification and characterization has resulted in the discovery of several cryptic species. This article reviews various methods used to identify fungi and perform antifungal susceptibility testing in the clinical laboratory. Recent developments in antifungal resistance are also discussed. PMID:26739605

  17. Potential Targets for Antifungal Drug Discovery Based on Growth and Virulence in Candida albicans

    PubMed Central

    Li, Xiuyun; Hou, Yinglong; Yue, Longtao; Liu, Shuyuan; Du, Juan

    2015-01-01

    Fungal infections, especially infections caused by Candida albicans, remain a challenging problem in clinical settings. Despite the development of more-effective antifungal drugs, their application is limited for various reasons. Thus, alternative treatments with drugs aimed at novel targets in C. albicans are needed. Knowledge of growth and virulence in fungal cells is essential not only to understand their pathogenic mechanisms but also to identify potential antifungal targets. This article reviews the current knowledge of the mechanisms of growth and virulence in C. albicans and examines potential targets for the development of new antifungal drugs. PMID:26195510

  18. Acetoxychavicol Acetate, an Antifungal Component of Alpinia galanga1.

    PubMed

    Janssen, A M; Scheffer, J J

    1985-12-01

    The essential oils from fresh and dried rhizomes of ALPINIA GALANGA showed an antimicrobial activity against gram-positive bacteria, a yeast and some dermatophytes, using the agar overlay technique. The main components of the oils were also tested and terpinen-4-ol was found most active. An N-pentane/diethyl ether extract of dried rhizomes was active against TRICHOPHYTON MENTAGROPHYTES. 1'-Acetoxychavicol acetate, 1'-acetoxyeugenol acetate and 1'-hydroxychavicol acetate identified by MS and NMR were found in the antifungally active fractions obtained by LSC. Acetoxychavicol acetate was active against the seven fungi tested and its MIC value for dermatophytes ranged from 50 to 250 microg/ml. Dried sliced rhizomes contained 1.5% of this compound. The compound was not found in rhizomes of ALPINIA OFFICINARUM, ZINGIBER OFFICINALE and KAEMPFERIA GALANGA. PMID:17345272

  19. Antifungal activity of silver nanoparticles obtained by green synthesis.

    PubMed

    Mallmann, Eduardo José J; Cunha, Francisco Afrânio; Castro, Bruno N M F; Maciel, Auberson Martins; Menezes, Everardo Albuquerque; Fechine, Pierre Basílio Almeida

    2015-01-01

    Silver nanoparticles (AgNPs) are metal structures at the nanoscale. AgNPs have exhibited antimicrobial activities against fungi and bacteria; however synthesis of AgNPs can generate toxic waste during the reaction process. Accordingly, new routes using non-toxic compounds have been researched. The proposal of the present study was to synthesize AgNPs using ribose as a reducing agent and sodium dodecyl sulfate (SDS) as a stabilizer. The antifungal activity of these particles against C. albicans and C. tropicalis was also evaluated. Stable nanoparticles 12.5 ± 4.9 nm (mean ± SD) in size were obtained, which showed high activity against Candida spp. and could represent an alternative for fungal infection treatment. PMID:25923897

  20. A lectin with antifungal activity from the mussel Crenomytilus grayanus.

    PubMed

    Chikalovets, Irina V; Chernikov, Oleg V; Pivkin, Mikhail V; Molchanova, Valentina I; Litovchenko, Alina P; Li, Wei; Lukyanov, Pavel A

    2015-02-01

    Lectins (carbohydrate-binding proteins) are well known to actively participate in the defense functions of vertebrates and invertebrates where they play an important role in the recognition of foreign particles. In this study, we investigated of in vitro antifungal activity of lectin from the mussel Crenomytilus grayanus (CGL). Enzyme-linked immunosorbent assay indicated that CGL was predominantly detectable in tissues of mantle and to a lesser degree in the tissues of muscle, hepatopancreas, gill and hemocytes. After challenged by Pichia pastoris the level of CGL was upregulated and reached the maximum level at 12 h post challenge and recovered to the original level at 24 h. The lectin was capable of inhibiting the germination of spores and hyphal growth in the fungi. All these results indicated that CGL is involved in the innate immune response in mollusc animals. PMID:25482060

  1. Partial identification of antifungal compounds from Punica granatum peel extracts.

    PubMed

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

    2012-05-16

    Aqueous extracts of pomegranate peels were assayed in vitro for their antifungal activity against six rot fungi that cause fruit and vegetable decay during storage. The growth rates of Alternaria alternata , Stemphylium botryosum , and Fusarium spp. were significantly inhibited by the extracts. The growth rates were negatively correlated with the levels of total polyphenolic compounds in the extract and particularly with punicalagins, the major ellagitannins in pomegranate peels. Ellagitannins were also found to be the main compounds in the bioactive fractions using bioautograms, and punicalagins were identified as the main bioactive compounds using chromatographic separation. These results suggest that ellagitannins, and more specifically punicalagins, which are the dominant compounds in pomegranate peels, may be used as a control agent of storage diseases and to reduce the use of synthetic fungicides. PMID:22533815

  2. Pavietin, a coumarin from Aesculus pavia with antifungal activity.

    PubMed

    Curir, Paolo; Galeotti, Francesco; Dolci, Marcello; Barile, Elisa; Lanzotti, Virginia

    2007-10-01

    A new prenylated coumarin, S-6-[2-(hydroxymethyl)butoxy]-7-hydroxy-4-methyl-2 H-chromen-2-one ( 1), named pavietin, has been isolated from the leaves of an Aesculus pavia genotype along with three known flavonol glycosides, quercetin 3- O-alpha-rhamnoside (quercitrin, 2), quercetin 3- O-alpha-arabinoside ( 3), and isorhamnetin 3- O-alpha-arabinoside (distichin, 4). The chemical structure of compound 1 was determined by chemical and spectroscopic methods, inclusive of UV, MS, and 1D and 2D NMR experiments. It showed appreciable antimicrobial properties against several pathogens, displaying a significant antifungal activity toward one of the main fungal parasites of Aesculus species, Guignardia aesculi. The same biological tests performed with a mixture of flavonoids 2- 4 resulted in weak or no activity. Compound 1 was undetectable in Aesculus hippocastanum, a closely related species lacking resistance to fungal pathogens. The possible role of 1 in plant resistance is discussed. PMID:17914881

  3. Antifungal Susceptibility Testing: Practical Aspects and Current Challenges

    PubMed Central

    Rex, John H.; Pfaller, Michael A.; Walsh, Thomas J.; Chaturvedi, Vishnu; Espinel-Ingroff, Ana; Ghannoum, Mahmoud A.; Gosey, Linda L.; Odds, Frank C.; Rinaldi, Michael G.; Sheehan, Daniel J.; Warnock, David W.

    2001-01-01

    Development of standardized antifungal susceptibility testing methods has been the focus of intensive research for the last 15 years. Reference methods for yeasts (NCCLS M27-A) and molds (M38-P) are now available. The development of these methods provides researchers not only with standardized methods for testing but also with an understanding of the variables that affect interlaboratory reproducibility. With this knowledge, we have now moved into the phase of (i) demonstrating the clinical value (or lack thereof) of standardized methods, (ii) developing modifications to these reference methods that address specific problems, and (iii) developing reliable commercial test kits. Clinically relevant testing is now available for selected fungi and drugs: Candida spp. against fluconazole, itraconazole, flucytosine, and (perhaps) amphotericin B; Cryptococcus neoformans against (perhaps) fluconazole and amphotericin B; and Aspergillus spp. against (perhaps) itraconazole. Expanding the range of useful testing procedures is the current focus of research in this area. PMID:11585779

  4. [Chalcones and their heterocyclic analogs as potential antifungal chemotherapeutic agents].

    PubMed

    Opletalová, V; Sedivý, D

    1999-11-01

    Chalcones and their heterocyclic analogues show various biological effects, e.g. anti-inflammatory, antitumour, antibacterial, antituberculous, antiviral, antiprotozoal, gastroprotective, and others. The present review discusses in greater detail the fungistatic and fungicide properties of these compounds and presents also their chemical structures. The mechanism of antifungal effects of chalcones and their analogues has not been investigated in greater detail. Due to the presence of a reactive ketovinyl moiety in the molecule the compounds of this type are able to react with the thiol groups of enzymes. It cannot be excluded that chalcones interfere with the normal function of the membranes of fungi and moulds. Further investigation of chemical, physical, and biological properties of chalcones and their analogues could lead to the elucidation of the mechanism of their action and finding of effective fungicidal and fungistatic agents in this group of organic substances. PMID:10748740

  5. Medical claims and current applications of the potent echinocandin antifungals.

    PubMed

    Smith, Leif; Lu, Shi-En

    2010-01-01

    Echinocandins are an interesting group of antifungals that were originally discovered in the early 1970s. They are a group of lipopeptides produced by fungi which consists of a large number of structural analogs of echinocandin B, the first echinocandin to be structurally characterized. All clinically used echinocandins are produced semi-synthetically. The cyclic peptide nuclear core is retained while the acyl chain is replaced to minimize toxicity and expand their spectrum of activity. It was not until 2002 with the introduction of caspofungin (Cancidas) into the clinics that their true worth was realized. Since the introduction of caspofungin, two other echinocandins, micafungin (Mycamine) and anidulafungin (Eraxis) have been introduced. They all function by inhibiting an enzyme unique for fungal cell wall production, which presumably accounts for their minimal side-effects. In this review, topics pertaining to their production, structural diversity, and use in the clinic along with the recent patents are discussed. PMID:19929842

  6. Cytotoxic and Antifungal Activities of Diverse α-Naphthylamine Derivatives

    PubMed Central

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

    2012-01-01

    Diverse α-naphthylamine derivatives were easily prepared from corresponding aldimines derived from commercially available α-naphthaldehyde and anilines or isomeric pyridinecarboxyaldehydes and α-naphthylamine. The secondary amines obtained were tested as possible antifungal and cytotoxic agents. The diverse N-aryl-N-[1-(1-naphthyl)but-3-enyl]amines obtained were active (IC50 < 10 μg/mL) against breast (MCF-7), non-small cell lung (H-460), and central nervous system (SF-268) human cancer cell lines, while N-(pyridinylmethyl)-naphthalen-1-amines resulted in activity against (MIC 25–32 μg/mL) some human opportunistic pathogenic fungi including yeasts, hialohyphomycetes, and dermatophytes. PMID:23264936

  7. [MIKAMINOM ANTIFUNGAL THERAPY IN NEWBORNS AND INFANTS WITH SURGICAL PATHOLOGY].

    PubMed

    Melnikova, N I; Strogonov, I A; Kartseva, E V; Haritonova, G D; Gliznutsin, O E; Gabulaev, S V; Pulikova, E M

    2016-01-01

    Prolonged empiric and etiotropic therapy of multidrug-resistant or pan-resistant bacterial flora in different gestation age newborns has led to the growth of resistant fungalflora in intencive care units (ICU). According to risk factors and rating scales every child of ICU undergoing the abdominal cavity surgery is threatened the development of a fungal infection and requires antifungal therapy appointment or causal prophylactic. In recent years, before the advent of medications of the group of echinocandins, therapy of invasive fungal infections has been a challenge. Currently alternative drug to diflucane in neonates and infants is micafungine (mycamine) in the dose of 2-8 mg/kg/day, depending on the signs of infestation and severity of the condition. PMID:27192854

  8. Synthesis and antifungal activity of bile acid-derived oxazoles.

    PubMed

    Fernández, Lucía R; Svetaz, Laura; Butassi, Estefanía; Zacchino, Susana A; Palermo, Jorge A; Sánchez, Marianela

    2016-04-01

    Peracetylated bile acids (1a-g) were used as starting materials for the preparation of fourteen new derivatives bearing an oxazole moiety in their side chain (6a-g, 8a-g). The key step for the synthetic path was a Dakin-West reaction followed by a Robinson-Gabriel cyclodehydration. A simpler model oxazole (12) was also synthesized. The antifungal activity of the new compounds (6a-g) as well as their starting bile acids (1a-g) was tested against Candida albicans. Compounds 6e and 6g showed the highest percentages of inhibition (63.84% and 61.40% at 250 μg/mL respectively). Deacetylation of compounds 6a-g, led to compounds 8a-g which showed lower activities than the acetylated derivatives. PMID:26827629

  9. Characterization of Chitosan Nanofiber Sheets for Antifungal Application

    PubMed Central

    Egusa, Mayumi; Iwamoto, Ryo; Izawa, Hironori; Morimoto, Minoru; Saimoto, Hiroyuki; Kaminaka, Hironori; Ifuku, Shinsuke

    2015-01-01

    Chitosan produced by the deacetylation of chitin is a cationic polymer with antimicrobial properties. In this study, we demonstrate the improvement of chitosan properties by nanofibrillation. Nanofiber sheets were prepared from nanofibrillated chitosan under neutral conditions. The Young’s modulus and tensile strength of the chitosan NF sheets were higher than those of the chitosan sheets prepared from dissolving chitosan in acetic acid. The chitosan NF sheets showed strong mycelial growth inhibition against dermatophytes Microsporum and Trichophyton. Moreover, the chitosan NF sheets exhibited resistance to degradation by the fungi, suggesting potentials long-lasting usage. In addition, surface-deacetylated chitin nanofiber (SDCNF) sheets were prepared. The SDCNF sheet had a high Young’s modulus and tensile strength and showed antifungal activity to dermatophytes. These data indicate that nanofibrillation improved the properties of chitosan. Thus, chitosan NF and SDCNF sheets are useful candidates for antimicrobial materials. PMID:26540046

  10. Antifungal and cytotoxic activity of withanolides from Acnistus arborescens.

    PubMed

    Roumy, Vincent; Biabiany, Murielle; Hennebelle, Thierry; Aliouat, El Moukhtar; Pottier, Muriel; Joseph, Henry; Joha, Sami; Quesnel, Bruno; Alkhatib, Racha; Sahpaz, Sevser; Bailleul, François

    2010-07-23

    Three compounds were isolated from Acnistus arborescens, a tree commonly used in South and Central America in traditional medicine against several infectious diseases, some of which are caused by fungi. Bioassay-guided fractionation of a MeOH extract of leaves, based on its anti-Pneumocystis carinii activity, led to the isolation of compounds 1-3. Mono- and bidimensional NMR analyses enabled identification of two new withanolides, (20R,22R)-5beta,6beta-epoxy-4beta,12beta,20-trihydroxy-1-oxowith-2-en-24-enolide (1) and (20R,22R)-16beta-acetoxy-3beta,4beta;5beta,6beta-diepoxy-12beta,20-dihydroxy-1-oxowith-24-enolide (2), and withanolide D (3). Antifungal activity on 13 fungi responsible for human infections (five dermatophytes, one nondermatophyte mold, six yeasts, and Pneumocystis carinii) was examined. Cytotoxicity of these compounds was also evaluated in vitro. PMID:20590148

  11. Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity

    PubMed Central

    Khedr, Mohammed A

    2015-01-01

    Fungal infections are a main reason for the high mortality rate worldwide. It is a challenge to design selective antifungal agents with broad-spectrum activity. Lanosterol 14α-demethylase is an attractive target in the design of antifungal agents. Seven compounds were selected from a number of designed compounds using a rational docking study. These compounds were synthesized and evaluated for their antifungal activity. In silico study results showed the high binding affinity to lanosterol 14α-demethylase (−24.49 and −25.83 kcal/mol) for compounds V and VII, respectively; these values were greater than those for miconazole (−18.19 kcal/mol) and fluconazole (−16.08 kcal/mol). Compound V emerged as the most potent antifungal agent among all compounds with a half maximal inhibitory concentration of 7.01, 7.59, 7.25, 31.6, and 41.6 µg/mL against Candida albicans, Candida parapsilosis, Aspergillus niger, Trichophyton rubrum, and Trichophyton mentagrophytes, respectively. The antifungal activity for most of the synthesized compounds was more potent than that of miconazole and fluconazole. PMID:26309398

  12. A Comparative Study of Antifungal Activity of Endodontic Irrigants

    PubMed Central

    Mohammadi, Zahed; Asgary, Saeed

    2015-01-01

    Introduction: The purpose of this in vitro study was to assess the antifungal activity of final canal rinse with either three concentrations of sodium hypochlorite (NaOCl) (0.5, 2.6 and 6%), two concentrations of chlorhexidine (CHX) (2% and 0.2%), MTAD, Tetraclean, Hypoclean and Chlor-Xtra on Candida albicans (C. albicans) in a human tooth model. Methods and Materials: Two hundred and thirty five extracted human maxillary central and lateral incisors were used in this study. Teeth were randomly divided into nine test groups (n=25) and positive and a negative control groups (n=5). After cleaning and shaping, teeth were contaminated with C. albicans and incubated for 72 h. The irrigation solution in nine experimental groups included: 6% NaOCl, 2.6% NaOCl, 0.5% NaOCl, 2% CHX, 0.2% CHX, MTAD, Tetraclean, Hypoclean and Chlor-Xtra. After culturing on Sabouraud 4% dextrose agar, colony-forming units (CFU) were counted. Results: 6% NaOCl, 2% CHX and Chlor-Xtra were equally effective (P>0.05) and significantly superior to MTAD and Tetraclean (P<0.05). In addition, the effectiveness of Tetraclean and MTAD was significantly less than Hypoclean, NaOCl at all concentrations (6% 2.6% and 0.5%), MTAD and 0.2% CHX (P<0.05). Furthermore, Tetraclean was significantly more effective than MTAD (P<0.05). Conclusion: Antifungal activity of 6% NaOCl, Chlor-Xtra and 2% CHX was significantly greater than 2.6% NaOCl, 0.5% NaOCl, MTAD, 0.2% CHX and Tetraclean. PMID:25834602

  13. Which antifungal agent for onychomycosis? A pharmacoeconomic analysis.

    PubMed

    Joish, V N; Armstrong, E P

    2001-01-01

    The incidence of fungal nail infections is increasing and this is possibly because of several factors: better methods of detection, a growing population of immunocompromised patients who have a greater susceptibility to such infections, the increased use of immunosuppressive drugs, the increasing number of elderly people, worldwide travel, and the use of communal bathing facilities. Onychomycosis is a fungal infection of the fingernails and toenails that accounts for about 30% of all superficial fungal infections. It is characterised by nail discoloration, thickening and ultimately destruction of the nail plate. Management of this disease has improved significantly and treatment patterns have dramatically changed in recent years as a result of advances in new treatment options (e.g. oral antifungal agents) and changes in treatment regimens (e.g. pulse therapy). Also, newer drugs for onychomycosis have improved tolerability profiles compared with older agents. The overall costs of treating onychomycosis are substantial, and it has been estimated that direct cost for US Medicare patients with the disease is 43 million US dollars per year (year of costing not available). Pharmacoeconomic studies help in the decision-making process when selecting the most cost-effective antifungal agents to treat onychomycosis. To date there have been a number of national and international economic studies aimed at effectively assessing the efficacy and costs of the treatment options available to cure onychomycosis. The objectives of this paper are to (i) review the published findings regarding the epidemiology of onychomycosis; (ii) summarise the original pharmacoeconomic studies that describe the economic impact of the disease; and (iii) address the impact of the disease on patients' health-related quality of life. PMID:11735669

  14. In vitro antifungal susceptibility of Malassezia furfur from bloodstream infections.

    PubMed

    Iatta, Roberta; Figueredo, Luciana A; Montagna, Maria Teresa; Otranto, Domenico; Cafarchia, Claudia

    2014-11-01

    Fungaemia caused by Malassezia spp. in hospitalized patients requires prompt and appropriate therapy, but standard methods for the definition of the in vitro antifungal susceptibility have not been established yet. In this study, the in vitro susceptibility of Malassezia furfur from bloodstream infections (BSIs) to amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), posaconazole (POS) and voriconazole (VRC) was assessed using the broth microdilution (BMD) method of the Clinical and Laboratory Standards Institute (CLSI) with different media such as modified Sabouraud dextrose broth (SDB), RPMI and Christensen's urea broth (CUB). Optimal broth media that allow sufficient growth of M. furfur, and produce reliable and reproducible MICs using the CLSI BMD protocol were assessed. Thirty-six M. furfur isolates collected from BSIs of patients before and during AMB therapy, and receiving FLC prophylaxis, were tested. A good growth of M. furfur was observed in RPMI, CUB and SDB at 32 °C for 48 and 72 h. No statistically significant differences were detected between the MIC values registered after 48 and 72 h incubation. ITC, POS and VRC displayed lower MICs than FLC and AMB. These last two antifungal drugs showed higher and lower MICs, respectively, when the isolates were tested in SDB. SDB is the only medium in which it is possible to detect isolates with high FLC MICs in patients receiving FLC prophylaxis. A large number of isolates showed high AMB MIC values regardless of the media used. In conclusion, SDB might be suitable to determine triazole susceptibility. However, the media, the drug formulation or the breakpoints herein applied might not be useful for assessing the AMB susceptibility of M. furfur from BSIs. PMID:25168965

  15. Antifungal agents for onychomycosis: new treatment strategies to improve safety.

    PubMed

    Zane, Lee T; Chanda, Sanjay; Coronado, Dina; Del Rosso, James

    2016-01-01

    Onychomycosis is a common and difficult-to-treat fungal infection of the nail unit that gradually leads to dystrophic changes of the nail plate and nail bed. If untreated, infection progresses and may lead to discomfort, reduced quality of life, and risk of complications in patients with comorbid conditions (eg, diabetes, human immunodeficiency virus, peripheral vascular disease). Onychomycosis treatments are designed to eradicate causative pathogens (most commonly Trichophyton rubrum and Trichophyton mentagrophytes), restore healthy nails, and prevent recurrence or spread of infection. Given the deep-seated nature of most cases of onychomycosis, an effective antifungal agent needs to achieve and maintain sufficient drug concentrations throughout the nail unit for the duration of healthy nail in-growth. Oral antifungal drugs are the most effective available therapy and are generally well tolerated, but may be limited by safety concerns and the potential for drug-drug interactions (DDIs). Thus, treating physicians and pharmacists must be cognizant of a patient's current medications; indeed, it may not be feasible to treat onychomycosis in patients with diabetes, heart disease, or depression because of the risk for DDIs. Current topical therapy is not associated with risk of DDIs. Tavaborole and efinaconazole, two recently approved topical agents, have demonstrated good nail penetration and high negative culture rates in clinical trials of patients with onychomycosis. This article provides the treating physician and pharmacist with information on the safety and effectiveness of current oral (allylamine, azole) and topical (ciclopirox, efinaconazole, tavaborole) treatment to aid in making informed treatment decisions based on the unique characteristics (medication history, comorbidities, nature of onychomycosis) of each patient. PMID:27136621

  16. Antifungal Properties of Haem Peroxidase from Acorus calamus

    PubMed Central

    GHOSH, MODHUMITA

    2006-01-01

    • Background and Aims Plants have evolved a number of inducible defence mechanisms against pathogen attack, including synthesis of pathogenesis-related proteins. The aim of the study was to purify and characterize antifungal protein from leaves of Acorus calamus. • Methods Leaf proteins from A. calamus were fractionated by cation exchange chromatography and gel filtration and the fraction inhibiting the hyphal extension of phytopathogens was characterized. The temperature stability and pH optima of the protein were determined and its presence was localized in the leaf tissues. • Key Results The purified protein was identified as a class III haem peroxidase with a molecular weight of approx. 32 kDa and pI of 7·93. The temperature stability of the enzyme was observed from 5 °C to 60 °C with a temperature optimum of 36 °C. Maximum enzyme activity was registered at pH 5·5. The pH and temperature optima were corroborated with the antifungal activity of the enzyme. The enzyme was localized in the leaf epidermal cells and lumen tissues of xylem, characteristic of class III peroxidases. The toxic nature of the enzyme which inhibited hyphal growth was demonstrated against phytopathogens such as Macrophomina phaseolina, Fusarium moniliforme and Trichosporium vesiculosum. Microscopic observations revealed distortion in the hyphal structure with stunted growth, increased volume and extensive hyphal branching. • Conclusions This study indicates that peroxidases may have a role to play in host defence by inhibiting the hyphal extension of invading pathogens. PMID:17056613

  17. Antifungal Effect of Plant Essential Oils on Controlling Phytophthora Species

    PubMed Central

    Amini, Jahanshir; Farhang, Vahid; Javadi, Taimoor; Nazemi, Javad

    2016-01-01

    In this study, antifungal activity of essential oils of Cymbopogon citratus and Ocimum basilicum and two fungicides Mancozeb and Metalaxyl-Mancozeb in six different concentrations were investigated for controlling three species of Phytophthora, including P. capsici, P. drechsleri and P. melonis on pepper, cucumber and melon under in vitro and greenhouse conditions, respectively. Under the in vitro condition, the median effective concen- tration (EC50) values (ppm) of plant essential oils and fungicides were measured. In greenhouse, soil infested with Phytophthora species was treated by adding 50 ml of essential oils and fungicides (100 ppm). Disease severity was determined after 28 days. Among two tested plant essential oils, C. citratus had the lowest EC50 values for inhibition of the mycelial growth of P. capsici (31.473), P. melonis (33.097) and P. drechsleri (69.112), respectively. The mean EC50 values for Metalaxyl-Mancozeb on these pathogens were 20.87, 20.06 and 17.70, respectively. Chemical analysis of plant essential oils by GC-MS showed that, among 42 compounds identified from C. citratus, two compounds β-geranial (α-citral) (39.16%) and z-citral (30.95%) were the most abundant. Under the greenhouse condition, Metalaxyl-Mancozeb caused the greatest reduction in disease severity, 84.2%, 86.8% and 92.1% on melon, cucumber, and pepper, respectively. The C. citratus essential oil reduced disease severity from 47.4% to 60.5% compared to the untreated control (p≤0.05). Essential oils of O. basilicum had the lowest effects on the pathogens under in vitro and greenhouse conditions. These results show that essential oils may contribute to the development of new antifungal agents to protect the crops from Phytophthora diseases. PMID:26889111

  18. Antifungal Effect of Plant Essential Oils on Controlling Phytophthora Species.

    PubMed

    Amini, Jahanshir; Farhang, Vahid; Javadi, Taimoor; Nazemi, Javad

    2016-02-01

    In this study, antifungal activity of essential oils of Cymbopogon citratus and Ocimum basilicum and two fungicides Mancozeb and Metalaxyl-Mancozeb in six different concentrations were investigated for controlling three species of Phytophthora, including P. capsici, P. drechsleri and P. melonis on pepper, cucumber and melon under in vitro and greenhouse conditions, respectively. Under the in vitro condition, the median effective concen- tration (EC50) values (ppm) of plant essential oils and fungicides were measured. In greenhouse, soil infested with Phytophthora species was treated by adding 50 ml of essential oils and fungicides (100 ppm). Disease severity was determined after 28 days. Among two tested plant essential oils, C. citratus had the lowest EC50 values for inhibition of the mycelial growth of P. capsici (31.473), P. melonis (33.097) and P. drechsleri (69.112), respectively. The mean EC50 values for Metalaxyl-Mancozeb on these pathogens were 20.87, 20.06 and 17.70, respectively. Chemical analysis of plant essential oils by GC-MS showed that, among 42 compounds identified from C. citratus, two compounds β-geranial (α-citral) (39.16%) and z-citral (30.95%) were the most abundant. Under the greenhouse condition, Metalaxyl-Mancozeb caused the greatest reduction in disease severity, 84.2%, 86.8% and 92.1% on melon, cucumber, and pepper, respectively. The C. citratus essential oil reduced disease severity from 47.4% to 60.5% compared to the untreated control (p≤0.05). Essential oils of O. basilicum had the lowest effects on the pathogens under in vitro and greenhouse conditions. These results show that essential oils may contribute to the development of new antifungal agents to protect the crops from Phytophthora diseases. PMID:26889111

  19. Antibacterial, Antifungal and antioxidant activities of some medicinal plants.

    PubMed

    Wazir, Asma; Mehjabeen, -; Jahan, Noor; Sherwani, Sikander Khan; Ahmad, Mansoor

    2014-11-01

    The purpose of this study was to evaluate the antibacterial, antifungal and antioxidant activities of medicinal plants. The antibacterial activity of methanolic extracts of three medicinal plants (Swertia chirata, Terminalia bellerica and Zanthoxylum armatum) were tested against Gentamicin (standard drug) on eleven gram positive and seventeen gram negative bacteria by agar well method. It was revealed that seven-gram negative and six gram positive bacterial species were inhibited by these plant extracts. Minimum inhibitory concentrations (MIC) of the extracts were determined by broth micro-dilution method. The significant MIC value of Swertia chirata was 20mg/ml against Serratia marcesens, Zanthoxylum armatum was 10 mg/ml against Aeromonas hydrophila and Terminali bellerica was 20mg/ml against Acinetobacter baumanii as well as Serratia marcesens. Antifungal screening was done for methanolic extracts of these plants by agar well method with the 6 saprophytic, 5 dermatophytic and 6 yeasts. In this case Griseofulvin was used as a standard. All saprophytes and dermatophytes were showed resistance by these plants extracts except Microsporum canis, which was inhibited by Z. armatum and S. chirata extracts. The significant MIC value of Zanthoxylum armatum was 10mg/ml against Microsporum canis and Swertia chirata was 10mg/ml against Candida tropicalis. The anti-oxidant study was performed by DPPH free radical scavenging assay using ascorbic acid as a reference standard. Significant antioxidant activities were observed by Swertia chirata and Zanthoxylum armatum at concentration 200μg/ml was 70% DPPH scavenging activity (EC50=937.5μg/ml) while Terminalia bellerica showed 55.6% DPPH scavenging activity (EC50=100μg/ml). This study has shown that these plants could provide potent antibacterial compounds and may possible preventive agents in ROS related ailments. PMID:26045377

  20. Structure-based rational design, synthesis and antifungal activity of oxime-containing azole derivatives.

    PubMed

    Xu, Yulan; Sheng, Chunquan; Wang, Wenya; Che, Xiaoying; Cao, Yongbing; Dong, Guoqiang; Wang, Shengzheng; Ji, Haitao; Miao, Zhenyuan; Yao, Jianzhong; Zhang, Wannian

    2010-05-01

    In an attempt to find novel azole antifungal agents with improved activity and broader spectrum, computer modeling was used to design a series of new azoles with piperidin-4-one O-substituted oxime side chains. Molecular docking studies revealed that they formed hydrophobic and hydrogen-bonding interactions with lanosterol 14alpha-demethylase of Candida albicans (CACYP51). In vitro antifungal assay indicates that most of the synthesized compounds showed good activity against tested fungal pathogens. In comparison with fluconazole, itraconazole and voriconazole, several compounds (such as 10c, 10e, and 10i) show more potent antifungal activity and broader spectrum, suggesting that they are promising leads for the development of novel antifungal agents. PMID:20362444

  1. Mode of Action for Reproductive and Hepatic Toxicity Inferred from a Genomic Study of Triazole Antifungals

    EPA Science Inventory

    The mode of action for the reproductive toxicity of triazole antifungals have been previously characterized by an observed increased in serum testosterone, hepatotoxicity, and reduced insemination and fertility indices. In order to refine our mechanistic understanding of these m...

  2. Antifungal Imidazole-Decorated Cationic Amphiphiles with Markedly Low Hemolytic Activity.

    PubMed

    Benhamou, Raphael I; Steinbuch, Kfir B; Fridman, Micha

    2016-08-01

    Herein we report that an imidazole-decorated cationic amphiphile derived from the pseudo-disaccharide nebramine has potent antifungal activity against strains of Candida glabrata pathogens. In combination with the natural bis-benzylisoquinoline alkaloid tetrandrine the reported antifungal cationic amphiphile demonstrated synergistic antifungal activity against Candida albicans pathogens. This unique membrane disruptor caused no detectible mammalian red blood cell hemolysis at concentrations up to more than two orders of magnitude greater than its minimal inhibitory concentrations against the tested C. glabrata strains. We provide evidence that potency against C. glabrata may be associated with differences between the drug efflux pumps of C. albicans and C. glabrata. Imidazole decorated-cationic amphiphiles show promise for the development of less toxic membrane-disrupting antifungal drugs and drug combinations. PMID:27258738

  3. Novel hybrids of fluconazole and furanones: design, synthesis and antifungal activity.

    PubMed

    Borate, Hanumant B; Sawargave, Sangmeshwer P; Chavan, Subhash P; Chandavarkar, Mohan A; Iyer, Ramki; Tawte, Amit; Rao, Deepali; Deore, Jaydeep V; Kudale, Ananada S; Mahajan, Pankaj S; Kangire, Gopinath S

    2011-08-15

    During our efforts to develop new antifungal agents, a number of hybrid molecules containing furanones and fluconazole pharmacophores were designed and synthesized. The new chemical entities thus synthesized were tested for their potential as antifungal agents against various fungal strains and it was observed that the compounds with general structure 7 were potent inhibitors of Candida albicans ATCC 24433, Candida glabrata ATCC 90030, Candida tropicalis ATCC 750 and Candida neoformans ATCC 34664 while the fluconazole analogues 12 exhibited antifungal activity against Candida albicans ATCC 24433 and Candida glabrata ATCC 90030. The structure-activity relationship for these compounds is discussed. The synthetic strategies used in the present work have potential to prepare a large number of compounds for further refinement of structures to obtain molecules suitable for development as antifungal drugs. PMID:21757344

  4. Self-assembled cardanol azo derivatives as antifungal agent with chitin-binding ability.

    PubMed

    Mahata, Denial; Mandal, Santi M; Bharti, Rashmi; Gupta, Vinay Krishna; Mandal, Mahitosh; Nag, Ahindra; Nando, Golok B

    2014-08-01

    Cardanol is a non-isoprenoic phenolic lipid-mixture of distilled cashew nut shell liquid obtained from Anacardium occidentale. Herein, cardanol is purified from cashew nut shell liquid (CNSL) and synthesized to new compounds with different azo amphiphiles. These synthesized compounds are allowed to self-assembled in hydrophobic environment and checked antifungal activity against Candida albicans. Self-assembled structure of CABA showed higher antifungal activity (16μg/mL) and chitin-binding ability in comparison to CAP and CANB. Furthermore, the self-assembled azo amphiphiles are immobilized with silver ions to prepare hydrogel which showed eight folds enhanced antifungal activity. Toxicity is reduced by several folds of self-assembled or hydrogel structure in comparison to pure compounds. Thus, the self-assembled structure of amphiphiles and their hydrogels have been found to be new macromolecules of interest with potential use as antifungal drugs. PMID:24836571

  5. Study on Mutagenic Breeding of Bacillus Subtilis and Properties of Its Antifungal Substances

    NASA Astrophysics Data System (ADS)

    Liu, Jing; Yao, Jianming

    2004-08-01

    Bacillus subtitles JA isolated by our laboratory produced a large amount of antifungal substances, which had strong inhibitory activity against various plant pathogenic fungi, such as Rhizoctonia solani, Fusarium graminearum and so on. Ion beam implantation as a new mutagenic methods was applied in our studay. After B. subtitles JA was implanted by N+ ions, a strain designated as B. subtitles JA-026 was screened and obtained, which had a higher ability to produce those antifungal substances. A series of experiments indicated that the antifungal substances were thermostable and partially sensitive to proteinases K and tryproteinase. When the fermentating broth was fractionated with ammonium sulphate of a final saturation of 70%, the precipitate-enhanced inhibitory activity while the supernatant lost this activity. It appeared that the antifungal substances were likely to be protein.

  6. Purification and Identification of Two Antifungal Cyclic Peptides Produced by Bacillus amyloliquefaciens L-H15.

    PubMed

    Han, Yuzhu; Zhang, Bao; Shen, Qian; You, Chengzhen; Yu, Yaqiong; Li, Pinglan; Shang, Qingmao

    2015-08-01

    Bacillus amyloliquefaciens L-H15 with broad spectrum antifungal activity was used as a biocontrol agent to suppress Fusarium oxysporum and other soil-borne fungal plant pathogens. Two antifungal fractions were isolated by bioactivity-guided reversed-phase high-performance liquid chromatography. The two compounds were identified by tandem Q-TOF mass spectroscopy as C15 Iturin A (1) and a novel cyclic peptide with a molecular weight of 852.4 Da (2). Both compounds showed good inhibitory activities against three plant fungal pathogens in cylinder-plate diffusion assay. To our best knowledge, this is the first report on a cyclic antifungal peptide with a molecular weight of 852.4 Da. The strong antifungal activity suggests that the B. amyloliquefaciens L-H15 and its bioactive components might provide an alternative resource for the biocontrol of plant diseases and sustainable agriculture. PMID:26123083

  7. Synthesis and antifungal activity evaluation of new heterocycle containing amide derivatives.

    PubMed

    Wang, Xuesong; Gao, Sumei; Yang, Jian; Gao, Yang; Wang, Ling; Tang, Xiaorong

    2016-01-01

    A series of heterocycle containing amide derivatives (1-28) were synthesised by the combination of acyl chlorides (1a, 2a) and heterocyclic/homocyclic ring containing amines, and their in vitro antifungal activity was evaluated against five plant pathogenic fungi, namely Gibberella zeae, Helminthosporium maydis, Rhizoctonia solani, Botrytis cinerea and Sclerotinia sclerotiorum. Results of antifungal activity analysis indicated that some of the products showed good to excellent antifungal activity, as compound 2 showed excellent activity against G. zeae and R. solani and potent activity against H. maydi, B. cinerea and S. sclerotiorum, and compounds 1, 8 and 10 also displayed excellent antifungal potential against H. maydi, B. cinerea and S. sclerotiorum and good activity against R. solani when compared with the standard carbendazim. PMID:26140452

  8. Antifungal activity upon Saccharomyces cerevisiae of iturin A, mycosubtilin, bacillomycin L and of their derivatives; inhibition of this antifungal activity by lipid antagonists.

    PubMed

    Besson, F; Peypoux, F; Michel, G; Delcambe, L

    1979-08-01

    The antifungal activity of three antibiotics of the iturin group: iturin A, mycosubtilin, bacillomycin L and of eleven methylated and acetylated derivatives of these antibiotics was tested upon Saccharomyces cerevisiae. The lowest MIC values were found for natural antibiotics. The substitution of polar groups diminished the antifungal activity. Various lipids, sterols, fatty acids, fatty acid methyl esters and phospholipids were tested as inhibitors of the antifungal activity of iturin A, mycosubtilin and bacillomycin L. Cholesterol was the strongest inhibitor upon the three antibiotics; ergosterol, oleic acid and cis-vaccenic acid were less potent inhibitors. Among phospholipids, phosphatidyl choline inhibited bacillomycin L and iturin A while diphosphatidyl glycerol inhibited bacillomycin L and mycosubtilin. The inhibitory effect appeared to be dependent on the nature of both the hydrophilic group and the fatty acid part of phospholipids. PMID:387691

  9. The role of antifungal and antiviral agents in primary dental care.

    PubMed

    Lewis, Mike

    2014-11-01

    In comparison to the range of antibiotics used in medicine, the spectrum of antifungal and antiviral drugs used in primary dental care is relatively limited. In practical terms, there are only three antifungal agents and two antiviral agents that have a role. This paper will describe the clinical presentation of orofacial candidal and viral infections and the use of antimicrobial drugs in their management. PMID:25668378

  10. In Vitro Antifungal Activity of Kampo Medicine Water Extracts against Trichophyton rubrum.

    PubMed

    Da, Xia; Takahashi, Hitoshi; Hein, Kyaw Zaw; Morita, Eishin

    2016-06-01

    Kampo medicines consist of a variety of crude animal, plant, and mineral extracts that have long been used to relieve different symptoms, and are relatively safe. However, their mechanisms of actions have not been well investigated. We screened 61 commercially available Kampo medicines to determine if they contain constituents with antifungal activity against Trichophyton rubrum. The antifungal effect of the Kampo medicines was determined by measuring the mean absorbance of treated fungal culture media. Lower absorbance values suggested a higher inhibition of the growth rate of T. rubrum by the Kampo medicines. We found that seven of the evaluated formulations exhibited a comparable antifungal activity to that of fluconazole at 14 mg/mL. The seven active Kampo medicines were Saiko-keishi-kankyou-to, Saiko-ka-ryukotsu-borei-to, Saiko-keishi-to, Keishi-ka-ryukotsu-borei-to, Dai-saiko-to, Bohu-tsu-sho-san, and Otsu-ji-to. The seven Kampo medicines with antifungal activity contain 30 different crude extracts, and Ou-gon (Scutellaria root) is a supplement contained in six of the seven formulations. Therefore, Ou-gon was considered to play a major role in their antifungal effect. The antifungal assay of the Ou-gon water extract showed that it significantly inhibited the growth of T. rubrum at a concentration of 20 mg/mL. Future studies will focus on the isolation and identification of the antifungal components of the crude extracts of Ou-gon, which may be potentially useful, new, and safe antifungal drugs. PMID:27534111

  11. Role of Antifungal Susceptibility Testing in Non-Aspergillus Invasive Mold Infections.

    PubMed

    Lamoth, Frédéric; Damonti, Lauro; Alexander, Barbara D

    2016-06-01

    No clinical breakpoints are available to delineate antifungal drug efficacy in non-Aspergillus invasive mold infections (NAIMIs). In this analysis of 39 NAIMI episodes, the MIC of the first-line antifungal drug was the most important predictor of therapeutic response. For amphotericin B, an MIC of ≤0.5 μg/ml was significantly associated with better 6-week outcomes. PMID:27008871

  12. Characterization of Tamoxifen as an Antifungal Agent Using the Yeast Schizosaccharomyces Pombe Model Organism.

    PubMed

    Zhang, Xibo; Fang, Yue; Jaiseng, Wurentuya; Hu, Lingling; Lu, Yabin; Ma, Yan; Furuyashiki, Tomoyuki

    2015-01-01

    Tamoxifen, a selective estrogen receptor modulator used for managing breast cancer, is known to have antifungal activity. However, its molecular mechanism remains unknown. Using the fission yeast Schizosaccharomyces pombe as a model organism, we have explored the mechanism involved in antifungal action of tamoxifen. Since tamoxifen was shown to inhibit the binding of calmodulin to calcineurin in fungi, we first examined involvement of these molecules and found that overexpression of a catalytic subunit of calcineurin and its constitutively active mutant as well as calmodulin increases tamoxifen sensitivity. Since terbinafine and azoles inhibit enzymes for ergosterol biosynthesis, Erg1 and Erg11, for their antifungal actions, we also examined involvement of these molecules. Overexpression of Erg1 and Erg11 reduced the sensitivity to terbinafine and azoles, respectively, but increased tamoxifen sensitivity, suggesting that ergosterol biosynthesis is differently related to the action of tamoxifen and those of terbinafine and azoles. To elucidate molecules involved in tamoxifen action, we performed a genome-wide screen for altered sensitivity to tamoxifen using a fission yeast gene deletion library, and identified various hypersensitive and resistant mutants to this drug. Notably, these mutants are rarely overlapped with those identified in similar genetic screens with currently used antifungals, suggesting a novel mode of antifungal action. Furthermore, tamoxifen augmented antifungal actions of terbinafine and azoles, suggesting synergetic actions between these drugs. Therefore, our findings suggest that calmodulin-calcineurin pathway and ergosterol biosynthesis are related to antifungal action of tamoxifen, and propose novel targets for antifungal development as well as combined therapy with tamoxifen for fungal diseases. PMID:26628015

  13. Antifungal chalcones and new caffeic acid esters from Zuccagnia punctata acting against soybean infecting fungi.

    PubMed

    Svetaz, Laura; Tapia, Alejandro; López, Silvia N; Furlán, Ricardo L E; Petenatti, Elisa; Pioli, Rosanna; Schmeda-Hirschmann, Guillermo; Zacchino, Susana A

    2004-06-01

    The crude methanolic extract of Zuccagnia punctata was active toward the fungal pathogens of soybean Phomopsis longicolla and Colletotrichum truncatum. Assay guided fractionation led to the isolation of two chalcones, one flavanone and a new caffeoyl ester derivative as the compounds responsible for the antifungal activity. Another new caffeoyl ester derivative was isolated from the antifungal chloroform extract but proved to be inactive against the soybean infecting fungi up to 50 microg/mL PMID:15161186

  14. Synthesis and antifungal activity of novel triazole compounds containing piperazine moiety.

    PubMed

    Wang, Yanwei; Xu, Kehan; Bai, Guojing; Huang, Lei; Wu, Qiuye; Pan, Weihua; Yu, Shichong

    2014-01-01

    Design and synthesis of triazole library antifungal agents having piperazine side chains, analogues to fluconazole were documented. The synthesis highlighted utilization of the click chemistry on the basis of the active site of the cytochrome P450 14α-demethylase (CYP51). Their structures were characterized by (1)H-NMR, (13)C-NMR, MS and IR. The influences of piperazine moiety on in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi. PMID:25090121

  15. Hyalodendrosides A and B, antifungal triterpenoid glycosides from a lignicolous hyphomycete, Hyalodendron species.

    PubMed

    Bills, G; Dombrowski, A; Morris, S A; Hensens, O; Liesch, J M; Zink, D L; Onishi, J; Meinz, M S; Rosenbach, M; Thompson, J R; Schwartz, R E

    2000-01-01

    Two antifungal triterpenoid glycosides, hyalodendrosides A and B (1 and 2), were isolated from a solid matrix fermentation of a lignicolous hyphomycete, Hyalodendron sp. Their structures were determined based upon extensive examination of spectral parameters, particularly NMR and MS data. Both compounds have beta-linked glucose moieties. Compounds 1 and 2 show weak to moderate antifungal activity against some clinically relevant fungi. PMID:10650085

  16. Candida tropicalis Antifungal Cross-Resistance Is Related to Different Azole Target (Erg11p) Modifications

    PubMed Central

    Forastiero, A.; Mesa-Arango, A. C.; Alastruey-Izquierdo, A.; Alcazar-Fuoli, L.; Bernal-Martinez, L.; Pelaez, T.; Lopez, J. F.; Grimalt, J. O.; Gomez-Lopez, A.; Cuesta, I.; Zaragoza, O.

    2013-01-01

    Candida tropicalis ranks between third and fourth among Candida species most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives. Candida tropicalis is usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However, C. tropicalis resistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resistance mechanisms operating in C. tropicalis strains isolated from clinical samples showing resistance to azole drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal drug resistance was related to mutations of the azole target (Erg11p) with or without alterations of the ergosterol biosynthesis pathway. The antifungal drug resistance shown in vitro correlated very well with the results obtained in vivo using the model host Galleria mellonella. Using this panel of strains, the G. mellonella model system was validated as a simple, nonmammalian minihost model that can be used to study in vitro-in vivo correlation of antifungals in C. tropicalis. The development in C. tropicalis of antifungal drug resistance with different mechanisms during antifungal treatment has potential clinical impact and deserves specific prospective studies. PMID:23877676

  17. Isavuconazole: Pharmacology, Pharmacodynamics, and Current Clinical Experience with a New Triazole Antifungal Agent.

    PubMed

    Rybak, Jeffrey M; Marx, Kayleigh R; Nishimoto, Andrew T; Rogers, P David

    2015-11-01

    Coinciding with the continually increasing population of immunocompromised patients worldwide, the incidence of invasive fungal infections has grown over the past 4 decades. Unfortunately, infections caused by both yeasts such as Candida and molds such as Aspergillus or Mucorales remain associated with unacceptably high morbidity and mortality. In addition, the available antifungals with proven efficacy in the treatment of these infections remain severely limited. Although previously available second-generation triazole antifungals have significantly expanded the spectrum of the triazole antifungal class, these agents are laden with shortcomings in their safety profiles as well as formulation and pharmacokinetic challenges. Isavuconazole, administered as the prodrug isavuconazonium, is the latest second-generation triazole antifungal to receive U.S. Food and Drug Administration approval. Approved for the treatment of both invasive aspergillosis and invasive mucormycosis, and currently under investigation for the treatment of candidemia and invasive candidiasis, isavuconazole may have therapeutic advantages over its predecessors. With clinically relevant antifungal potency against a broad range of yeasts, dimorphic fungi, and molds, isavuconazole has a spectrum of activity reminiscent of the polyene amphotericin B. Moreover, clinical experience thus far has revealed isavuconazole to be associated with fewer toxicities than voriconazole, even when administered without therapeutic drug monitoring. These characteristics, in an agent available in both a highly bioavailable oral and a β-cyclodextrin-free intravenous formulation, will likely make isavuconazole a welcome addition to the triazole class of antifungals. PMID:26598096

  18. Antifungal agent utilization evaluation in hospitalized neutropenic cancer patients at a large teaching hospital

    PubMed Central

    Vazin, Afsaneh; Davarpanah, Mohammad Ali; Ghalesoltani, Setareh

    2015-01-01

    To evaluate pattern of using of three antifungal drugs: fluconazole, amphotericin B and voriconazole, at the hematology–oncology and bone marrow transplant wards of one large teaching hospital. In a prospective cross-sectional study, we evaluated the appropriateness of using antifungal drugs in patients, using Infectious Disease Society of America (IDSA) and National Comprehensive Cancer Network (NCCN) guidelines. All the data were recorded daily by a pharmacist in a form designed by a clinical pharmacist and infectious diseases specialist, for antifungals usage, administration, and monitoring. During the study, 116 patients were enrolled. Indications of prescribing amphotericin B, fluconazole, and voriconazole were appropriate according to guidelines in 83.4%, 80.6%, and 76.9% respectively. The duration of treatments were appropriate according to guidelines in 75%, 64.5%, and 71.1% respectively. The dose of voriconazole was appropriate according to guidelines in 46.2% of patients. None of the patients received salt loading before administration of amphotericin B. The most considerable problems with the mentioned antifungals were about the indications and duration of treatment. In addition, prehydration for amphotericin B and dosage of voriconazole were not completely compatible with the mentioned guidelines. A suitable combination of controlling the use of antifungals and educational programs could be essential for improving the general process of using antifungal drugs at our hospital. PMID:26064070

  19. In vitro antifungal activity and probable fungicidal mechanism of aqueous extract of Barleria grandiflora.

    PubMed

    Kumari, Suman; Jain, Preeti; Sharma, Bhawana; Kadyan, Preeti; Dabur, Rajesh

    2015-04-01

    Barleria grandiflora Dalz. (Acanthaceae) is being used in India to treat different types of disorders including skin infections. Therefore, there are good possibilities to find antifungal compounds in its extracts with novel mechanism of action. The main objectives of the present study were to evaluate the antifungal activity of plant extracts and to study its effects on metabolic pathways of A. fumigatus. The microbroth dilution assay was used to explore antifungal activity and MIC of various extracts. Metabolic profiles of control and treated cultures were collected from Q-TOF-MS interfaced with HPLC. Affected metabolic pathways of A. fumigatus after the treatment were analyzed by discrimination analysis of mass data. Antifungal activities were observed in hot and cold water extracts of the plant. Hot water extract of B. grandiflora showed significant activity against tested fungi in the range 0.625-1.25 mg/mL. Partial least discrimination analysis revealed that the hot water plant extract downregulated amino acid, glyoxylate pathway, and methylcitrate pathways at the same time due to the synergistic effects of secondary metabolites. Hot water extract also downregulated several other metabolic pathways unique to fungi indicating its specific activity toward fungi. B. grandiflora showed promising antifungal activity which can further be exploited by identification of active compounds, to inhibit the specific fungal pathways and development of novel therapeutic antifungal drugs. PMID:25672323

  20. Experimental models in predicting topical antifungal efficacy: practical aspects and challenges.

    PubMed

    Lai, J; Maibach, H I

    2009-01-01

    What are efficient screening models for improved topical antifungals? The use of minimum inhibitory concentrations (MICs) as one such parameter is discussed; we focus on the use of animal membranes for in vitro testing while highlighting the pros and cons of each model, exploring alternatives and discussing the importance of data transferability to humans and the influence of penetration kinetics in topical antifungal efficacy. Ultimately, the gold standard of testing is in vivo in humans; however, initiating with human testing, especially for novel topical antifungal agents, may be impractical, which is why we seek the ideal experimental model that most closely mimics human skin. We conclude that the pig may be an appropriate model membrane for topical antifungal testing based on its similarities in anatomical structure, physiology and permeation to human skin. Most importantly, pig and human skins appear equally permeable to several antifungals in prior in vitro and in vivo work. We do not discuss all prior work but highlight important issues in designing the protocol and parameters of the ideal experimental model for topical antifungals. PMID:19729988

  1. Antifungal activity of Zuccagnia punctata Cav.: evidence for the mechanism of action.

    PubMed

    Svetaz, Laura; Agüero, María Belén; Alvarez, Sandra; Luna, Lorena; Feresin, Gabriela; Derita, Marcos; Tapia, Alejandro; Zacchino, Susana

    2007-08-01

    Petroleum ether and dichloromethane extracts of fruits, aerial parts and exudate of Zuccagnia punctata Cav. (Fabaceae) showed moderate antifungal activities against the yeasts C. albicans, S. cerevisiae and C. neoformans (MICs: 62.5 - 250 microg/mL) and very strong antifungal activities against the dermatophytes M. gypseum, T. rubrum and T. mentagrophytes (MICs: 8 - 16 microg/mL) thus supporting the ethnopharmacological use of this plant. Antifungal activity-directed fractionation of active extracts by using bioautography led to the isolation of 2',4'-dihydroxy-3'-methoxychalcone (1) and 2',4'-dihydroxychalcone (2) as the compounds responsible for the antifungal activity. Second-order studies included MIC (80), MIC (50) and MFC of both chalcones in an extended panel of clinical isolates of the most sensitive fungi, and also comprised a series of targeted assays. They showed that the most active chalcone 2 is fungicidal rather than fungistatic, does not disrupt the fungal membranes up to 4 x MFC and does not act by inhibiting the fungal cell wall. So, 2',4'-dihydroxychalcone would act by a different mechanism of action than the antifungal drugs in current clinical use, such as amphotericin B, azoles or echinocandins, and thus appears to be very promising as a novel antifungal agent. PMID:17628836

  2. Isolation, characterization and antifungal docking studies of wortmannin isolated from Penicillium radicum

    PubMed Central

    Singh, Vineeta; Praveen, Vandana; Tripathi, Divya; Haque, Shafiul; Somvanshi, Pallavi; Katti, S. B.; Tripathi, C. K. M.

    2015-01-01

    During the search for a potent antifungal drug, a cell-permeable metabolite was isolated from a soil isolate taxonomically identified as Penicillium radicum. The strain was found to be a potent antifungal agent. Production conditions of the active compound were optimized and the active compound was isolated, purified, characterized and identified as a phosphoinositide 3-kinase (PI3K) inhibitor, commonly known as wortmannin (Wtmn). This is very first time we are reporting the production of Wtmn from P. radicum. In addition to its previously discovered anticancer properties, the broad spectrum antifungal property of Wtmn was re-confirmed using various fungal strains. Virtual screening was performed through molecular docking studies against potential antifungal targets, and it was found that Wtmn was predicted to impede the actions of these targets more efficiently than known antifungal compounds such as voriconazole and nikkomycin i.e. 1) mevalonate-5-diphosphate decarboxylase (1FI4), responsible for sterol/isoprenoid biosynthesis; 2) exocyst complex component SEC3 (3A58) where Rho- and phosphoinositide-dependent localization is present and 3) Kre2p/Mnt1p a Golgi alpha1,2-mannosyltransferase (1S4N) involved in the biosynthesis of yeast cell wall glycoproteins). We conclude that Wtmn produced from P. radicum is a promising lead compound which could be potentially used as an efficient antifungal drug in the near future after appropriate structural modifications to reduce toxicity and improve stability. PMID:26159770

  3. In vitro antifungal activity and mechanism of essential oil from fennel (Foeniculum vulgare L.) on dermatophyte species.

    PubMed

    Zeng, Hong; Chen, Xinping; Liang, Jingnan

    2015-01-01

    Fennel seed essential oil (FSEO) is a plant-derived natural therapeutic against dermatophytes. In this study, the antifungal effects of FSEO were investigated from varied aspects, such as MIC and minimum fungicidal concentration, mycelia growth, spore germination and biomass. The results indicated that FSEO had potent antifungal activities on Trichophyton rubrum ATCC 40051, Trichophyton tonsurans 10-0400, Microsporum gypseum 44693-1 and Trichophyton mentagrophytes 10-0060, which is better than the commonly used antifungal agents fluconazole and amphotericin B. Flow cytometry and transmission electron microscopy experiments suggested that the antifungal mechanism of FSEO was to damage the plasma membrane and intracellular organelles. Further study revealed that it could also inhibit the mitochondrial enzyme activities, such as succinate dehydrogenase, malate dehydrogenase and ATPase. With better antifungal activity than the commonly used antifungal agents and less possibility of inducing drug resistance, FSEO could be used as a potential antidermatophytic agent. PMID:25351709

  4. Searching new antifungals: The use of in vitro and in vivo methods for evaluation of natural compounds.

    PubMed

    Scorzoni, Liliana; Sangalli-Leite, Fernanda; de Lacorte Singulani, Junya; de Paula E Silva, Ana Carolina Alves; Costa-Orlandi, Caroline Barcelos; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares

    2016-04-01

    In the last decades, the increased number of immunocompromised patients has led to the emergence of many forms of fungal infections. Furthermore, there are a restricted arsenal of antifungals available and an increase in the development of resistance to antifungal drugs. Because of these disadvantages, the search for new antifungal agents in natural sources has increased. The development of these new antifungal drugs involves various steps and methodologies. The evaluation of the in vitro antifungal activity and cytotoxicity are the first steps in the screening. There is also the possibility of antifungal combinations to improve the therapy and reduce toxicity. Despite that, the application of the new antifungal candidate could be used in association with photodynamic therapy or using nanotechnology as an ally. In vivo tests can be performed to evaluate the efficacy and toxicity using conventional and alternative animal models. In this work, we review the methods available for the evaluation of the antifungal activity and safety of natural products, as well as the recent advances of new technology in the application of natural products for antifungal therapy. PMID:26853122

  5. [Antifungal activity of essential oils and their constituents against Candida spp. and their effects on activity of amphotericin B].

    PubMed

    Nozaki, Akiko; Takahashi, Eizo; Okamoto, Keinosuke; Ito, Hideyuki; Hatano, Tsutomu

    2010-06-01

    Candidiasis is a common opportunistic fungal infection that responds well to amphotericin B (AMPH) treatment. However, AMPH often causes adverse effects such as kidney injury and hypokalemia. Because some essential oils have been reported to have antifungal effects, we investigated the antifungal activity of various essential oils and their major constituents against Candida spp. Most essential oils examined in this study showed antifungal activity, and several enhanced the antifungal effect of AMPH. Clove oil in particular, and its major constituent eugenol, had potent effects. These findings suggest that combining certain essential oils or their constituents with AMPH may be useful for suppressing the adverse effects of AMPH treatment. PMID:20519869

  6. An Antifungal Benzimidazole Derivative Inhibits Ergosterol Biosynthesis and Reveals Novel Sterols

    PubMed Central

    Keller, Petra; Müller, Christoph; Engelhardt, Isabel; Hiller, Ekkehard; Lemuth, Karin; Eickhoff, Holger; Wiesmüller, Karl-Heinz; Burger-Kentischer, Anke; Bracher, Franz

    2015-01-01

    Fungal infections are a leading cause of morbidity and death for hospitalized patients, mainly because they remain difficult to diagnose and to treat. Diseases range from widespread superficial infections such as vulvovaginal infections to life-threatening systemic candidiasis. For systemic mycoses, only a restricted arsenal of antifungal agents is available. Commonly used classes of antifungal compounds include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapies, significant side effects, and high costs for several antifungals, there is a need for new antifungals in the clinic. In order to expand the arsenal of compounds with antifungal activity, we previously screened a compound library using a cell-based screening assay. A set of novel benzimidazole derivatives, including (S)-2-(1-aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole (EMC120B12), showed high antifungal activity against several species of pathogenic yeasts, including Candida glabrata and Candida krusei (species that are highly resistant to antifungals). In this study, comparative analysis of EMC120B12 versus fluconazole and nocodazole, using transcriptional profiling and sterol analysis, strongly suggested that EMC120B12 targets Erg11p in the ergosterol biosynthesis pathway and not microtubules, like other benzimidazoles. In addition to the marker sterol 14-methylergosta-8,24(28)-dien-3β,6α-diol, indicating Erg11p inhibition, related sterols that were hitherto unknown accumulated in the cells during EMC120B12 treatment. The novel sterols have a 3β,6α-diol structure. In addition to the identification of novel sterols, this is the first time that a benzimidazole structure has been shown to result in a block of the ergosterol pathway. PMID:26248360

  7. An Antifungal Benzimidazole Derivative Inhibits Ergosterol Biosynthesis and Reveals Novel Sterols.

    PubMed

    Keller, Petra; Müller, Christoph; Engelhardt, Isabel; Hiller, Ekkehard; Lemuth, Karin; Eickhoff, Holger; Wiesmüller, Karl-Heinz; Burger-Kentischer, Anke; Bracher, Franz; Rupp, Steffen

    2015-10-01

    Fungal infections are a leading cause of morbidity and death for hospitalized patients, mainly because they remain difficult to diagnose and to treat. Diseases range from widespread superficial infections such as vulvovaginal infections to life-threatening systemic candidiasis. For systemic mycoses, only a restricted arsenal of antifungal agents is available. Commonly used classes of antifungal compounds include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapies, significant side effects, and high costs for several antifungals, there is a need for new antifungals in the clinic. In order to expand the arsenal of compounds with antifungal activity, we previously screened a compound library using a cell-based screening assay. A set of novel benzimidazole derivatives, including (S)-2-(1-aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole (EMC120B12), showed high antifungal activity against several species of pathogenic yeasts, including Candida glabrata and Candida krusei (species that are highly resistant to antifungals). In this study, comparative analysis of EMC120B12 versus fluconazole and nocodazole, using transcriptional profiling and sterol analysis, strongly suggested that EMC120B12 targets Erg11p in the ergosterol biosynthesis pathway and not microtubules, like other benzimidazoles. In addition to the marker sterol 14-methylergosta-8,24(28)-dien-3β,6α-diol, indicating Erg11p inhibition, related sterols that were hitherto unknown accumulated in the cells during EMC120B12 treatment. The novel sterols have a 3β,6α-diol structure. In addition to the identification of novel sterols, this is the first time that a benzimidazole structure has been shown to result in a block of the ergosterol pathway. PMID:26248360

  8. In vitro antifungal susceptibility testing of Scopulariopsis brevicaulis strains using agar diffusion method.

    PubMed

    Skóra, Magdalena; Macura, Anna B

    2011-01-01

    The genus Scopulariopsis is a common soil saprotroph and has been isolated from air, organic waste and also from plant, animal and human tissues. Scopulariopsis has mainly been associated in humans with superficial mycoses, but it has also been described as the cause of subcutaneous and invasive infections. The most common aetiological agent of infections in humans is Scopulariopsis brevicaulis. This species has been reported to be resistant in vitro to broad-spectrum antifungal agents available today. The aim of the study was to establish in vitro antifungal susceptibility of 35 S. brevicaulis strains against amphotericin B (AMB), flucytosine (FC), caspofungin (CAS), terbinafine (TER), ciclopirox (CIC), voriconazole (VOR), clotrimazole (CTR), miconazole (MCZ), econazole (ECO), ketoconazole (KET), itraconazole (ITR), and fluconazole (FLU). Antifungal susceptibility tests were evaluated by an agar diffusion method (Neo-Sensitabs, Rosco, Denmark). AMB, FC, CAS, ITR and FLU showed no antifungal activity against S. brevicaulis. TER, CIC, CTR, KET, VOR, ECO, and MCZ revealed inhibitory activity for S. brevicaulis, but it varied for each of the drugs. The best antifungal effect was observed for TER and CIC. All isolates had large inhibition zones for TER and CIC. CTR was also inhibitory for all tested S. brevicaulis isolates, but the diameters of inhibition zones were smaller than for TER and CIC. Nearly 89% isolates showed inhibition zones for KET and the mean diameter of the inhibition zone was comparable to CTR. The least antifungal activity exhibited VQR, ECO and MCZ. Because of the multiresistance of S. brevicaulis, infections due to this species may not respond to particular antifungal treatment and other therapeutic approaches should be considered, e.g., combined therapy and/or surgery. PMID:21682097

  9. Forest soil metagenome gene cluster involved in antifungal activity expression in Escherichia coli.

    PubMed

    Chung, Eu Jin; Lim, He Kyoung; Kim, Jin-Cheol; Choi, Gyung Ja; Park, Eun Jin; Lee, Myung Hwan; Chung, Young Ryun; Lee, Seon-Woo

    2008-02-01

    Using two forest soils, we previously constructed two fosmid libraries containing 113,700 members in total. The libraries were screened to select active antifungal clones using Saccharomyces cerevisiae as a target fungus. One clone from the Yuseong pine tree rhizosphere soil library, pEAF66, showed S. cerevisiae growth inhibition. Despite an intensive effort, active chemicals were not isolated. DNA sequence analysis and transposon mutagenesis of pEAF66 revealed 39 open reading frames (ORFs) and indicated that eight ORFs, probably in one transcriptional unit, might be directly involved in the expression of antifungal activity in Escherichia coli. The deduced amino acid sequences of eight ORFs were similar to those of the core genes encoding type II family polyketide synthases, such as the acyl carrier protein (ACP), ACP synthases, aminotransferase, and ACP reductase. The gene cluster involved in antifungal activity was similar in organization to the putative antibiotic production locus of Pseudomonas putida KT2440, although we could not select a similar active clone from the KT2440 genomic DNA library in E. coli. ORFs encoding ATP binding cassette transporters and membrane proteins were located at both ends of the antifungal gene cluster. Upstream ORFs encoding an IclR family response regulator and a LysR family response regulator were involved in the positive regulation of antifungal gene expression. Our results suggested the metagenomic approach as an alternative to search for novel antifungal antibiotics from unculturable soil bacteria. This is the first report of an antifungal gene cluster obtained from a soil metagenome using S. cerevisiae as a target fungus. PMID:18065615

  10. Antiproliferative effect and characterization of a novel antifungal peptide derived from human Chromogranin A

    PubMed Central

    LI, RUI-FANG; LU, YA-LI; LU, YAN-BO; ZHANG, HUI-RU; HUANG, LIANG; YIN, YANLI; ZHANG, LIN; LIU, SHUAI; LU, ZHIFANG; SUN, YANAN

    2015-01-01

    CGA-N46 is a novel antifungal peptide derived from the N-terminus of human Chromogranin A, corresponding to the 31st to 76th amino acids. Further research on its activities and characteristics may be helpful for the application of CGA-N46 in medical or other situations. In the present study, the antifungal spectrum and physicochemical characteristics of CGA-N46 were investigated using an antifungal assay, its antiproliferative effects on cancer and normal cells were assessed using MTT assay and its combinatorial effect with other antibiotics was analyzed using checkerboard analysis. The results showed that CGA-N46 exhibited antifungal activity against the tested Candidas (C. glabrata, C. parapsilosis, C. krusei, C. tropicalis and C. albicans) at a concentration of <0.8 mM, but had no effect on the growth of filamentous fungi or other types of fungi (Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Fusarium moniliforme, Microsporum canis, Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes), even at a concentration of 3.2 mM. CGA-N46 had an inhibitory effect on the proliferation of lung cancer A549 cells and a reversible effect on the growth of normal primary chicken embryo fibroblast cells, but no hemolytic activity on human erythrocytes at the minimum inhibitory concentration of CGA-N46 against yeasts. The antifungal activity of CGA-N46 was stable at a temperature <40°C or within a broad pH range (pH 5.0–7.0). Its antifungal activity was enhanced when the peptide was used in combination with fluconazole and terbinafine. The present results indicate that CGA-N46 is a safe, physicochemically stable, antifungal peptide with anticancer cell activity that exhibits an additive effect with conventional antibiotics. PMID:26668630

  11. Screening of Pharmacologically Active Small Molecule Compounds Identifies Antifungal Agents Against Candida Biofilms

    PubMed Central

    Watamoto, Takao; Egusa, Hiroshi; Sawase, Takashi; Yatani, Hirofumi

    2015-01-01

    Candida species have emerged as important and common opportunistic human pathogens, particularly in immunocompromised individuals. The current antifungal therapies either have toxic side effects or are insufficiently effect. The aim of this study is develop new small-molecule antifungal compounds by library screening methods using Candida albicans, and to evaluate their antifungal effects on Candida biofilms and cytotoxic effects on human cells. Wild-type C. albicans strain SC5314 was used in library screening. To identify antifungal compounds, we screened a small-molecule library of 1,280 pharmacologically active compounds (LOPAC1280TM) using an antifungal susceptibility test (AST). To investigate the antifungal effects of the hit compounds, ASTs were conducted using Candida strains in various growth modes, including biofilms. We tested the cytotoxicity of the hit compounds using human gingival fibroblast (hGF) cells to evaluate their clinical safety. Only 35 compounds were identified by screening, which inhibited the metabolic activity of C. albicans by >50%. Of these, 26 compounds had fungistatic effects and nine compounds had fungicidal effects on C. albicans. Five compounds, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate, ellipticine and CV-3988, had strong fungicidal effects and could inhibit the metabolic activity of Candida biofilms. However, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine were cytotoxic to hGF cells at low concentrations. CV-3988 showed no cytotoxicity at a fungicidal concentration. Four of the compounds identified, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine, had toxic effects on Candida strains and hGF cells. In contrast, CV-3988 had fungicidal effects on Candida strains, but low cytotoxic effects on hGF cells. Therefore, this screening reveals agent, CV-3988 that was previously unknown to be antifungal agent, which could be a novel therapies for superficial mucosal candidiasis. PMID

  12. Training should be the first step toward an antifungal stewardship program.

    PubMed

    Valerio, Maricela; Muñoz, Patricia; Rodríguez-González, Carmen; Sanjurjo, María; Guinea, Jesús; Bouza, Emilio

    2015-04-01

    The frequency of use of systemic antifungal agents has increased significantly in most tertiary centers. However, antifungal stewardship has received very little attention. The objective of this article was to assess the knowledge of prescribing physicians in our institution as a first step in the development of an antifungal stewardship program. Attending physicians from the departments that prescribe most antifungals were invited to complete a questionnaire based on current guidelines on diagnosis and therapy of invasive candidiasis and invasive aspergillosis (IA). The survey was completed by 60.8% (200/329) of the physicians who were invited to participate. The physicians belonged to the following departments: medical (60%), pediatric (19%), intensive care (15.5%), and surgical (5.5%). The mean (±SD) score of correct responses was 5.16±1.73. In the case of candidiasis, only 55% of the physicians clearly distinguished between colonization and infection, and 17.5% knew the local rate of fluconazole resistance. Thirty-three percent knew the accepted indications for antifungal prophylaxis, and 23% the indications for empirical therapy. However, most physicians knew which antifungals to choose when starting empirical therapy (73.5%). As for aspergillosis, most physicians (67%) could differentiate between colonization and infection, and 34.5% knew the diagnostic value of galactomannan. The radiological features of IA were well recognized by 64%, but only 31.5% were aware of the first line of treatment for IA, and 36% of the recommended duration of therapy. The usefulness of antifungal levels was known by 67%. This simple, easily completed questionnaire enabled us to identify which areas of our training strategy could be improved. PMID:25066382

  13. Antifungal, phytotoxic and toxic metabolites produced by Penicillium purpurogenum.

    PubMed

    Li, He; Wei, Jing; Pan, Shi-Yin; Gao, Jin-Ming; Tian, Jun-Mian

    2014-01-01

    Nine known metabolites, 6,8,1'-tri-O-methyl averantin (1), 6,8-di-O-methyl averufnin (2), 6,8-di-O-methyl averufanin (3), aversin (4), 1,3-dihydroxy-6,8-dimethoxy-9,10-anthraquinone (5), 6,8-di-O-methylnidurufin (6), 6,8-di-O-methyl versiconol (7), 5-methyoxysterigmatocystin (8) and (S)-ornidazole (9), were isolated from the extracts of Penicillium purpurogenum, and their structures were elucidated by using spectroscopic methods. The brine shrimp toxicity, anti-phytopathogenic and phytotoxic effects of these compounds were evaluated. Among them, compounds 1 and 8 exhibited the strongest toxicity against brine shrimp (Artemia salina), with lethality rates of 100% at a low concentration of 10 μM, comparable to the positive control toosendanin. Compounds 1, 4 and 7 moderately inhibited the growth of Botrytis cinerea. Moreover, 4 displayed moderate antifungal effects on Gibberella saubinettii. In addition, compounds 6, 7 and 9 produced the phytotoxic effects on radish seedlings at 100 μM. This is the first report on the isolation of these metabolites from this organism. PMID:25103412

  14. A9145, a New Adenine-Containing Antifungal Antibiotic: Fermentation

    PubMed Central

    Boeck, L. D.; Clem, G. M.; Wilson, M. M.; Westhead, J. E.

    1973-01-01

    A9145 is a basic, water-soluble, antifungal antibiotic which is produced in a complex organic medium by Streptomyces griseolus. The metabolite has a molecular weight of 510, and contains adenine as well as sugar hydroxyl and amino groups. Although glucose, fructose, glucose polymers, and some long-chain fatty acid methyl esters supported biosynthesis, oils were superior, with cottonseed oil being preferred. Several ions and salts, especially Co2+, PO43−, and CaCO3, were stimulatory. Adenine, nucleosides, and some amino acids increased the accumulation of A9145 in shaken-flask fermentors. Enrichment of the culture medium with tyrosine afforded maximal enhancement of antibiotic production in both flask and tank fermentors. Control of the dissolved O2 level was also critical, the optimal concentration being 3 × 10−2 to 4.5 × 10−2 μmole of O2/ml. Optimization of various fermentation parameters increased antibiotic titers approximately 135-fold in shaken flask fermentors and 225-fold in stirred vessels. PMID:4208279

  15. Antifungal and antibacterial activities of Petroselinum crispum essential oil.

    PubMed

    Linde, G A; Gazim, Z C; Cardoso, B K; Jorge, L F; Tešević, V; Glamoćlija, J; Soković, M; Colauto, N B

    2016-01-01

    Parsley [Petroselinum crispum (Mill.) Fuss] is regarded as an aromatic, culinary, and medicinal plant and is used in the cosmetic, food, and pharmaceutical industries. However, few studies with conflicting results have been conducted on the antimicrobial activity of parsley essential oil. In addition, there have been no reports of essential oil obtained from parsley aerial parts, except seeds, as an alternative natural antimicrobial agent. Also, microorganism resistance is still a challenge for health and food production. Based on the demand for natural products to control microorganisms, and the re-evaluation of potential medicinal plants for controlling diseases, the objective of this study was to determine the chemical composition and antibacterial and antifungal activities of parsley essential oil against foodborne diseases and opportunistic pathogens. Seven bacteria and eight fungi were tested. The essential oil major compounds were apiol, myristicin, and b-phellandrene. Parsley essential oil had bacteriostatic activity against all tested bacteria, mainly Staphylococcus aureus, Listeria monocytogenes, and Salmonella enterica, at similar or lower concentrations than at least one of the controls, and bactericidal activity against all tested bacteria, mainly S. aureus, at similar or lower concentrations than at least one of the controls. This essential oil also had fungistatic activity against all tested fungi, mainly, Penicillium ochrochloron and Trichoderma viride, at lower concentrations than the ketoconazole control and fungicidal activity against all tested fungi at higher concentrations than the controls. Parsley is used in cooking and medicine, and its essential oil is an effective antimicrobial agent. PMID:27525894

  16. Azospirillum brasilense siderophores with antifungal activity against Colletotrichum acutatum.

    PubMed

    Tortora, María L; Díaz-Ricci, Juan C; Pedraza, Raúl O

    2011-04-01

    Anthracnose, caused by the fungus Colletotrichum acutatum is one of the most important diseases in strawberry crop. Due to environmental pollution and resistance produced by chemical fungicides, nowadays biological control is considered a good alternative for crop protection. Among biocontrol agents, there are plant growth-promoting bacteria, such as members of the genus Azospirillum. In this work, we demonstrate that under iron limiting conditions different strains of A. brasilense produce siderophores, exhibiting different yields and rates of production according to their origin. Chemical assays revealed that strains REC2 and REC3 secrete catechol type siderophores, including salicylic acid, detected by thin layer chromatography coupled with fluorescence spectroscopy and gas chromatography-mass spectrometry analysis. Siderophores produced by them showed in vitro antifungal activity against C. acutatum M11. Furthermore, this latter coincided with results obtained from phytopathological tests performed in planta, where a reduction of anthracnose symptoms on strawberry plants previously inoculated with A. brasilense was observed. These outcomes suggest that some strains of A. brasilense could act as biocontrol agent preventing anthracnose disease in strawberry. PMID:21234749

  17. Standardization of antifungal susceptibility variables for a semiautomated methodology.

    PubMed

    Rodríguez-Tudela, J L; Cuenca-Estrella, M; Díaz-Guerra, T M; Mellado, E

    2001-07-01

    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: (i) accuracy of inoculum preparation, (ii) correlation between optical density and CFU per milliliter, (iii) influence of the wavelength on the endpoint determination, and (iv) influence of the dimethyl sulfoxide concentration on the growth kinetics. The main results can be summarized as follows: (i) inoculum preparation following the methodology recommended by the National Committee for Clinical Laboratory Standards is an exact procedure; (ii) the relationship between optical density and CFU per milliliter is linear (coefficient of determination, r(2) = 0.84); (iii) MICs obtained by means of spectrophotometric readings at different wavelengths are identical (for amphotericin B, an intraclass correlation coefficient of 0.98 was obtained; for fluconazole, the intraclass correlation coefficient was 1); and (iv) a 2% concentration of dimethyl sulfoxide produces a significantly slower and lower growth curve of Candida spp. than other concentrations. PMID:11427562

  18. Mono- and sesquiterpenes and antifungal constituents from Artemisia species.

    PubMed

    Tan, R X; Lu, H; Wolfender, J L; Yu, T T; Zheng, W F; Yang, L; Gafner, S; Hostettmann, K

    1999-02-01

    In addition to beta-sitosterol and alpha-amyrin detected in all the investigated species, the extract of the aerial parts of Artemisia giraldii var. giraldii gave stigmasterol, daucosterol, sesamine, luteolin, eupafolin, hispidulin, eupatilin, belamcanidin, pinitol, artemin, ridentin, and a new antifungal monoterpene (named santolinylol) while that of the aerial parts of A. mongolica afforded sesamine, eupafolin, eupatilin, matricarin, and a new germacranolide (3-oxo-11 alpha H-germacra-1(10)E,4Z-dien-12,6 alpha-olide), and that of the aerial parts of A. vestita yielded stigmasterol, daucosterol, umbelliferone, scopolin, scoparone, and isoscopoletin-O-glucoside. Pinitol, first reisolated from Artemisia genus, was shown to inhibit the growth of the human pathogenic fungi Candida albicans, Aspergillus flavus, A. niger, Geotrichun candidum, Trichophyton rubrum, and Epidermophyton floccosum. Umbelliferone was also active against Candida tropicalis, A. flavus, G. candidum, T. rubrum, and E. floccosum. The flavones hispidulin and belamcanidin were almost equally inhibitory to the growth of A. flavus, G. candidum, T. rubrum, and E. floccosum, and santolinylol to C. albicans, A. flavus, A. niger, G. candidum, T. rubrum, and E. floccosum. In addition, ridentin was active against the growth of the plant pathogenic fungus Cladosporium cucumerinum. PMID:10083848

  19. Aleuria aurantia lectin exhibits antifungal activity against Mucor racemosus.

    PubMed

    Amano, Koh; Katayama, Hiroe; Saito, Akihiro; Ando, Akikazu; Nagata, Yoshiho

    2012-01-01

    Aleuria aurantia lectin (AAL) is an L-fucose-specific lectin produced in the mycelia and fruit-bodies of the widespread ascomycete fungus Aleuria aurantia. It is extensively used in the detection of fucose, but its physiological role remains unknown. To investigate this, we analyzed the interaction between AAL and, a zygomycete fungus Mucor racemosus, which is assumed to contain fucose in its cell wall. AAL specifically bound to the hyphae of M. racemosus, because binding was inhibited by L-fucose but not by D-fucose. It inhibited the growth of the fungus at 1 µM, and the M. racemosus cells were remarkably disrupted at 7.5 µM. In contrast, two other fucose-specific lectins, Anguilla anguilla agglutinin and Ulex europaeus agglutinin, did not inhibit the growth of M. racemosus. These results suggest that the growth inhibition activity is unique to AAL, and that AAL could act as an antifungal protein in natural ecosystems. PMID:22738968

  20. Antifungal and antibacterial activities of Taxus wallichiana Zucc.

    PubMed

    Nisar, Muhammad; Khan, Inamullah; Ahmad, Bashir; Ali, Ihsan; Ahmad, Waqar; Choudhary, Muhammad Iqbal

    2008-04-01

    Current study was undertaken to evaluate the in vitro antifungal and antibacterial potential of methanol extract and subsequent fractions obtained after partitioning in organic solvents with variable polarity of the aerial parts of the tree Taxus wallichiana Zucc. Traditionally, this plant is often used in folk medicines in Pakistan for treating microbial infections. In order to rationalize the traditional use, methanol extracts of leaf, bark, and heartwood of Taxus wallichiana Zucc. were tested against six bacteria and six fungal strains using the Hole diffusion and macro-dilution methods. All extracts and fractions displayed significant antimicrobial effect. Only three fungal strains, Trichophyton longifusus, Microspoum canis, and Fusarium solani were susceptible to the extracts and fractions with MICs ranging from 0.08 to 200 mg/mL. In case of bacterial strains, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi were susceptible to the extracts and fractions with MICs ranging from 0.08 to 200 mg/mL. Comparison results were carried out using imipinem, miconazole and amphotericin B as standard antibiotics. PMID:18343912

  1. Antifungal Effect of Essential Oils against Fusarium Keratitis Isolates.

    PubMed

    Homa, Mónika; Fekete, Ildikó Pálma; Böszörményi, Andrea; Singh, Yendrembam Randhir Babu; Selvam, Kanesan Panneer; Shobana, Coimbatore Subramanian; Manikandan, Palanisamy; Kredics, László; Vágvölgyi, Csaba; Galgóczy, László

    2015-09-01

    The present study was carried out to investigate the antifungal effects of Cinnamomum zeylanicum, Citrus limon, Juniperus communis, Eucalyptus citriodora, Gaultheria procumbens, Melaleuca alternifolia, Origanum majorana, Salvia sclarea, and Thymus vulgaris essential oils against Fusarium species, the most common etiologic agents of filamentous fungal keratitis in South India. C. zeylanicum essential oil showed strong anti-Fusarium activity, whereas all the other tested essential oils proved to be less effective. The main component of C. zeylanicum essential oil, trans-cinnamaldehyde, was also tested and showed a similar effect as the oil. The in vitro interaction between trans-cinnamaldehyde and natamycin, the first-line therapeutic agent of Fusarium keratitis, was also investigated; an enhanced fungal growth inhibition was observed when these agents were applied in combination. Light and fluorescent microscopic observations revealed that C. zeylanicum essential oil/trans-cinnamaldehyde reduces the cellular metabolism and inhibits the conidia germination. Furthermore, necrotic events were significantly more frequent in the presence of these two compounds. According to our results, C. zeylanicum essential oil/trans-cinnamaldehyde provides a promising basis to develop a novel strategy for the treatment of Fusarium keratitis. PMID:26227503

  2. Synthesis and antifungal activities of novel polyheterocyclic spirooxindole derivatives.

    PubMed

    Wu, Jia-Shou; Zhang, Xue; Zhang, Ying-Lao; Xie, Jian-Wu

    2015-05-01

    A series of spirooxindole tetrahydrofuran derivatives 3 were obtained in moderate to good yields via oxindole derivatives 1 and β-arylacrylonitrile derivatives 2via base-mediated cascade [3 + 2] double Michael reactions under mild conditions and the application of this method in the synthesis of bioactive analogues, such as functionalized spirooxindole octahydrofuro[3,4-c]pyridine derivatives 4 which contain two new heterocyclic rings and two quaternary carbon centers, has also been developed. Subsequently, antifungal activities of all of the synthesized compounds were evaluated against five phytopathogenic fungi (Rhizoctonia solani, Fusarium semitectum, Alternaria solani, Valsa mali and Fusarium graminearum) using the mycelium growth rate method. The preliminary results showed that the spirooxindole octahydrofuro[3,4-c]pyridine derivative 4 showed higher growth inhibition of Valsa mali and Fusarium graminearum, than spirooxindole tetrahydrofuran derivatives 3. For example, spirooxindole octahydrofuro[3,4-c]pyridine derivative 4ab, having a bromine atom at the meta position of the benzene ring, was the best compound in inhibiting F. g. with an IC50 value of 3.31, in particular with inhibition of 4ab on F. g. being similar to that of the control cycloheximide (IC50 = 3.3 μg mL(-1)). PMID:25820179

  3. Subterranean termite prophylactic secretions and external antifungal defenses.

    PubMed

    Hamilton, Casey; Lay, Frank; Bulmer, Mark S

    2011-09-01

    Termites exploit environments that make them susceptible to infection and rapid disease transmission. Gram-negative bacteria binding proteins (GNBPs) signal the presence of microbes and in some insects directly damage fungal pathogens with β-1,3-glucanase activity. The subterranean termites Reticulitermes flavipes and Reticulitermes virginicus encounter soil entomopathogenic fungi such as Metarhizium anisopliae, which can evade host immune responses after penetrating the cuticle. An external defense that prevents invasion of fungal pathogens could be crucial in termites, allowing them to thrive under high pathogenic pressures. We investigated the role of secreted β-1,3-glucanases in Reticulitermes defenses against M. anisopliae. Our results show that these termites secrete antifungal β-1,3-glucanases on the cuticle, and the specific inhibition of GNBP associated β-1,3-glucanase activity with d-δ-gluconolactone (GDL) reduces this activity and can cause significant increases in mortality after exposure to M. anisopliae. Secreted β-1,3-glucanases appear to be essential in preventing infection by breaking down fungi externally. PMID:21708164

  4. Nest sanitation through defecation: antifungal properties of wood cockroach feces

    NASA Astrophysics Data System (ADS)

    Rosengaus, Rebeca B.; Mead, Kerry; Du Comb, William S.; Benson, Ryan W.; Godoy, Veronica G.

    2013-11-01

    The wood cockroach Cryptocercus punctulatus nests as family units inside decayed wood, a substrate known for its high microbial load. We tested the hypothesis that defecation within their nests, a common occurrence in this species, reduces the probability of fungal development. Conidia of the entomopathogenic fungus, Metarhizium anisopliae, were incubated with crushed feces and subsequently plated on potato dextrose agar. Relative to controls, the viability of fungal conidia was significantly reduced following incubation with feces and was negatively correlated with incubation time. Although the cockroach's hindgut contained abundant β-1,3-glucanase activity, its feces had no detectable enzymatic function. Hence, these enzymes are unlikely the source of the fungistasis. Instead, the antifungal compound(s) of the feces involved heat-sensitive factor(s) of potential microbial origin. When feces were boiled or when they were subjected to ultraviolet radiation and subsequently incubated with conidia, viability was "rescued" and germination rates were similar to those of controls. Filtration experiments indicate that the fungistatic activity of feces results from chemical interference. Because Cryptocercidae cockroaches have been considered appropriate models to make inferences about the factors fostering the evolution of termite sociality, we suggest that nesting in microbe-rich environments likely selected for the coupling of intranest defecation and feces fungistasis in the common ancestor of wood cockroaches and termites. This might in turn have served as a preadaptation that prevented mycosis as these phylogenetically related taxa diverged and evolved respectively into subsocial and eusocial organizations.

  5. Antifungal activity of redox-active benzaldehydes that target cellular antioxidation

    PubMed Central

    2011-01-01

    Background Disruption of cellular antioxidation systems should be an effective method for control of fungal pathogens. Such disruption can be achieved with redox-active compounds. Natural phenolic compounds can serve as potent redox cyclers that inhibit microbial growth through destabilization of cellular redox homeostasis and/or antioxidation systems. The aim of this study was to identify benzaldehydes that disrupt the fungal antioxidation system. These compounds could then function as chemosensitizing agents in concert with conventional drugs or fungicides to improve antifungal efficacy. Methods Benzaldehydes were tested as natural antifungal agents against strains of Aspergillus fumigatus, A. flavus, A. terreus and Penicillium expansum, fungi that are causative agents of human invasive aspergillosis and/or are mycotoxigenic. The yeast Saccharomyces cerevisiae was also used as a model system for identifying gene targets of benzaldehydes. The efficacy of screened compounds as effective chemosensitizers or as antifungal agents in formulations was tested with methods outlined by the Clinical Laboratory Standards Institute (CLSI). Results Several benzaldehydes are identified having potent antifungal activity. Structure-activity analysis reveals that antifungal activity increases by the presence of an ortho-hydroxyl group in the aromatic ring. Use of deletion mutants in the oxidative stress-response pathway of S. cerevisiae (sod1Δ, sod2Δ, glr1Δ) and two mitogen-activated protein kinase (MAPK) mutants of A. fumigatus (sakAΔ, mpkCΔ), indicates antifungal activity of the benzaldehydes is through disruption of cellular antioxidation. Certain benzaldehydes, in combination with phenylpyrroles, overcome tolerance of A. fumigatus MAPK mutants to this agent and/or increase sensitivity of fungal pathogens to mitochondrial respiration inhibitory agents. Synergistic chemosensitization greatly lowers minimum inhibitory (MIC) or fungicidal (MFC) concentrations. Effective

  6. Antifungal activities of diphenyl diselenide and ebselen alone and in combination with antifungal agents against Fusarium spp.

    PubMed

    Venturini, Tarcieli Pozzebon; Chassot, Francieli; Loreto, Érico Silva; Keller, Jéssica Tairine; Azevedo, Maria Izabel; Zeni, Gilson; Santurio, Janio Morais; Alves, Sydney Hartz

    2016-07-01

    Herein, we describe the in vitro activity of a combination of the organoselenium compounds diphenyl diselenide and ebselen alone and in combination with amphotericin B, caspofungin, itraconazole, and voriconazole against 25 clinical isolates of Fusarium spp. For this analysis, we used the broth microdilution method based on the M38-A2 technique and checkerboard microdilution method. Diphenyl diselenide (MIC range = 4-32 μg/ml) and ebselen (MIC range = 2-8 μg/ml) showed in vitro activity against the isolates tested. The most effective combinations were (synergism rates): ebselen + amphotericin B (88%), ebselen + voriconazole (80%), diphenyl diselenide + amphotericin B (72%), and diphenyl diselenide + voriconazole (64%). Combination with caspofungin resulted in low rates of synergism: ebselen + caspofungin, 36%, and diphenyl diselenide + caspofungin, 28%; combination with itraconazole demonstrated indifferent interactions. Antagonistic effects were not observed for any of the combinations tested. Our findings suggest that the antifungal potential of diphenyl diselenide and ebselen deserves further investigation in in vivo experimental models, especially in combination with amphotericin B and voriconazole. PMID:26773133

  7. Gene Expression Response of Trichophyton rubrum during Coculture on Keratinocytes Exposed to Antifungal Agents

    PubMed Central

    Komoto, Tatiana Takahasi; Bitencourt, Tamires Aparecida; Silva, Gabriel; Beleboni, Rene Oliveira; Marins, Mozart; Fachin, Ana Lúcia

    2015-01-01

    Trichophyton rubrum is the most common causative agent of dermatomycoses worldwide, causing infection in the stratum corneum, nails, and hair. Despite the high prevalence of these infections, little is known about the molecular mechanisms involved in the fungal-host interaction, particularly during antifungal treatment. The aim of this work was to evaluate the gene expression of T. rubrum cocultured with keratinocytes and treated with the flavonoid trans-chalcone and the glycoalkaloid α-solanine. Both substances showed a marked antifungal activity against T. rubrum strain CBS (MIC = 1.15 and 17.8 µg/mL, resp.). Cytotoxicity assay against HaCaT cells produced IC50 values of 44.18 to trans-chalcone and 61.60 µM to α-solanine. The interaction of keratinocytes with T. rubrum conidia upregulated the expression of genes involved in the glyoxylate cycle, ergosterol synthesis, and genes encoding proteases but downregulated the ABC transporter TruMDR2 gene. However, both antifungals downregulated the ERG1 and ERG11, metalloprotease 4, serine proteinase, and TruMDR2 genes. Furthermore, the trans-chalcone downregulated the genes involved in the glyoxylate pathway, isocitrate lyase, and citrate synthase. Considering the urgent need for more efficient and safer antifungals, these results contribute to a better understanding of fungal-host interactions and to the discovery of new antifungal targets. PMID:26257814

  8. Quantitative Microplate-Based Growth Assay for Determination of Antifungal Susceptibility of Histoplasma capsulatum Yeasts

    PubMed Central

    Goughenour, Kristie D.; Balada-Llasat, Joan-Miquel

    2015-01-01

    Standardized methodologies for determining the antifungal susceptibility of fungal pathogens is central to the clinical management of invasive fungal disease. Yeast-form fungi can be tested using broth macrodilution and microdilution assays. Reference procedures exist for Candida species and Cryptococcus yeasts; however, no standardized methods have been developed for testing the antifungal susceptibility of yeast forms of the dimorphic systemic fungal pathogens. For the dimorphic fungal pathogen Histoplasma capsulatum, susceptibility to echinocandins differs for the yeast and the filamentous forms, which highlights the need to employ Histoplasma yeasts, not hyphae, in antifungal susceptibility tests. To address this, we developed and optimized methodology for the 96-well microtiter plate-based measurement of Histoplasma yeast growth in vitro. Using optical density, the assay is quantitative for fungal growth with a dynamic range greater than 30-fold. Concentration and assay reaction time parameters were also optimized for colorimetric (MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] reduction) and fluorescent (resazurin reduction) indicators of fungal vitality. We employed this microtiter-based assay to determine the antifungal susceptibility patterns of multiple clinical isolates of Histoplasma representing different phylogenetic groups. This methodology fulfills a critical need for the ability to monitor the effectiveness of antifungals on Histoplasma yeasts, the morphological form present in mammalian hosts and, thus, the form most relevant to disease. PMID:26246483

  9. Antifungal prophylaxis in lung transplantation--a world-wide survey.

    PubMed

    Neoh, C F; Snell, G I; Kotsimbos, T; Levvey, B; Morrissey, C O; Slavin, M A; Stewart, K; Kong, D C M

    2011-02-01

    While variations in antifungal prophylaxis have been previously reported in lung transplant (LTx) recipients, recent clinical practice is unknown. Our aim was to determine current antifungal prophylactic practice in LTx centers world-wide. One nominated LTx clinician from each active center was invited by e-mail to participate in a web-based survey between September 2009 and January 2010. Fifty-seven percent (58/102) responded. The majority of responses were from medical directors of LTx centers (72.4%), and from the United States (44.8%). Within the first 6 months post-LTx, most centers (58.6%) employed universal prophylaxis, with 97.1% targeting Aspergillus species. Voriconazole alone, and in combination with inhaled amphotericin B (AmB), were the preferred first-line agents. Intolerance to side effects of voriconazole (69.2%) was the main reason for switching to alternatives. Beyond 6 months post-LTx, most (51.8%) did not employ antifungal prophylaxis. Fifteen centers (26.0%) conducted routine antifungal therapeutic drug monitoring during prophylactic period. There are differences in strategies employed between U.S. and European centers. Most respondents indicated a need for antifungal prophylactic guidelines. In comparison to earlier findings, there was a major shift toward prophylaxis with voriconazole and an increased use of echinocandins, posaconazole and inhaled lipid formulation AmB. PMID:21272239

  10. Isolation and identification of antifungal peptides from Bacillus BH072, a novel bacterium isolated from honey.

    PubMed

    Zhao, Xin; Zhou, Zhi-jiang; Han, Ye; Wang, Zhan-zhong; Fan, Jie; Xiao, Hua-zhi

    2013-11-01

    A bacterial strain BH072 isolated from a honey sample showed antifungal activity against mold. Based on morphological, biochemical, physiological tests, and analysis of 16S rDNA sequence, the strain was identified to be a new subspecies of Bacillus sp. It had a broad spectrum of antifungal activity against various mold, such as Aspergillus niger, Pythium, and Botrytis cinerea. Six pairs of antifungal genes primers were designed and synthesized, and ituA, hag, tasA genes were detected by PCR analysis. The remarkable antifungal activity could be associated with the co-production of these three peptides. One of them was purified by 30-40% ammonium sulfate precipitation, Sephadex G-75 gel filtration and anion exchange chromatography on D201 resin. The purified peptide was estimated to be 35.615 kDa and identified to be flagellin by micrOTOF-Q II. By using methanol extraction, another substance was isolated from fermentation liquor, and determined to be iturin with liquid chromatography-mass spectrometry (LC-MS) method. The third possible peptide encoded by tasA was not isolated in this study. The culture liquor displayed antifungal activity in a wide pH range (5.0-9.0) and at 40-100°C. The result of the present work suggested that Bacillus BH072 might be a bio-control bacterium of research value. PMID:23545354

  11. Koningiopisins A-H, Polyketides with Synergistic Antifungal Activities from the Endophytic Fungus Trichoderma koningiopsis.

    PubMed

    Liu, Kai; Yang, Yabin; Miao, Cui-Ping; Zheng, You-Kun; Chen, Jin-Lian; Chen, You-Wei; Xu, Li-Hua; Guang, Hui-Lin; Ding, Zhong-Tao; Zhao, Li-Xing

    2016-03-01

    Eight new fungal polyketides named koningiopisins A-H (1-8) and four previously known polyketides (9-12) were isolated from the endophytic fungus Trichoderma koningiopsis YIM PH 30002. Their structures were elucidated using extensive spectral data interpretation, and their antifungal and synergistic activities were also evaluated. Koningiopisin C (3) exhibited in vitro antifungal activity against the phytopathogenic fungus Plectosphaerella cucumerina with an MIC of 16 µg/mL. Although the antifungal activities of single compounds were not obvious, a mixture of six compounds (4-9) exhibited potent synergistic antifungal activity against P. cucumerina with an MIC of 16 µg/mL, and the antifungal activity of the mixture of any two compounds with a 1:1 ratio was better than that observed from the individual compound. The synergistic biological activity of the metabolites in YIM PH 30002 demonstrates the significant ecological function of the endophyte for its host plant, and provides additional insight into the search for and development of agents for biological control. PMID:26692458

  12. Synergy Between Polyvinylpyrrolidone-Coated Silver Nanoparticles and Azole Antifungal Against Drug-Resistant Candida albicans.

    PubMed

    Sun, Lingmei; Liao, Kai; Li, Yiping; Zhao, Lei; Liang, Sai; Guo, Dan; Hu, Jun; Wang, Dayong

    2016-03-01

    In the clinical practice, resistance of Candida albicans to antifungal agents has frequently emerged. Silver-nanoparticles (Ag-NPs) have been demonstrated to have the antifungal property. We investigated the potential for synergy between polyvinylpyrrolidone (PVP)-coated Ag-NPs and azole antifungal, such as fluconazole or voriconazole, against drug-resistant C. albicans strain CA10. When antifungal agent was examined alone, fluconazole and voriconazole did not kill drug-resistant C. albicans, and PVP-coated Ag-NPs had only the moderate killing ability. In contrast, the combinational treatment of PVP-coated Ag-NPs with fluconazole or voriconazole was effective in being against the drug-resistant C. albicans. After the combinational treatment, we detected the disruption of cell membrane integrity, the tendency of PVP-coated Ag-NPs to adhere to cell membrane, and the inhibition of budding process. Moreover, after the combinational treatment, the defects in ergosterol signaling and efflux pump functions were detected. Our results suggest that the combinational use of engineered nanomaterials (ENMs), such as PVP-coated Ag-NPs, with the conventional antifungal may be a viable strategy to combat drug-resistant fungal infection. PMID:27455637

  13. Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

    PubMed Central

    Lakshminarayanan, Rajamani; Sridhar, Radhakrishnan; Loh, Xian Jun; Nandhakumar, Muruganantham; Barathi, Veluchamy Amutha; Kalaipriya, Madhaiyan; Kwan, Jia Lin; Liu, Shou Ping; Beuerman, Roger Wilmer; Ramakrishna, Seeram

    2014-01-01

    Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole) electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes. The polyene-loaded fiber mats were noncytotoxic to primary human corneal and sclera fibroblasts. The reduction of toxicity with complete retention of activity of the polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the management of superficial skin infections. PMID:24920895

  14. Epidemiology and antifungal susceptibilities of yeasts causing vulvovaginitis in a teaching hospital.

    PubMed

    Gamarra, Soledad; Morano, Susana; Dudiuk, Catiana; Mancilla, Estefanía; Nardin, María Elena; de Los Angeles Méndez, Emilce; Garcia-Effron, Guillermo

    2014-10-01

    Vulvovaginal candidiasis is one of the most common mycosis. However, the information about antifungal susceptibilities of the yeasts causing this infection is scant. We studied 121 yeasts isolated from 118 patients with vulvovaginal candidiasis. The isolates were identified by phenotypic and molecular methods, including four phenotypic methods described to differentiate Candida albicans from C. dubliniensis. Antifungal susceptibility testing was performed according to CLSI documents M27A3 and M27S4 using the drugs available as treatment option in the hospital. Diabetes, any antibacterial and amoxicillin treatment were statistically linked with vulvovaginal candidiasis, while oral contraceptives were not considered a risk factor. Previous azole-based over-the-counter antifungal treatment was statistically associated with non-C.albicans yeasts infections. The most common isolated yeast species was C. albicans (85.2 %) followed by C. glabrata (5 %), Saccharomyces cerevisiae (3.3 %), and C. dubliniensis (2.5 %). Fluconazole- and itraconazole-reduced susceptibility was observed in ten and in only one C. albicans strains, respectively. All the C. glabrata isolates showed low fluconazole MICs. Clotrimazole showed excellent potency against all but seven isolates (three C. glabrata, two S. cerevisiae, one C. albicans and one Picchia anomala). Any of the strains showed nystatin reduced susceptibility. On the other hand, terbinafine was the less potent drug. Antifungal resistance is still a rare phenomenon supporting the use of azole antifungals as empirical treatment of vulvovaginal candidiasis. PMID:25005365

  15. INJECTABLE IN SITU CROSS-LINKING HYDROGELS FOR LOCAL ANTIFUNGAL THERAPY

    PubMed Central

    Hudson, Sarah; Langer, Robert; Fink, Gerald R.; Kohane, Daniel S.

    2009-01-01

    Invasive fungal infections can be devastating, particularly in immunocompromised patients, and difficult to treat with systemic drugs. Furthermore, systemic administration of those medications can have severe side effects. We have developed an injectable local antifungal treatment for direct administration into existing or potential sites of fungal infection. Amphotericin B (AmB), a hydrophobic, potent, and broad-spectrum antifungal agent, was rendered water-soluble by conjugation to a dextran-aldehyde polymer. The dextran-aldehyde-AmB conjugate retained antifungal efficacy against C. albicans. Mixing carboxymethylcellulose-hydrazide with dextran-aldehyde formed a gel that cross-linked in situ by formation of hydrazone bonds. The gel provided in vitro release of antifungal activity for 11 days, and contact with the gel killed Candida for three weeks. There was no apparent tissue toxicity in the murine peritoneum and the gel caused no adhesions. Gels produced by entrapment of a suspension of AmB in CMC-dextran without conjugation of drug to polymers did not release fungicidal activity, but did kill on contact. Injectable systems of these types, containing soluble or insoluble drug formulations, could be useful for treatment of local antifungal infections, with or without concurrent systemic therapy. PMID:19942285

  16. Purification and Molecular Identification of an Antifungal Peptide from the Hemolymph of Musca domestica (housefly)

    PubMed Central

    Fu, Ping; Wu, Jianwei; Guo, Guo

    2009-01-01

    Antibacterial and antifungal peptides found in houseflies (Musca domestica) in large number are indispensable components of its immune defense mechanism. In this study the anterior tip of the larvae of housefly was cut off with a pair of fine scissors and hemolymph was collected and exuded in an ice-cold test tube. From the hemolymph an antifungal substance was isolated by solid-phase extraction combined with reverse phase-high performance liquid chromotography (RP-HPLC) and named as Musca domestica antifungal peptide-1 (MAF-1). Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed its molecular weight was 17 kDa. UV absorption spectra revealed that this antifungal substance possessed the characteristics of protein peptides. Analysis by fingerprint-identification and tandem mass spectrometry suggested MAF-1 was an unknown protein. Edman degradation identified the sequence of 30 amino acids of its N-terminal which matched no peptide in the MASCOT search database, indicating MAF-1 was a novel insect antifungal peptide. Mass spectrometry showed the precise molecular weight of MAF-1 was 17203.384 Da. Its isoelectric point was acidic. PMID:19728925

  17. Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

    PubMed Central

    de Araújo, Rodrigo S. A.; Guerra, Felipe Q. S.; de O. Lima, Edeltrudes; de Simone, Carlos A.; Tavares, Josean F.; Scotti, Luciana; Scotti, Marcus T.; de Aquino, Thiago M.; de Moura, Ricardo O.; Mendonça, Francisco J. B.; Barbosa-Filho, José M.

    2013-01-01

    The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 μg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO2 and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity. PMID:23306152

  18. Expression in Escherichia coli, purification, refolding and antifungal activity of an osmotin from Solanum nigrum

    PubMed Central

    Campos, Magnólia de A; Silva, Marilia S; Magalhães, Cláudio P; Ribeiro, Simone G; Sarto, Rafael PD; Vieira, Eduardo A; Grossi de Sá, Maria F

    2008-01-01

    Background Heterologous protein expression in microorganisms may contribute to identify and demonstrate antifungal activity of novel proteins. The Solanum nigrum osmotin-like protein (SnOLP) gene encodes a member of pathogenesis-related (PR) proteins, from the PR-5 sub-group, the last comprising several proteins with different functions, including antifungal activity. Based on deduced amino acid sequence of SnOLP, computer modeling produced a tertiary structure which is indicative of antifungal activity. Results To validate the potential antifungal activity of SnOLP, a hexahistidine-tagged mature SnOLP form was overexpressed in Escherichia coli M15 strain carried out by a pQE30 vector construction. The urea solubilized His6-tagged mature SnOLP protein was affinity-purified by immobilized-metal (Ni2+) affinity column chromatography. As SnOLP requires the correct formation of eight disulfide bonds, not correctly formed in bacterial cells, we adapted an in vitro method to refold the E. coli expressed SnOLP by using reduced:oxidized gluthatione redox buffer. This method generated biologically active conformations of the recombinant mature SnOLP, which exerted antifungal action towards plant pathogenic fungi (Fusarium solani f. sp.glycines, Colletotrichum spp., Macrophomina phaseolina) and oomycete (Phytophthora nicotiana var. parasitica) under in vitro conditions. Conclusion Since SnOLP displays activity against economically important plant pathogenic fungi and oomycete, it represents a novel PR-5 protein with promising utility for biotechnological applications. PMID:18334031

  19. Effectiveness of Natural Antifungal Compounds in Controlling Infection by Grapevine Trunk Disease Pathogens through Pruning Wounds

    PubMed Central

    Cobos, Rebeca; Mateos, Rosa María; Álvarez-Pérez, José Manuel; Olego, Miguel Angel; Sevillano, Silvia; González-García, Sandra; Garzón-Jimeno, Enrique

    2015-01-01

    Grapevine trunk fungal pathogens, such as Diplodia seriata and Phaeomoniella chlamydospora, can infect plants through pruning wounds. They cause grapevine trunk diseases and are involved in grapevine decline. Accordingly, the protection of pruning wounds is crucial for the management of grapevine trunk diseases. The efficacy of different natural antifungals in inhibiting the growth of several fungi causing grapevine trunk diseases was evaluated in vitro. The fungi showing greater in vitro efficacy were tested on autoclaved grape wood assays against D. seriata and P. chlamydospora. Based on results from these assays, chitosan oligosaccharide, vanillin, and garlic extract were selected for further evaluation on pruning wounds inoculated with D. seriata and P. chlamydospora in field trials. A significant decrease in plant mortality was observed after 2 years of growth in the plants treated with the different natural antifungals compared to the mortality rate observed in infected plants that were not treated with antifungals. Also, the infection rate for the inoculated pathogens was significantly reduced in plants treated with the selected natural antifungals. Therefore, natural antifungals represent a promising alternative for disease control and could provide significant economic benefits for the grape-growing industry. PMID:26162882

  20. Characterisation of the Candida albicans Phosphopantetheinyl Transferase Ppt2 as a Potential Antifungal Drug Target

    PubMed Central

    Dobb, Katharine S.; Kaye, Sarah J.; Beckmann, Nicola; Thain, John L.; Stateva, Lubomira; Birch, Mike; Oliver, Jason D.

    2015-01-01

    Antifungal drugs acting via new mechanisms of action are urgently needed to combat the increasing numbers of severe fungal infections caused by pathogens such as Candida albicans. The phosphopantetheinyl transferase of Aspergillus fumigatus, encoded by the essential gene pptB, has previously been identified as a potential antifungal target. This study investigated the function of its orthologue in C. albicans, PPT2/C1_09480W by placing one allele under the control of the regulatable MET3 promoter, and deleting the remaining allele. The phenotypes of this conditional null mutant showed that, as in A. fumigatus, the gene PPT2 is essential for growth in C. albicans, thus fulfilling one aspect of an efficient antifungal target. The catalytic activity of Ppt2 as a phosphopantetheinyl transferase and the acyl carrier protein Acp1 as a substrate were demonstrated in a fluorescence transfer assay, using recombinant Ppt2 and Acp1 produced and purified from E.coli. A fluorescence polarisation assay amenable to high-throughput screening was also developed. Therefore we have identified Ppt2 as a broad-spectrum novel antifungal target and developed tools to identify inhibitors as potentially new antifungal compounds. PMID:26606674

  1. Heat shock protein 90 (Hsp90): A novel antifungal target against Aspergillus fumigatus.

    PubMed

    Lamoth, Frédéric; Juvvadi, Praveen R; Steinbach, William J

    2016-01-01

    Invasive aspergillosis is a life-threatening and difficult to treat infection in immunosuppressed patients. The efficacy of current anti-Aspergillus therapies, targeting the cell wall or membrane, is limited by toxicity (polyenes), fungistatic activity and some level of basal resistance (echinocandins), or the emergence of acquired resistance (triazoles). The heat shock protein 90 (Hsp90) is a conserved molecular chaperone involved in the rapid development of antifungal resistance in the yeast Candida albicans. Few studies have addressed its role in filamentous fungi such as Aspergillus fumigatus, in which mechanisms of resistance may differ substantially. Hsp90 is at the center of a complex network involving calcineurin, lysine deacetylases (KDAC) and other client proteins, which orchestrate compensatory repair mechanisms of the cell wall in response to the stress induced by antifungals. In A. fumigatus, Hsp90 is a trigger for resistance to high concentrations of caspofungin, known as the paradoxical effect. Disrupting Hsp90 circuitry by different means (Hsp90 inhibitors, KDAC inhibitors and anti-calcineurin drugs) potentiates the antifungal activity of caspofungin, thus representing a promising novel antifungal approach. This review will discuss the specific features of A. fumigatus Hsp90 and the potential for antifungal strategies of invasive aspergillosis targeting this essential chaperone. PMID:25243616

  2. Effectiveness of Natural Antifungal Compounds in Controlling Infection by Grapevine Trunk Disease Pathogens through Pruning Wounds.

    PubMed

    Cobos, Rebeca; Mateos, Rosa María; Álvarez-Pérez, José Manuel; Olego, Miguel Angel; Sevillano, Silvia; González-García, Sandra; Garzón-Jimeno, Enrique; Coque, Juan José R

    2015-09-01

    Grapevine trunk fungal pathogens, such as Diplodia seriata and Phaeomoniella chlamydospora, can infect plants through pruning wounds. They cause grapevine trunk diseases and are involved in grapevine decline. Accordingly, the protection of pruning wounds is crucial for the management of grapevine trunk diseases. The efficacy of different natural antifungals in inhibiting the growth of several fungi causing grapevine trunk diseases was evaluated in vitro. The fungi showing greater in vitro efficacy were tested on autoclaved grape wood assays against D. seriata and P. chlamydospora. Based on results from these assays, chitosan oligosaccharide, vanillin, and garlic extract were selected for further evaluation on pruning wounds inoculated with D. seriata and P. chlamydospora in field trials. A significant decrease in plant mortality was observed after 2 years of growth in the plants treated with the different natural antifungals compared to the mortality rate observed in infected plants that were not treated with antifungals. Also, the infection rate for the inoculated pathogens was significantly reduced in plants treated with the selected natural antifungals. Therefore, natural antifungals represent a promising alternative for disease control and could provide significant economic benefits for the grape-growing industry. PMID:26162882

  3. Comparison of in vitro antifungal activities of topical antimycotics launched in 1990s in Japan.

    PubMed

    Nimura, K; Niwano, Y; Ishiduka, S; Fukumoto, R

    2001-08-01

    In vitro anti-dermatophyte, anti-Candida albicans and anti-Malassezia furfur activities of amorolfine hydrochloride (AMF), terbinafine hydrochloride (TBF), butenafine hydrochloride (BTF), neticonazole hydrochloride (NCZ) and ketoconazole (KCZ), all of which were introduced for the treatment of dermatomycoses in the 1990s in Japan, were compared. Although all of the test drugs are classified as an ergosterol biosynthesis inhibitor, the antifungal properties were found to be different. TBF and BTF exerted extremely potent antifungal activity against Trichophyton spp. but not against C. albicans and M. furfur, whilst KCZ and NCZ showed potent antifungal activity against C. albicans and M. furfur rather than Trichophyton spp. AMF exhibited potent antifungal activity against all of the fungal species tested. Fungicidal activities of these antifungal agents against T. rubrum were determined by using neutral red staining. The fungicidal potentialities correlated with those obtained in the in vitro susceptibility test as determined by MICs against dermatophytes. TBF, BTF and AMF exerted more potent fungicidal action than NCZ and KCZ. PMID:11516941

  4. Antifungal effects of volatile compounds from black zira (Bunium persicum) and other spices and herbs.

    PubMed

    Sekine, Takayuki; Sugano, Mami; Majid, Azizi; Fujii, Yoshiharu

    2007-11-01

    The dish pack method, which measures growth inhibition or promotion effects of volatile compounds on germinating seeds, was applied to measure the antifungal effects of 52 dried samples of spices and herbs against a soil-borne phytopathogenic fungus, Fusarium oxysporum. Black zira showed the strongest effect, followed by cumin and cardamom. Headspace sampling and gas chromatography-mass spectrometry analysis of black zira identified seven volatile compounds, gamma-terpinene, limonene, p-cymene, beta-pinene, alpha-pinene, cuminaldehyde, and myrcene. Among these, cuminaldehyde and p-cymene showed the strongest antifungal activities against F. oxysporum, suggesting roles in the antifungal activity of black zira. The same compounds also showed antifungal activities against another soil-borne phytopathogenic fungus, Verticillium dahliae, and foliar phytopathogenic fungi, Botrytis cinerea and Alternaria mali. The total activity calculated from the concentration of cuminaldehyde contained in black zira and its EC(50) against F. oxysporum demonstrated that cuminaldehyde is the main antifungal compound detected in black zira. PMID:17932718

  5. Laccase Catalyzed Synthesis of Iodinated Phenolic Compounds with Antifungal Activity

    PubMed Central

    Ihssen, Julian; Schubert, Mark; Thöny-Meyer, Linda; Richter, Michael

    2014-01-01

    Iodine is a well known antimicrobial compound. Laccase, an oxidoreductase which couples the one electron oxidation of diverse phenolic and non-phenolic substrates to the reduction of oxygen to water, is capable of oxidizing unreactive iodide to reactive iodine. We have shown previously that laccase-iodide treatment of spruce wood results in a wash-out resistant antimicrobial surface. In this study, we investigated whether phenolic compounds such as vanillin, which resembles sub-structures of softwood lignin, can be directly iodinated by reacting with laccase and iodide, resulting in compounds with antifungal activity. HPLC-MS analysis showed that vanillin was converted to iodovanillin by laccase catalysis at an excess of potassium iodide. No conversion of vanillin occurred in the absence of enzyme. The addition of redox mediators in catalytic concentrations increased the rate of iodide oxidation ten-fold and the yield of iodovanillin by 50%. Iodinated phenolic products were also detected when o-vanillin, ethyl vanillin, acetovanillone and methyl vanillate were incubated with laccase and iodide. At an increased educt concentration of 0.1 M an almost one to one molar ratio of iodide to vanillin could be used without compromising conversion rate, and the insoluble iodovanillin product could be recovered by simple centrifugation. The novel enzymatic synthesis procedure fulfills key criteria of green chemistry. Biocatalytically produced iodovanillin and iodo-ethyl vanillin had significant growth inhibitory effects on several wood degrading fungal species. For Trametes versicolor, a species causing white rot of wood, almost complete growth inhibition and a partial biocidal effect was observed on agar plates. Enzymatic tests indicated that the iodinated compounds acted as enzyme responsive, antimicrobial materials. PMID:24594755

  6. Laccase catalyzed synthesis of iodinated phenolic compounds with antifungal activity.

    PubMed

    Ihssen, Julian; Schubert, Mark; Thöny-Meyer, Linda; Richter, Michael

    2014-01-01

    Iodine is a well known antimicrobial compound. Laccase, an oxidoreductase which couples the one electron oxidation of diverse phenolic and non-phenolic substrates to the reduction of oxygen to water, is capable of oxidizing unreactive iodide to reactive iodine. We have shown previously that laccase-iodide treatment of spruce wood results in a wash-out resistant antimicrobial surface. In this study, we investigated whether phenolic compounds such as vanillin, which resembles sub-structures of softwood lignin, can be directly iodinated by reacting with laccase and iodide, resulting in compounds with antifungal activity. HPLC-MS analysis showed that vanillin was converted to iodovanillin by laccase catalysis at an excess of potassium iodide. No conversion of vanillin occurred in the absence of enzyme. The addition of redox mediators in catalytic concentrations increased the rate of iodide oxidation ten-fold and the yield of iodovanillin by 50%. Iodinated phenolic products were also detected when o-vanillin, ethyl vanillin, acetovanillone and methyl vanillate were incubated with laccase and iodide. At an increased educt concentration of 0.1 M an almost one to one molar ratio of iodide to vanillin could be used without compromising conversion rate, and the insoluble iodovanillin product could be recovered by simple centrifugation. The novel enzymatic synthesis procedure fulfills key criteria of green chemistry. Biocatalytically produced iodovanillin and iodo-ethyl vanillin had significant growth inhibitory effects on several wood degrading fungal species. For Trametes versicolor, a species causing white rot of wood, almost complete growth inhibition and a partial biocidal effect was observed on agar plates. Enzymatic tests indicated that the iodinated compounds acted as enzyme responsive, antimicrobial materials. PMID:24594755

  7. Biogenic silver nanoparticles: efficient and effective antifungal agents

    NASA Astrophysics Data System (ADS)

    Netala, Vasudeva Reddy; Kotakadi, Venkata Subbaiah; Domdi, Latha; Gaddam, Susmila Aparna; Bobbu, Pushpalatha; Venkata, Sucharitha K.; Ghosh, Sukhendu Bikash; Tartte, Vijaya

    2016-04-01

    Biogenic synthesis of silver nanoparticles (AgNPs) by exploiting various plant materials is an emerging field and considered green nanotechnology as it involves simple, cost effective and ecofriendly procedure. In the present study AgNPs were successfully synthesized using aqueous callus extract of Gymnema sylvestre. The aqueous callus extract treated with 1nM silver nitrate solution resulted in the formation of AgNPs and the surface plasmon resonance (SPR) of the formed AgNPs showed a peak at 437 nm in the UV Visible spectrum. The synthesized AgNPs were characterized using Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM), and X-ray diffraction spectroscopy (XRD). FTIR spectra showed the peaks at 3333, 2928, 2361, 1600, 1357 and 1028 cm-1 which revealed the role of different functional groups possibly involved in the synthesis and stabilization of AgNPs. TEM micrograph clearly revealed the size of the AgNPs to be in the range of 3-30 nm with spherical shape and poly-dispersed nature; it is further confirmed by Particle size analysis that the stability of AgNPs is due its high negative Zeta potential (-36.1 mV). XRD pattern revealed the crystal nature of the AgNPs by showing the braggs peaks corresponding to (111), (200), (220) and (311) planes of face-centered cubic crystal phase of silver. Selected area electron diffraction pattern showed diffraction rings and confirmed the crystalline nature of synthesized AgNPs. The synthesized AgNPs exhibited effective antifungal activity against Candida albicans, Candida nonalbicans and Candida tropicalis.

  8. Evolution of Chemical Diversity in Echinocandin Lipopeptide Antifungal Metabolites

    PubMed Central

    Yue, Qun; Chen, Li; Zhang, Xiaoling; Li, Kuan; Sun, Jingzu; Liu, Xingzhong

    2015-01-01

    The echinocandins are a class of antifungal drugs that includes caspofungin, micafungin, and anidulafungin. Gene clusters encoding most of the structural complexity of the echinocandins provided a framework for hypotheses about the evolutionary history and chemical logic of echinocandin biosynthesis. Gene orthologs among echinocandin-producing fungi were identified. Pathway genes, including the nonribosomal peptide synthetases (NRPSs), were analyzed phylogenetically to address the hypothesis that these pathways represent descent from a common ancestor. The clusters share cooperative gene contents and linkages among the different strains. Individual pathway genes analyzed in the context of similar genes formed unique echinocandin-exclusive phylogenetic lineages. The echinocandin NRPSs, along with the NRPS from the inp gene cluster in Aspergillus nidulans and its orthologs, comprise a novel lineage among fungal NRPSs. NRPS adenylation domains from different species exhibited a one-to-one correspondence between modules and amino acid specificity that is consistent with models of tandem duplication and subfunctionalization. Pathway gene trees and Ascomycota phylogenies are congruent and consistent with the hypothesis that the echinocandin gene clusters have a common origin. The disjunct Eurotiomycete-Leotiomycete distribution appears to be consistent with a scenario of vertical descent accompanied by incomplete lineage sorting and loss of the clusters from most lineages of the Ascomycota. We present evidence for a single evolutionary origin of the echinocandin family of gene clusters and a progression of structural diversification in two fungal classes that diverged approximately 290 to 390 million years ago. Lineage-specific gene cluster evolution driven by selection of new chemotypes contributed to diversification of the molecular functionalities. PMID:26024901

  9. Acyl secoiridoids and antifungal constituents from Gentiana macrophylla.

    PubMed

    Tan, R X; Wolfender, J L; Zhang, L X; Ma, W G; Fuzzati, N; Marston, A; Hostettmann, K

    1996-07-01

    LC-UV-mass spectrometry and bioassay co-directed fractionation of an aqueous acetone extract of the roots of Gentiana macrophylla gave three new chromene derivatives and two novel and six known secoiridoids, along with kurarinone, kushenol I, beta-sitosterol, stigmasterol, daucosterol, beta-sitosterol-3-O-gentiobioside, alpha-amyrin, oleanolic acid, isovitexin, gentiobiose and methyl 2-hydroxy-3-(1-beta-D-glucopyranosyl)oxybenzoate. The structures of the new products were established from spectral and chemical evidence as 2-methoxyanofinic acid and macrophyllosides A-D. The six known secoiridoids were gentiopicroside, sweroside, 6'-O-beta-D-glucosylgentiopicroside, 6'-O-beta-D-glucosylsweroside, trifloroside and rindoside. The new acid (2-methoxyanofinic acid), its methyl ester, kurarinone and kushenol I were shown to be active against the plant pathogenic fungus Cladosporium cucumerinum. The methyl ester and kurarinone inhibited also the growth of the human pathogenic yeast Candida albicans. Structure-activity relationships were studied. Thus, addition of a methoxyl group to the benzene nucleus of anofinic acid (2,2-dimethyl-2H-1-benzopyran-6-carboxylic acid) increased the antifungal activity remarkably whereas glycosylation at the carboxylic moiety was found to remove the activity. Esterification of the new acid induced its activity against C. albicans, but decreased its growth inhibition properties against C. cucumerinum. Hydroxylation of kurarinone at the 3 beta-position removed its activity against C. albicans and decreased the inhibition of C. cucumerinum. In addition, the chemotaxonomic significance of the identified constituents is discussed. PMID:9397205

  10. Antifungal drug resistance evokedvia RNAi-dependent epimutations

    PubMed Central

    Calo, Silvia; Shertz-Wall, Cecelia; Lee, Soo Chan; Bastidas, Robert J.; Nicolás, Francisco E.; Granek, Joshua A.; Mieczkowski, Piotr; Torres-Martinez, Santiago; Ruiz-Vazquez, Rosa M.; Cardenas, Maria E.; Heitman, Joseph

    2014-01-01

    Microorganisms evolve via mechanisms spanning sexual/parasexual reproduction, mutators, aneuploidy, Hsp90, and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show the human fungal pathogen Mucor circinelloides develops spontaneous resistance to the antifungal drug FK506 (tacrolimus) via two distinct mechanisms. One involves Mendelian mutations that confer stable drug resistance; the other occurs via an epigenetic RNA interference (RNAi)-mediated pathway resulting in unstable drug resistance. The peptidyl-prolyl isomerase FKBP12 interacts with FK506 forming a complex that inhibits the protein phosphatase calcineurin1. Calcineurin inhibition by FK506 blocks M. circinelloides transition to hyphae and enforces yeast growth2. Mutations in the fkbA gene encoding FKBP12 or the calcineurin cnbR or cnaA genes confer FK506 resistance (FK506R) and restore hyphal growth. In parallel, RNAi is spontaneously triggered to silence the FKBP12 fkbA gene, giving rise to drug-resistant epimutants. FK506R epimutants readily reverted to the drug-sensitive wild-type (WT) phenotype when grown without drug. The establishment of these epimutants is accompanied by generation of abundant fkbA small RNA (sRNA) and requires the RNAi pathway as well as other factors that constrain or reverse the epimutant state. Silencing involves generation of a double-stranded RNA (dsRNA) trigger intermediate from the fkbA mature mRNA to produce antisense fkbA RNA. This study uncovers a novel epigenetic RNAi-based epimutation mechanism controlling phenotypic plasticity, with possible implications for antimicrobial drug resistance and RNAi-regulatory mechanisms in fungi and other eukaryotes. PMID:25079329

  11. Components of the calcium-calcineurin signaling pathway in fungal cells and their potential as antifungal targets.

    PubMed

    Liu, Shuyuan; Hou, Yinglong; Liu, Weiguo; Lu, Chunyan; Wang, Weixin; Sun, Shujuan

    2015-04-01

    In recent years, the emergence of fungal resistance has become frequent, partly due to the widespread clinical use of fluconazole, which is minimally toxic and effective in the prevention and treatment of Candida albicans infections. The limited selection of antifungal drugs for clinical fungal infection therapy has prompted us to search for new antifungal drug targets. Calcium, which acts as the second messenger in both mammals and fungi, plays a direct role in controlling the expression patterns of its signaling systems and has important roles in cell survival. In addition, calcium and some of the components, mainly calcineurin, in the fungal calcium signaling pathway mediate fungal resistance to antifungal drugs. Therefore, an overview of the components of the fungal calcium-calcineurin signaling network and their potential roles as antifungal targets is urgently needed. The calcium-calcineurin signaling pathway consists of various channels, transporters, pumps, and other proteins or enzymes. Many transcriptional profiles have indicated that mutant strains that lack some of these components are sensitized to fluconazole or other antifungal drugs. In addition, many researchers have identified efficient compounds that exhibit antifungal activity by themselves or in combination with antifungal drugs by targeting some of the components in the fungal calcium-calcineurin signaling pathway. This targeting disrupts Ca(2+) homeostasis, which suggests that this pathway contains potential targets for the development of new antifungal drugs. PMID:25636321

  12. Components of the Calcium-Calcineurin Signaling Pathway in Fungal Cells and Their Potential as Antifungal Targets

    PubMed Central

    Liu, Shuyuan; Hou, Yinglong; Liu, Weiguo; Lu, Chunyan; Wang, Weixin

    2015-01-01

    In recent years, the emergence of fungal resistance has become frequent, partly due to the widespread clinical use of fluconazole, which is minimally toxic and effective in the prevention and treatment of Candida albicans infections. The limited selection of antifungal drugs for clinical fungal infection therapy has prompted us to search for new antifungal drug targets. Calcium, which acts as the second messenger in both mammals and fungi, plays a direct role in controlling the expression patterns of its signaling systems and has important roles in cell survival. In addition, calcium and some of the components, mainly calcineurin, in the fungal calcium signaling pathway mediate fungal resistance to antifungal drugs. Therefore, an overview of the components of the fungal calcium-calcineurin signaling network and their potential roles as antifungal targets is urgently needed. The calcium-calcineurin signaling pathway consists of various channels, transporters, pumps, and other proteins or enzymes. Many transcriptional profiles have indicated that mutant strains that lack some of these components are sensitized to fluconazole or other antifungal drugs. In addition, many researchers have identified efficient compounds that exhibit antifungal activity by themselves or in combination with antifungal drugs by targeting some of the components in the fungal calcium-calcineurin signaling pathway. This targeting disrupts Ca2+ homeostasis, which suggests that this pathway contains potential targets for the development of new antifungal drugs. PMID:25636321

  13. Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several benzoic acid analogs showed antifungal activity against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis. Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids increased by addition of a methyl, methoxyl...

  14. Design, synthesis and molecular docking studies of novel triazole as antifungal agent.

    PubMed

    Chai, Xiaoyun; Zhang, Jun; Cao, Yongbing; Zou, Yan; Wu, Qiuye; Zhang, Dazhi; Jiang, Yuanying; Sun, Qingyan

    2011-07-01

    In order to meet the urgent need for novel antifungal agents with improved activity and broader spectrum, a series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substituted trifluoromethyl phenyl)-piperazin-1-yl]-propan-2-ols were designed, synthesized and evaluated as antifungal agents. The MIC(80) values indicate that the compounds 7a-7q, 8a-8d showed higher antifungal activities against Candida albicans than 5a-5i, 6a-6j. Moreover, the molecular model for the binding between compound 5a, 7a and the active site of CACYP51 was provided based on the computational docking results, and the structure-activity relationship was analyzed. PMID:21531485

  15. Chemical characterization and antifungal activity of essential oil of capitula from wild Indian Tagetes patula L.

    PubMed

    Romagnoli, C; Bruni, R; Andreotti, E; Rai, M K; Vicentini, C B; Mares, D

    2005-04-01

    The essential oil extracted by steam distillation from the capitula of Indian Tagetes patula, Asteraceae, was evaluated for its antifungal properties and analyzed by gas chromatography and gas chromatography-mass spectrometry. Thirty compounds were identified, representing 89.1% of the total detected. The main components were piperitone (24.74%), piperitenone (22.93%), terpinolene (7.8%), dihydro tagetone (4.91%), cis-tagetone (4.62%), limonene (4.52%), and allo-ocimene (3.66%). The oil exerted a good antifungal activity against two phytopathogenic fungi, Botrytis cinerea and Penicillium digitatum, providing complete growth inhibition at 10 microl/ml and 1.25 microl/ml, respectively. The contribution of the two main compounds, piperitone and piperitenone, to the antifungal efficacy was also evaluated and ultrastructural modifications in mycelia were observed via electron microscopy, evidencing large alterations in hyphal morphology and a multisite mechanism of action. PMID:15868213

  16. Alocasin, an anti-fungal protein from rhizomes of the giant taro Alocasia macrorrhiza.

    PubMed

    Wang, H X; Ng, T B

    2003-03-01

    An anti-fungal protein designated alocasin was isolated from the rhizomes of the giant taro Alocasia macrorrhiza. The isolation protocol involved ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose, ion exchange chromatography on sulfopropyl (SP)-Sepharose, and gel filtration on Superdex 75. Alocasin, which was unadsorbed on DEAE-cellulose and SP-Sepharose, possessed the N-terminal sequence APEGEV, which exhibited some similarity to that of the miraculin-like anti-fungal protein from Pisum sativum legumes. It demonstrated a molecular mass of 11kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration, and displayed anti-fungal activity against Botrytis cinerea. Alocasin reduced the activity of HIV-1 reverse transcriptase. It exhibited weak hemagglutinating activity, only at a concentration of 1mg/ml. PMID:12651101

  17. Potential of selected lactic acid bacteria to produce food compatible antifungal metabolites.

    PubMed

    De Muynck, Cassandra; Leroy, Annelies I J; De Maeseneire, Sofie; Arnaut, Filip; Soetaert, Wim; Vandamme, Erick J

    2004-01-01

    The aim of this study was to assess the potential of lactic acid bacteria to inhibit the outgrowth of some common food-spoiling fungi. Culture supernatants of 17 Lactic acid bacterial strains as well as of three commercial probiotic cultures were evaluated for antifungal activity using an agar-diffusion method. The method parameters were chosen in order to reveal compounds for potential use in food (bio)preservation. Thirteen strains showed antifungal activity of which five strains were very promising: Lactobacillus acidophilus LMG 9433, L. amylovorus DSM 20532, L. brevis LMG 6906, L. coryniformis subsp. coryniformis LMG 9196 and L. plantarum LMG 6907. Four of these five strains were further examined; it was found that the produced antifungal metabolites were pH-dependent. The exact chemical nature of these substances has not been revealed yet. PMID:15646380

  18. Antifungal dibenzofuran bis(bibenzyl)s from the liverwort Asterella angusta.

    PubMed

    Qu, Jianbo; Xie, Chunfeng; Guo, Huaifang; Yu, Wentao; Lou, Hongxiang

    2007-07-01

    Bioactivity-guided separation of an antifungal extract from the liverwort Asterella angusta afforded four bis(bibenzyl)s, asterelin A (1), asterelin B (2), 11-O-demethyl marchantin I (3), and dihydroptychantol A (4), together with six known ones. Their structures were established by extensive spectroscopic analysis (1D and 2D-NMR, MS), and that of 2 was confirmed by X-ray crystallographic diffraction analysis. Compounds 1 and 2 are the first examples of dibenzofuran bis(bibenzyl)s. The antifungal activity of the isolated bis(bibenzyl)s against the common clinical pathogenic fungus Candida albicans was evaluated using both the thin-layer chromatography bioautographic assay and the broth microdilution method. They showed moderate antifungal activities with minimal inhibitory concentration (MIC) values ranging from 16 microg/ml to 512 microg/ml. PMID:17570447

  19. Candida Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents

    PubMed Central

    Spampinato, Claudia

    2013-01-01

    The genus Candida includes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised. Candida infections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genus Candida and yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment of Candida infections is also provided. PMID:23878798

  20. A novel antifungal protein with lysozyme-like activity from seeds of Clitoria ternatea.

    PubMed

    K, Ajesh; K, Sreejith

    2014-06-01

    An antifungal protein with a molecular mass of 14.3 kDa was isolated from the seeds of butterfly pea (Clitoria ternatea) and designated as Ct protein. The antifungal protein was purified using different methods including ammonium sulphate precipitation, ion exchange chromatography on DEAE-cellulose and gel filtration on Sephadex G-50 column. Ct protein formed a single colourless rod-shaped crystal by hanging drop method after 7 days of sample loading. The protein showed lytic activity against Micrococcus luteus and broad-spectrum, fungicidal activity, particularly against the most clinically relevant yeasts, such as Cryptococcus neoformans, Cryptococcus albidus, Cryptococcus laurentii, Candida albicans and Candida parapsilosis. It also exerted an inhibitory activity on mycelial growth in several mould species including Curvularia sp., Alternaria sp., Cladosporium sp., Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Rhizopus sp., and Sclerotium sp. The present study adds to the literature on novel seed proteins with antifungal activity. PMID:24691882

  1. Synthesis and Antifungal Activity of Functionalized 2,3-Spirostane Isomers

    PubMed Central

    Upadhyay, Sunil Kumar; Creech, Clinton C.; Bowdy, Katharine L.; Stevens, Edwin D.; Jursic, Branko S.; Neumann, Donna M.

    2011-01-01

    Invasive fungal infections are a major complication for individuals with compromised immune systems. One of the most significant challenges in the treatment of invasive fungal infections is the increased resistance of many organisms to widely used antifungals, making the development of novel antifungal agents essential. Many naturally occurring products have been found to be effective antimicrobial agents. In particular, saponins with spirostane glycosidic moieties- isolated from plant or marine species- have been shown to possess a range of antimicrobial properties. In this report, we outline a novel approach to the synthesis of a number of functionalized spirostane molecules that can be further used as building blocks for novel spirostane-linked glycosides and present results from the in vitro screenings of the antifungal potential of each derivative against four fungal species, including Candida albicans, Cryptococcus neoformans, Candida glabrata, and the filamentous fungus Aspergillus fumigatus. PMID:21489791

  2. Synthesis and characterization of dithiocarbamate chitosan derivatives with enhanced antifungal activity.

    PubMed

    Qin, Yukun; Liu, Song; Xing, Ronge; Yu, Huahua; Li, Kecheng; Meng, Xiangtao; Li, Rongfeng; Li, Pengcheng

    2012-06-20

    In this study, ammonium dithiocarbamate chitosan (ADTCCS) and triethylene diamine dithiocarbamate chitosan (TEDADTCCS) derivatives were obtained respectively by mixing chitosan with carbon disulfide and ammonia (triethylenediamine). Their structures were confirmed by FT-IR, 1H NMR, XRD, DSC, SEM, and elemental analysis. Antifungal properties of them against the plant pathogenic fungi Fusarium oxysporum and Alternaria porri were investigated at concentrations ranged from 31.25 to 500 mg/L. The dithiocarbamate chitosan derivatives had enhanced antifungal activity compared with chitosan. Particularly, they showed obvious inhibitory effect on Fusarium oxysporum. At 500 mg/L, TEDADTCCS inhibited growth of F. oxysporum at 60.4%, stronger than polyoxin and triadimefon whose antifungal indexes were found to be 25.3% and 37.7%. The chitosan derivatives described here deserve further study for use in crop protection. PMID:24750734

  3. Isolation and antifungal activity of kakuol, a propiophenone derivative from Asarum sieboldii rhizome.

    PubMed

    Lee, Jung Yeop; Moon, Surk Sik; Hwang, Byung Kook

    2005-08-01

    An antifungal substance active against Colletotrichum orbiculare (Berk & Mont) Arx was isolated from the methanol extracts of Asarum sieboldii (Miq) Maek rhizomes. High-resolution MS, NMR and UV spectral data confirmed that the antifungal substance is kakuol, 2-hydroxy-4,5-methylenedioxypropiophenone. Colletotrichum orbiculare was most sensitive to kakuol, with MIC of 10 microg ml(-1). Kakuol also completely inhibited the mycelial growth of Botrytis cinerea Pers ex Fr and Cladosporium cucumerinum Ellis & Arthur at 50 microg ml(-1) and 30 microg ml(-1), respectively. However, no antimicrobial activity was found against yeast and bacteria even at 100 microg ml(-1). Kakuol exhibited a protective activity against the development of anthracnose disease on cucumber plants. The control efficacy of kakuol against the anthracnose disease was in general somewhat less than that of the commercial fungicide chlorothalonil. This is the first report to demonstrate in vitro and in vivo antifungal activity of kakuol against C. orbiculare infection. PMID:15846774

  4. Photoactive extracts from Thevetia peruviana with antifungal properties against Cladosporium cucumerinum.

    PubMed

    Gata-Gonçalves, Lígia; Nogueira, J M F; Matos, Olívia; Bruno de Sousa, Raúl

    2003-04-01

    Seeds of Thevetia peruviana were screened for their antifungal photoactivity. Extracts obtained either with n-hexane or dichloromethane were fractionated by column chromatography and further analysed by thin-layer chromatography. All seed extracts and fractions were tested for inhibition of the fungus Cladosporium cucumerinum for the evaluation of photoactive inhibitory effects. Antifungal light-dependent activity was observed for some of the fractions and both crude extracts. The most photoactive fraction was analysed by capillary gas chromatography with mass spectrometry in order to identify its constituents. Two major groups of compounds were identified, terpenes and fatty acids and derivatives. Pulegone, linoleic acid and palmitic acid were the major compounds. Terpenes seem to be the major substances with antifungal photoactivity. PMID:12745247

  5. Synthesis and antifungal activity of 2-hydroxy-4,5-methylenedioxyaryl ketones as analogues of kakuol.

    PubMed

    Musso, Loana; Dallavalle, Sabrina; Merlini, Lucio; Farina, Gandolfina

    2010-04-01

    In a study aiming to determine the structural elements essential to the antifungal activity of kakuol, we synthesized a series of 2-hydroxy-4,5-methylenedioxyaryl ketones, and we assayed their in vitro antifungal activity. The most sensitive target organisms to the action of these class of compounds were Phytophthora infestans, Phytium ultimum, Cercospora beticola, Cladosporium cucumerinum, and Rhizoctonia solani. Most of the analogs showed a remarkable in vitro activity, and some of them appeared significantly more effective than the natural product. The biological activity was mainly affected by introducing structural modification on the carbonyl moiety of the natural-product molecule. In particular, compound 5a, bearing a C=C bond conjugated to the C=O group, was found active with a MIC value of 10 microg ml(-1) against Cladosporium cucumerinum. The results suggest that 2-hydroxy-4,5-methylenedioxyaryl ketones can be considered promising candidates in the development of new antifungal compounds. PMID:20397224

  6. Antifungal Effects of Silver Nanoparticles (AgNPs) against Various Plant Pathogenic Fungi

    PubMed Central

    Kim, Sang Woo; Jung, Jin Hee; Lamsal, Kabir; Kim, Yun Seok; Min, Ji Seon

    2012-01-01

    This research is concerned with the fungicidal properties of nano-size silver colloidal solution used as an agent for antifungal treatment of various plant pathogens. We used WA-CV-WA13B, WA-AT-WB13R, and WA-PR-WB13R silver nanoparticles (AgNPs) at concentrations of 10, 25, 50, and 100 ppm. Eighteen different plant pathogenic fungi were treated with these AgNPs on potato dextrose agar (PDA), malt extract agar, and corn meal agar plates. We calculated fungal inhibition in order to evaluate the antifungal efficacy of silver nanoparticles against pathogens. The results indicated that AgNPs possess antifungal properties against these plant pathogens at various levels. Treatment with WA-CV-WB13R AgNPs resulted in maximum inhibition of most fungi. Results also showed that the most significant inhibition of plant pathogenic fungi was observed on PDA and 100 ppm of AgNPs. PMID:22783135

  7. Vulgarinin, a broad-spectrum antifungal peptide from haricot beans (Phaseolus vulgaris).

    PubMed

    Wong, Jack Ho; Ng, Tzi Bun

    2005-08-01

    From the seeds of haricot beans (Phaseolus vulgaris), an antifungal peptide with a molecular mass around 7 kDa was purified by using a simple protocol consisting of affinity chromatography on Affi-gel blue gel and gel filtration on Superdex 75. This peptide named vulgarinin manifested an antifungal activity toward fungal species such as Fusarium oxysporum, Mycosphaerella arachidicola, Physalospora piricola and Botrytis cinerea, and an antibacterial action on Mycobacterium phlei, Bacillus megaterium, Bacillus subtilis and Proteus vulgaris. It also inhibited proliferation in leukemia cell lines L1210 and M1 and breast cancer cell line MCF-7. This peptide could reduce the activity of HIV-1 reverse transcriptase and inhibited translation in a cell-free rabbit reticulocyte lysate system. Its antifungal activity was retained after incubation with trypsin. PMID:15896669

  8. Halogenated benzoate derivatives of altholactone with improved anti-fungal activity.

    PubMed

    Euanorasetr, Jirayut; Junhom, Mayura; Tantimavanich, Srisurang; Vorasin, Onanong; Munyoo, Bamroong; Tuchinda, Patoomratana; Panbangred, Watanalai

    2016-05-01

    Altholactone exhibited the anti-fungal activity with a high MIC value of 128 μg ml(-1) against Cryptococcus neoformans and Saccharomyces cerevisiae. Fifteen ester derivatives of altholactone 1-15 were modified by esterification and their structures were confirmed by spectroscopic methods. Most of the ester derivatives exhibited stronger anti-fungal activities than that of the precursor altholactone. 3-Bromo- and 2,4-dichlorobenzoates (7 and 15) exhibited the lowest minimal inhibitory concentration (MIC) values against C. neoformans at 16 μg ml(-1), while the 4-bromo-, 4-iodo-, and 1-bromo-3-chlorobenzoates (11-13) displayed potent activity against S. cerevisiae with MIC values of 1 μg ml(-1). In conclusion, this analysis indicates that the anti-fungal activity of altholactone is enhanced by addition of halogenated benzoyl group to the 3-OH group. PMID:26765144

  9. Design, synthesis and evaluation of benzotriazole derivatives as novel antifungal agents.

    PubMed

    Shah, Jay J; Khedkar, Vijay; Coutinho, Evans C; Mohanraj, Krishnapriya

    2015-09-01

    Considering the need for discovery of new antifungal drugs with greater potency and broader spectrum of activity, a new series of 5-substituted benzotriazole derivatives were designed, through structure based design, as inhibitors of fungal cytochrome P450 lanosterol 14-α demethylase. These were further optimized by a combination of iterative medicinal chemistry principles and molecular docking. Based on the best docking scores, some benzotriazole derivatives were synthesized and characterized by IR, (1)H NMR and MS/MS. The molecules were evaluated for their antifungal action against Candida albicans by cup plate method and ergosterol quantification method by UV spectroscopy. Reasonably good correlation between docking scores and antifungal activity were observed. The computational predictions were in consensus with the experimental results. PMID:26117563

  10. Synthesis, Antifungal Activity, and Structure Activity Relationships of Coruscanone A Analogs

    PubMed Central

    Babu, K. Suresh; Li, Xing-Cong; Jacob, Melissa R.; Zhang, Qifeng; Khan, Shabana I.; Ferreira, Daneel; Clark, Alice M.

    2008-01-01

    Coruscanone A, a plant derived cyclopentenedione derivative, showed potent in vitro antifungal activity against Candida albicans and Cryptococcus neoformans, comparable to amphotericin B and fluconazole. A series of analogs have been synthesized by modification of the cyclopentenedione ring, the enolic methoxy functionality, and the side chain styryl moiety of this natural product lead. A structurally close 1,4-benzoquinone analog was also prepared. All the compounds were examined for their in vitro activity against major opportunistic fungal pathogens including C. albicans, C. neoformans and Aspergillus fumigatus, and fluconazole-resistant C. albicans strains, with several analogs demonstrating potent antifungal activity. Structure activity relationship studies indicate that the 2-methoxymethylene-cyclopent-4-ene-1,3-dione structural moiety is the pharmacophore responsible for the antifungal activity of this class of compounds, while the side chain styryl-like moiety plays an important complementary role, presumably contributing to target binding. PMID:17181171

  11. Synthesis, In Vitro Biological Evaluation, and Molecular Docking of New Triazoles as Potent Antifungal Agents.

    PubMed

    Li, Xiang; Liu, Chao; Tang, Sheng; Wu, Qiuye; Hu, Honggang; Zhao, Qingjie; Zou, Yan

    2016-01-01

    Based on the structure of the active site of CYP51 and the structure-activity relationships of azole antifungal compounds that we designed in a previous study, a series of 1-{1-[2-(substitutedbenzyloxy)ethyl]-1H-1,2,3-triazol-4-yl}-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ols (6a-n) were designed and synthesized utilizing copper-catalyzed azide-alkyne cycloaddition. Preliminary antifungal tests against eight human pathogenic fungi in vitro showed that all the title compounds exhibited excellent antifungal activities with a broad spectrum in vitro. Molecular docking results indicated that the interaction between the title compounds and CYP51 comprised π-π interactions, hydrophobic interactions, and the narrow hydrophobic cleft. PMID:26641629

  12. Antifungal activity of chemically different essential oils from wild Tunisian Thymus spp.

    PubMed

    Maissa, Ben Jabeur; Walid, Hamada

    2015-01-01

    Essential oils isolated by using hydrodistillation from the aerial parts of Thymus algeriensis and Thymus capitatus Hoff. et Link. from different locations of Tunisia (Kef, Takelsa, Zaghouan, Fahs and Toukeber) were characterised. The chemical composition was analysed by using gas chromatography/mass spectrometry, the major component of T. capitatus from Kef and T. algeriensis was thymol while carvacrol was the main component of T. capitatus from Zaghouan, Fahs and Toukeber. The antifungal activity of the oils and some pure components was assessed by the in vitro assay against several fungi and oomycetes. T. capitatus (chemotype carvacrol) exhibited the strongest antifungal activity followed by T. capitatus (chemotype thymol) and T. algeriensis, indicating that carvacrol might have a stronger antifungal activity than thymol. PMID:25484099

  13. Comparison of antifungal and antioxidant activities of Acacia mangium and A. auriculiformis heartwood extracts.

    PubMed

    Mihara, Rie; Barry, Karen M; Mohammed, Caroline L; Mitsunaga, Tohru

    2005-04-01

    The effect of heartwood extracts from Acacia mangium (heartrot-susceptible) and A. auriculiformis (heartrot-resistant) was examined on the growth of wood rotting fungi with in vitro assays. A. auriculiformis heartwood extracts had higher antifungal activity than A. mangium. The compounds 3,4',7,8-tetrahydroxyflavanone and teracacidin (the most abundant flavonoids in both species) showed antifungal activity. A. auriculiformis contained higher levels of these flavonoids (3.5- and 43-fold higher, respectively) than A. mangium. This suggests that higher levels of these compounds may contribute to heartrot resistance. Furthermore, both flavonoids had strong 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and laccase inhibition. This suggests that the antifungal mechanism of these compounds may involve inhibition of fungal growth by quenching of free radicals produced by the extracellular fungal enzyme laccase. PMID:16124251

  14. Evaluation of topical antifungal products in an in vitro onychomycosis model.

    PubMed

    Sleven, Reindert; Lanckacker, Ellen; Delputte, Peter; Maes, Louis; Cos, Paul

    2016-05-01

    Many topical commercial products are currently available for the treatment of onychomycosis. However, limited data are available concerning their antifungal activity. Using an in vitro onychomycosis model, the daily application of seven nail formulations was compared to the antifungal reference drug amorolfine (Loceryl(®) ) and evaluated for inhibitory activity against Trichophyton mentagrophytes using an agar diffusion test. Of all commercial nail formulations, only Excilor(®) and Nailner(®) demonstrated inhibitory activity, which was much lower compared to the daily application of Loceryl(®) . However, Excilor(®) showed similar efficacy compared to the conventional weekly application of Loceryl(®) . These results suggest a role for organic acids in the antifungal effect of Excilor(®) (acetic acid, ethyl lactate) and Nailner(®) (lactic acid, citric acid, ethyl lactate) as all tested formulations without organic acids were inactive. PMID:26857689

  15. The Role of Antifungals against Candida Biofilm in Catheter-Related Candidemia

    PubMed Central

    Bouza, Emilio; Guinea, Jesús; Guembe, María

    2014-01-01

    Catheter-related bloodstream infection (C-RBSI) is one of the most frequent nosocomial infections. It is associated with high rates of morbidity and mortality. Candida spp. is the third most common cause of C-RBSI after coagulase-negative staphylococci and Staphylococcus aureus and is responsible for approximately 8% of episodes. The main cause of catheter-related candidemia is the ability of some Candida strains—mainly C. albicans and C. parapsilosis—to produce biofilms. Many in vitro and in vivo models have been designed to assess the activity of antifungal drugs against Candida biofilms. Echinocandins have proven to be the most active antifungal drugs. Potential options in situations where the catheter cannot be removed include the combination of systemic and lock antifungal therapy. However, well-designed and -executed clinical trials must be performed before firm recommendations can be issued. PMID:27025612

  16. Antifungal activities of major tea leaf volatile constituents toward Colletorichum camelliae Massea.

    PubMed

    Zhang, Zheng-Zhu; Li, Ying-Bo; Qi, Li; Wan, Xiao-Chun

    2006-05-31

    A crude glycosidic fraction was prepared from fresh tea leaves and treated with the crude tea enzyme, fractions of cis-3-hexenol, linalool oxide I (cis-furanoid), linalool oxide II (trans-furanoid), linalool, methyl salicylate, geraniol, benzyl alcohol, and 2-phenylethanol were monitored to be the major aglycone moieties by analyzing the released volatiles. The amount of the released aglycone moieties is 5.8 times higher than those in free form. For investigation of the functions of the glycosidically bound form aroma constituents in tea leaves, their antifungal activities were determined by antifungal assay. Geraniol, linalool, methyl salicylate, benzyl alcohol, and 2-phenylethanol exhibited significant antifungal activities toward Colletorichum camelliae Massea, although cis-3-hexenol and linalool oxides showed weaker activities by comparison. Among them, geraniol was shown to be the most potential antifungal substance with a MIC value of 440 microg/mL. The crude glycosidic fraction prepared from tea leaves also exhibited significant antifungal activities in a wide range of concentrations from 2 to 25 mg/mL in a PDA medium. It was deduced that the glycosidically bound volatiles are formed and stored in the intact tissue of tea leaf and hydrolyzed by the actions of both the endogenous and the exogenous glycosidases to release volatiles as antifungal substances when exposed to Colletorichum camelliae Massea. The results suggested that the higher content of the bound form geraniol in tea leaves of var. sinensis might be responsible for their stronger antipathogen properties toward tea leaf blight, as opposed to those of var. assamica. PMID:16719518

  17. Transcriptional regulation of drug-resistance genes in Candida albicans biofilms in response to antifungals.

    PubMed

    Watamoto, T; Samaranayake, L P; Egusa, H; Yatani, H; Seneviratne, C J

    2011-09-01

    Biofilm formation is a major virulence attribute of Candida albicans and is directly associated with therapeutic failure. One method by which Candida acquires antifungal resistance is the expression of drug-resistance genes. This study aimed to evaluate the transcriptional regulation of several genes associated with antifungal resistance of C. albicans under planktonic, recently adhered and biofilm growth modes and in C. albicans biofilms in response to antifungal agents. Initially, the antifungal susceptibility of C. albicans cultures in different growth modes was evaluated by standard antifungal susceptibility testing. Next, to assess CDR1, CDR2, MDR1, ERG11, FKS1 and PIL1 expression, RNA was harvested from cells in each growth mode, and from biofilms after drug treatment, and subjected to quantitative real-time RT-PCR (qRT-PCR). Biofilm C. albicans was more resistant to antifungals than recently adhered cells and stationary-phase planktonic cultures. Transcriptional expression of CDR1, CDR2, MDR1, ERG11 and FKS1 was lower in recently adhered C. albicans than in the stationary-phase planktonic cultures. In contrast, PIL1 levels were significantly increased in recently adhered and biofilm modes of growth. The expression of MDR1 in biofilms greatly increased on challenge with amphotericin B but not with the other drugs tested (P<0.01). ERG11 was significantly upregulated by ketoconazole (P<0.01). Caspofungin and amphotericin B significantly upregulated FKS1 expression, whereas they significantly downregulated PIL1 expression (P<0.01). These results indicate that the expression of drug-resistance genes is associated with higher drug resistance of Candida biofilms, and lay a foundation for future large-scale genome-wide expression analysis. PMID:21474609

  18. Impact of First-Line Antifungal Agents on the Outcomes and Costs of Candidemia

    PubMed Central

    Ha, Young Eun; Joo, Eun-Jeong; Kim, Shin Woo; Jung, Sook-In; Chang, Hyun Ha; Park, Kyong Hwa; Han, Sang Hoon

    2012-01-01

    Candida species are the leading causes of invasive fungal infection among hospitalized patients and are responsible for major economic burdens. The goals of this study were to estimate the costs directly associated with the treatment of candidemia and factors associated with increased costs, as well as the impact of first-line antifungal agents on the outcomes and costs. A retrospective study was conducted in a sample of 199 patients from four university-affiliated tertiary care hospitals in Korea over 1 year. Only costs attributable to the treatment of candidemia were estimated by reviewing resource utilization during treatment. Risk factors for increased costs, treatment outcome, and hospital length of stay (LOS) were analyzed. Approximately 65% of the patients were treated with fluconazole, and 28% were treated with conventional amphotericin B. The overall treatment success rate was 52.8%, and the 30-day mortality rate was 47.9%. Hematologic malignancy, need for mechanical ventilation, and treatment failure of first-line antifungal agents were independent risk factors for mortality. The mean total cost for the treatment of candidemia was $4,743 per patient. Intensive care unit stay at candidemia onset and antifungal switch to second-line agents were independent risk factors for increased costs. The LOS was also significantly longer in patients who switched antifungal agents to second-line drugs. Antifungal switch to second-line agents for any reasons was the only modifiable risk factor of increased costs and LOS. Choosing an appropriate first-line antifungal agent is crucial for better outcomes and reduced hospital costs of candidemia. PMID:22526315

  19. Screening of antifungal agents using ethanol precipitation and bioautography of medicinal and food plants.

    PubMed

    Schmourlo, Gracilene; Mendonça-Filho, Ricardo R; Alviano, Celuta Sales; Costa, Sônia S

    2005-01-15

    In the search for bioactive compounds, bioautography and ethanol precipitation of macromolecules (proteins, polysaccharides, etc.) of plant aqueous extracts were associated in an antifungal screening. Thus, the supernatants, precipitates (obtained by ethanol precipitation) and aqueous extracts were investigated of medicinal and fruit bearing plants used against skin diseases by the Brazilian population. The agar diffusion and broth dilution methods were used to assess the activity against three fungi: Candida albicans, Trichophyton rubrum and Cryptococcus neoformans. The results, evaluated by the diameter of the inhibition zone of fungal growth, indicate that six plant species, among the 16 investigated, showed significant antifungal activity. The minimal inhibitory concentration (MIC) was determined on plant extracts that showed high efficacy against the tested microorganisms. The most susceptible yeast was Trichophyton rubrum and the best antifungal activity was shown by Xanthosoma sagittifolium supernatant. The bioautography was performed only for the aqueous extracts and supernatants of those plants that showed antifungal activity against Candida albicans and Cryptococcus neoformans, using n-butanol/acetic acid/water (BAW) 8:1:1 to develop silica gel TLC plates. Clear inhibition zones were observed for aqueous extracts of Schinus molle (R(f) 0.89) and Schinus terebinthifolius (R(f) 0.80) against Candida albicans, as for supernatant of Anacardium occidentale (R(f) 0.31) against Cryptococcus neoformans. The separation of macromolecules from metabolites, as in the case of Anacardium occidentale, Solanum sp. and Xanthosoma sagittifolium, enhances antifungal activity. In other cases, the antifungal activity is destroyed, as observed for Momordica charantia, Schinus molle and Schinus terebinthifolius. PMID:15619579

  20. In Vitro Activities of Six Antifungal Drugs Against Candida glabrata Isolates: An Emerging Pathogen

    PubMed Central

    Amirrajab, Nasrin; Badali, Hamid; Didehdar, Mojtaba; Afsarian, Mohammad Hosein; Mohammadi, Rasoul; Lotfi, Nazanin; Shokohi, Tahereh

    2016-01-01

    Background Candida glabrata is a pathogenic yeast with several unique biological features and associated with an increased incidence rate of candidiasis. It exhibits a great degree of variation in its pathogenicity and antifungal susceptibility. Objectives The aim of the present study was to evaluate the in vitro antifungal susceptibilities of the following six antifungal drugs against clinical C. glabrata strains: amphotericin B (AmB), ketoconazole (KTZ), fluconazole (FCZ), itraconazole (ITZ), voriconazole (VCZ), and caspofungin (CASP). Materials and Methods Forty clinical C. glabrata strains were investigated using DNA sequencing. The in vitro antifungal susceptibility was determined as described in clinical laboratory standard institute (CLSI) documents (M27-A3 and M27-S4). Results The sequence analysis of the isolate confirmed as C. glabrata and deposited on NCBI GenBank under the accession number no. KT763084-KT763123. The geometric mean MICs against all the tested strains were as follows, in increasing order: CASP (0.17 g/mL), VCZ (0.67 g/mL), AmB (1.1 g/mL), ITZ (1.82 g/mL), KTZ (1.85 g/mL), and FCZ (6.7 g/mL). The resistance rates of the isolates to CASP, FCZ, ITZ, VZ, KTZ, and AmB were 5%, 10%, 72.5%, 37.5%, 47.5%, and 27.5%, respectively. Conclusions These findings confirm that CASP, compared to the other antifungals, is the potent agent for treating candidiasis caused by C. glabrata. However, the clinical efficacy of these novel antifungals remains to be determined. PMID:27540459

  1. In Vitro and In Vivo antifungal activities of selected Cameroonian dietary spices

    PubMed Central

    2014-01-01

    Background Spices and herbs have been used in food since ancient times to give taste and flavor and also as food preservatives and disease remedies. In Cameroon, the use of spices and other aromatic plants as food flavoring is an integral part of dietary behavior, but relatively little is known about their antifungal potential. The present work was designed to assess the antifungal properties of extracts from spices used in Cameroonian dietary. Methods The in vitro antifungal activities of twenty three extracts from twenty one spices were assessed by the broth micro-dilution method against eight fungi. Also, the in vivo activity of Olax subscorpioidea extract (the most active extract) was evaluated in rat model of disseminated candidiasis due to Candida albicans by estimating the fungal burden in blood and kidney. Results Seven extracts (30%) exhibited moderate to significant antifungal activities, inhibiting the growth of the microorganisms at concentrations ranging from 0.048 to 0.39 mg/mL. Olax subscorpioidea extract exhibited the highest antifungal activity particularly against Candida albicans and Candida tropicalis (MIC of 0.097 mg/mL and 0.048 mg/mL respectively). Sixteen extracts (70%) were weakly active (MICs > 6.25 mg/mL). Oral administration of O. subscorpioidea extract at the dose 2 g/kg of body weight (bw) to artificially infected rats revealed a drop in the number of colony forming units per milliliter (cfu/mL) of Candida albicans cells in the blood below the detection limit (100 cfu/mL) while a modest decrease was observed in the kidney. Conclusion The present work shows that some of the spices studied possess interesting antifungal properties and could be used to treat candidiasis. Among the plant species tested, Olax subscorpioidea displayed the most promising result. PMID:24533718

  2. Enhanced production of antifungal lipopeptides by Bacillus amyloliquefaciens for biocontrol of postharvest disease.

    PubMed

    Pretorius, D; van Rooyen, J; Clarke, K G

    2015-03-25

    Food security to sustain increasing populations is a global concern. A major factor threatening food security is crop spoilage during postharvest storage. Reduction of postharvest spoilage has mainly been addressed by the application of synthetic chemicals. Bacillus lipopeptides, specifically lipopeptide homologues exhibiting antifungal efficacy, offer an alternative environmentally benign protocol for reduction of postharvest phytopathogens. This work is directed towards Bacillus lipopeptide production for biocontrol of postharvest phytopathogens in general and fungal phytopathogens in particular. Bacillus amyloliquefaciens DSM 23117 was identified as an organism with superior potential for lipopeptide production, via screening of 4 Bacillus candidates, in terms of antifungal lipopeptide concentration, yield, productivity and preferred homologue ratio. Efficacy of B. amyloliquefaciens lipopeptides against Botrytis cinerea substantiated appropriateness of this Bacillus species. Subsequent process modification of B. amyloliquefaciens cultures demonstrated that the concentration and ratio of the lipopeptides were significantly influenced by process conditions and further, distinguished nitrate and oxygen availability as key parameters defining optimal lipopeptide production. Discrete B. amyloliquefaciens cultures supplied with 4, 8, 10 and 12 g/L NH4NO3 demonstrated optimal lipopeptide concentration, yield and productivity, with respect to both total and antifungal lipopeptides, in the culture containing 8 g/L NH4NO3. Enhancement of total and antifungal lipopeptide kinetics similar to those quantified on increasing the nitrate from 4 to 8 g/L NH4NO3 were exhibited in B. amyloliquefaciens cultures when the oxygen in the sparge gas was increased from 21 to 30 mol%. The enhancement of lipopeptide production under conditions of increased nitrate and increased oxygen supply is explained in terms of increased availability of nitrogen for synthesis. This work has

  3. Identification, characterization, and regulation of a novel antifungal chitosanase gene (cho) in Anabaena spp.

    PubMed

    Gupta, Vishal; Prasanna, Radha; Natarajan, Chitra; Srivastava, Ashish Kumar; Sharma, Jitender

    2010-05-01

    Two contrasting cyanobacterial species (Anabaena fertilissima and Anabaena sphaerica) were selected based on differences in antifungal behavior in order to study the mechanism for production of an antifungal enzyme and the genes responsible for this production. In A. fertilissima, chitosanase and antifungal activities were increased significantly under of growth-limiting conditions (8 of light and 16 h of darkness). The lack of such activities in A. sphaerica was associated with high levels of protein that accumulated during the stationary phase (at 28 days) under the same light conditions. The gene putatively responsible for chitosanase and antifungal activities was amplified using specific primers, and sequence analysis of the amplified products (1.086 and 1.101 kb in A. sphaerica and A. fertilissima, respectively) showed that they belong to the glycoside hydrolase 3 (GH3)-like family of Anabaena variabilis ATCC 29413. Pairwise alignment of the corresponding protein sequences identified a putative signal peptide (amino acids 1 to 23) and some amino acid changes in the sequence of A. fertilissima which may be responsible for functioning of the chitosanase and the observed antifungal activity. Hydrolysis of the chitosan oligosaccharide (GlcN)(5) to (GlcN)(2) and (GlcN)(3) confirmed the presence of chitosanase activity in A. fertilissima. Site-directed mutagenesis of the A. fertilissima chitosanase-encoding gene (cho) led to identification of catalytic residues (Glu-121 and Glu-141) important for the antifungal effect of the cho product. The level of expression of cho was monitored by quantitative real-time reverse transcription-PCR, which indicated that transcription of this gene is significantly enhanced under conditions that retard growth, such as a long dark period. PMID:20228117

  4. Isolation, Purification, and Structural Identification of an Antifungal Compound from a Trichoderma Strain.

    PubMed

    Li, Chong-Wei; Song, Rui-Qing; Yang, Li-Bin; Deng, Xun

    2015-08-01

    Trichoderma strain T-33 has been demonstrated to have inhibitory effect on the fungus species Cytospora chrysosperma. Here, an active antifungal compound was obtained from Trichoderma strain T-33 extract via combined separation technologies, including organic solvent extraction, liquid chromatography, and thin-layer chromatography. The purified compound was further characterized by advanced analytical technologies to elucidate its chemical structure. Results indicated that the active antifungal compound in Trichoderma strain T-33 extract is 2,5- cyclohexadiene-1,4-dione-2,6-bis (1,1-dimethylethyl). PMID:25876599

  5. Production and biological activities of a new antifungal antibiotic, TAN-950 A.

    PubMed

    Hakoda, S; Tsubotani, S; Iwasa, T; Suzuki, M; Kondo, M; Harada, S

    1992-06-01

    A novel antifungal antibiotic, TAN-950 complex, was isolated from the culture filtrate of Streptomyces platensis A-136 (IFO 14603, FERM BP-1786). The water-soluble amphoteric substances in this complex were purified by chromatography using ion-exchange resins, QAE-Sephadex and adsorptive resins and were designated TAN-950 A and TAN-950 A-E mixture. The molecular formula of TAN-950 A was determined to be C6H7N2O4Na for the sodium salt. This new amino acid antibiotic showed antifungal activity against Candida albicans in vitro and in vivo, and had low toxicity in mice. PMID:1500350

  6. Antifungal activity of chalcones: a mechanistic study using various yeast strains.

    PubMed

    Lahtchev, K L; Batovska, D I; Parushev, St P; Ubiyvovk, V M; Sibirny, A A

    2008-10-01

    We reported the synthesis, antifungal evaluation and study on substituent effects of 21 chalcones. A lot of genetically defined strains belonging to different yeast genera and species, namely Saccharomyces cerevisiae, Hansenula polymorpha and Kluyveromyces lactis, were used as test organisms. Concerning the mode of the antifungal action of chalcones it was shown that DNA was probably not the main target for the chalcones. It was revealed that the yeast's intracellular glutathione and cysteine molecules play significant role as defence barrier against the chalcone action. It was also shown that chalcones may react with some proteins involved in cell separation. PMID:18280009

  7. The contribution of Aspergillus fumigatus stress responses to virulence and antifungal resistance.

    PubMed

    Brown, Neil A; Goldman, Gustavo H

    2016-03-01

    Invasive aspergillosis has emerged as one of the most common life-threatening fungal disease of humans. The emergence of antifungal resistant pathogens represents a current and increasing threat to society. In turn, new strategies to combat fungal infection are urgently required. Fungal adaptations to stresses experienced within the human host are a prerequisite for the survival and virulence strategies of the pathogen. Here, we review the latest information on the signalling pathways in Aspergillus fumigatus that contribute to stress adaptations and virulence, while highlighting their potential as targets for the development of novel combinational antifungal therapies. PMID:26920884

  8. Antifungal bis[bibenzyls] from the Chinese liverwort Marchantia polymorpha L.

    PubMed

    Niu, Chong; Qu, Jian-Bo; Lou, Hong-Xiang

    2006-01-01

    Bioassay-guided separation of the antifungal constituents of the Chinese liverwort Marchantia polymorpha L. (Marchantiaceae) led to the isolation of seven bis[bibenzyl]-type macrocycles. On the basis of NMR and MS analyses, the three new compounds plagiochin E (1), 13,13'-O-isoproylidenericcardin D (4), and riccardin H (7) were identified, together with four known compounds: marchantin E (2), neomarchantin A (3), marchantin A (5), and marchantin B (6). Their antifungal activities against Candida albicans were determined by TLC bioautography. PMID:17193213

  9. The chemical composition of some Lauraceae essential oils and their antifungal activities.

    PubMed

    Simić, A; Soković, M D; Ristić, M; Grujić-Jovanović, S; Vukojević, J; Marin, P D

    2004-09-01

    The antifungal activity of Aniba rosaeodora, Laurus nobilis, Sassafras albidum and Cinnamomum zeylanicum essential oils were investigated against 17 micromycetes. Among the tested fungal species were food poisoning, spoilage fungi, plant and animal pathogens. In order to determine fungistatic and fungicidal concentrations (MIC and MFC) macrodilution and microdilution tests were used. Linalool was the main component in the essential oil of A. rosaeodora, while 1.8-cineole was dominant in L. nobilis. In sassafras essential oil safrole was the major component and in the oil of C. zeylanicum the main component was trans-cinnamaldehyde. The essential oil of cinnamon showed the strongest antifungal activity. PMID:15478207

  10. Design, synthesis, and antifungal activities of novel triazole derivatives containing the benzyl group

    PubMed Central

    Xu, Kehan; Huang, Lei; Xu, Zheng; Wang, Yanwei; Bai, Guojing; Wu, Qiuye; Wang, Xiaoyan; Yu, Shichong; Jiang, Yuanying

    2015-01-01

    In previous studies undertaken by our group, a series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols (1a–r), which were analogs of fluconazole, was designed and synthesized by click chemistry. In the study reported here, the in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi. Compounds 1a, 1q, and 1r showed the more antifungal activity than the others. PMID:25792806

  11. Experimental and theoretical approach of nanocrystalline TiO2 with antifungal activity

    NASA Astrophysics Data System (ADS)

    Longo, Valeria M.; Picon, Francini C.; Zamperini, Camila; Albuquerque, Anderson R.; Sambrano, Julio R.; Vergani, Carlos E.; Machado, Ana L.; Andrés, Juan; Hernandes, Antônio C.; Varela, José A.; Longo, Elson

    2013-07-01

    Using a solvothermal method for this research we synthesized nanocrystalline titanium dioxide (nc-TiO2) anatase particles with a mean diameter of 5.4 nm and evaluated their potential antifungal effect against planktonic cells of Candida albicans without UV radiation. To complement experimental data, we analyzed structural and electronic properties of both the bulk and the (1 0 1) surface of anatase by first-principles calculations. Based on experimental and theoretical results, a reactive O2H and OH species formation mechanism was proposed to explain the key factor which facilitates the antifungal activity.

  12. Bioactivity guided isolation of antifungal compounds from the liverwort Bazzania trilobata (L.) S.F. Gray.

    PubMed

    Scher, Jochen M; Speakman, John-Bryan; Zapp, Josef; Becker, Hans

    2004-09-01

    A dichloromethane and a methanol extract of the liverwort Bazzania trilobata showed antifungal activity against the phytopathogenic fungi Botrytis cinerea, Cladosporium cucumerinum, Phythophthora infestans, Pyricularia oryzae and Septoria tritici. Bioautography on thin-layer chromatograms was used to isolate six antifungal sesquiterpenes: 5- and 7-hydroxycalamenene, drimenol, drimenal, viridiflorol, gymnomitrol and three bisbibenzyls: 6 ',8'-dichloroisoplagiochin C, isoplagiochin D and 6'-chloroisoplagiochin D. Furthermore we report the isolation of gymnomitr-8(12)-en-4-one and the new coumarin 7,8-dihydroxycoumarin-7-O-beta-D-glucuronide. Their structures have been elucidated based on extensive NMR spectral evidence. PMID:15451321

  13. Salvage therapy with topical antifungal for Aspergillus fumigatus empyema complicating extrapleural pneumonectomy

    PubMed Central

    Purohit, Manoj; Guleri, Achyut; Zacharias, Joseph

    2012-01-01

    We describe an unusual case of Aspergillus fumigatus empyema and bronchopleural fistulae after extrapleural pneumonectomy (EPP) and chemoradiotherapy (CRT), which was treated successfully under salvage conditions with debridement, an innovative topical antifungal application and supplemented systemic antifungal therapy and which went on for a definitive surgical procedure. Combinations of CRT and EPP have been recommended in a select group of patients with malignant mesothelioma. Irrespective of the combination, EPP is associated with mortality in the range of 4–15% and a complication rate as high as 62%. PMID:22617507

  14. The synthesis and synergistic antifungal effects of chalcones against drug resistant Candida albicans.

    PubMed

    Wang, Yuan-Hua; Dong, Huai-Huai; Zhao, Fei; Wang, Jie; Yan, Fang; Jiang, Yuan-Ying; Jin, Yong-Sheng

    2016-07-01

    To identify effective and low toxicity synergistic antifungal compounds, 24 derivatives of chalcone were synthesized to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant Candida albicans. This was done via methods established by the clinical and laboratory standards institute (CLSI). Of the synthesized compounds, 2'-hydroxy-4'-methoxychalcone (8) exhibited the most potent in vitro (FICI=0.007) effects. The structure activity relationship of the compounds are then discussed. PMID:27210436

  15. Design, synthesis, and antifungal activities of novel triazole derivatives containing the benzyl group.

    PubMed

    Xu, Kehan; Huang, Lei; Xu, Zheng; Wang, Yanwei; Bai, Guojing; Wu, Qiuye; Wang, Xiaoyan; Yu, Shichong; Jiang, Yuanying

    2015-01-01

    In previous studies undertaken by our group, a series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols (1a-r), which were analogs of fluconazole, was designed and synthesized by click chemistry. In the study reported here, the in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi. Compounds 1a, 1q, and 1r showed the more antifungal activity than the others. PMID:25792806

  16. Thiourea derivatives incorporating a hippuric acid moiety: synthesis and evaluation of antibacterial and antifungal activities.

    PubMed

    Abbas, Samir Y; El-Sharief, Marwa A M Sh; Basyouni, Wahid M; Fakhr, Issa M I; El-Gammal, Eman W

    2013-06-01

    New series of thiourea derivatives incorporating a hippuric acid moiety have been synthesized through the reaction of 4-hippuric acid isothiocyanate with various nitrogen nucleophiles such as aliphatic amines, aromatic amines, sulfa drugs, aminopyrazoles, phenylhydrazine and hydrazides. The synthesized compounds were tested against bacterial and fungal strains. Most of compounds, such as 2-(4-(3-(3-bromophenyl)thioureido)benzamido)acetic acid and 2-(4-(3-(4-(N-pyrimidin-2-ylsulfamoyl)phenyl)thioureido)benzamido)acetic acid, showed significant antibacterial and antifungal activities. These compounds comprise a new class of promising broad-spectrum antibacterial and antifungal agents. PMID:23644194

  17. Novel micelle formulations to increase cutaneous bioavailability of azole antifungals.

    PubMed

    Bachhav, Y G; Mondon, K; Kalia, Y N; Gurny, R; Möller, M

    2011-07-30

    Efficient topical drug administration for the treatment of superficial fungal infections would deliver the therapeutic agent to the target compartment and reduce the risk of systemic side effects. However, the physicochemical properties of the commonly used azole antifungals make their formulation a considerable challenge. The objective of the present investigation was to develop aqueous micelle solutions of clotrimazole (CLZ), econazole nitrate (ECZ) and fluconazole (FLZ) using novel amphiphilic methoxy-poly(ethylene glycol)-hexyl substituted polylactide (MPEG-hexPLA) block copolymers. The CLZ, ECZ and FLZ formulations were characterized with respect to drug loading and micelle size. The optimal drug formulation was selected for skin transport studies that were performed using full thickness porcine and human skin. Penetration pathways and micellar distribution in the skin were visualized using fluorescein loaded micelles and confocal laser scanning microscopy. The hydrodynamic diameters of the azole loaded micelles were between 70 and 165nm and the corresponding number weighted diameters (d(n)) were 30 to 40nm. Somewhat surprisingly, the lowest loading efficiency (<20%) was observed for CLZ (the most hydrophobic of the three azoles tested); in contrast, under the same conditions, ECZ was incorporated with an efficiency of 98.3% in MPEG-dihexPLA micelles. Based on the characterization data and preliminary transport experiments, ECZ loaded MPEG-dihexPLA micelles (concentration 1.3mg/mL; d(n)<40nm) were selected for further study. ECZ delivery was compared to that from Pevaryl® cream (1% w/w ECZ), a marketed liposomal formulation for topical application. ECZ deposition in porcine skin following 6h application using the MPEG-dihexPLA micelles was >13-fold higher than that from Pevaryl® cream (22.8±3.8 and 1.7±0.6μg/cm(2), respectively). A significant enhancement was also observed with human skin; the amounts of ECZ deposited were 11.3±1.6 and 1.5±0.4μg/cm(2

  18. [In vitro antifungal susceptibility, in vivo antifungal activity and security from a natural product obtained from sunrise oil (AMO3) against dermatophytes].

    PubMed

    Thomson M, Pamela; Anticevic C, Sonia; Rodríguez B, Héctor; Silva V, Víctor

    2011-12-01

    This work studied safety and antifungal activity of ozonized sunflower oil (AMO3) against dermatophytes. AMO3 was prepared through a new original process that modifies the oil before ozonation by alcoholic catalytic esterification. Susceptibility was studied in 41 dermatophytes by agar diffusion and broth microdilution tests. The experimental model to assess the topical safety of the oil included 60 CF1 mice divided in three groups that were treated with vaseline (control), 1% AMO3 and 50% AMO3 (overdose), respectively. Then, experimental dermatophytosis was induced in CF1 mice. Seventy-five individuals were selected and divided in 5 groups that were treated once a day with placebo, cream with 1%, 2% and 3% AMO3 plus an untreated control group. This new natural product showed antifungal activity against all strains studied. The MIC ranged between was 0,125 and 1%, while minimum fungicidal concentration (MFC) was 2%. The application of vaseline and AMO3 1% and 50% did not produce clinical or histopathological lesions. The mice with dermatophytosis that were treated with 1%, 2% and 3% AMO3 showed 100% clinical cure and 94% average mycological cure, exceeding placebo and control groups (p < 0,05). This product exhibits high antifungal activity and could be a safe alternative for ringworm topical treatment. PMID:22286673

  19. Antifungal effect of various essential oils against Candida albicans. Potentiation of antifungal action of amphotericin B by essential oil from Thymus vulgaris.

    PubMed

    Giordani, R; Regli, P; Kaloustian, J; Mikaïl, C; Abou, L; Portugal, H

    2004-12-01

    The antifungal effect of the essential oil from Satureja montana L., Lavandula angustifolia Mill., Lavandula hybrida Reverchon, Syzygium aromaticum (L.) Merril and Perry, Origanum vulgare L., Rosmarinus officinalis L. and six chemotypes of Thymus vulgaris L. on Candida albicans growth were studied. The most efficiency was obtained with the essential oil from Thymus vulgaris thymol chemotype (MIC 80% = 0.016 microL/mL and Kaff = 296 microL/mL). The presence in the culture medium of essential oil from Thymus vulgaris thymol chemotype (0.01, 0.1, 0.2, 0.3 microg/mL) and amphotericin B involved a decrease of the MIC 80% of amphotericin B. In contrast, the combination of amphotericin B and low concentrations (0.00031-0.0025 microg/mL) of essential oil was antagonistic. The strongest decrease (48%) of the MIC 80% was obtained with medium containing 0.2 microL/mL of essential oil. These results signify that the essential oil of Thymus vulgaris thymol chemotype potentiates the antifungal action of amphotericin B suggesting a possible utilization of this essential oil in addition to antifungal drugs for the treatment of mycoses. PMID:15742351

  20. Antifungal quinazolinones from marine-derived Bacillus cereus and their preparation.

    PubMed

    Xu, Zhihong; Zhang, Yapeng; Fu, Haichao; Zhong, Huimin; Hong, Kui; Zhu, Weiming

    2011-07-01

    Two new quinazolinones alkaloids, R(+)-2-(heptan-3-yl)quinazolin-4(3H)-one (1) and (2R,3'R)+(2S,3'R)-2-(heptan-3-yl)-2,3-dihydroquinazolin-4(1H)-one (2) (a pair of epimers), as well as seven known analogues, 2-methylquinazolin-4(3H)-one (3), 2-benzylquinazolin-4(3H)-one (4), cyclo-(Pro-Ile), cyclo-(Pro-Leu), cyclo-(Pro-Val), cyclo-(Pro-Phe), and cyclo-(Tyr-Pro) were isolated from the n-butyl alcohol extract of the marine-derived bacterium Bacillus cereus 041381. The new compounds were identified by spectroscopic analysis and chemical synthesis. Four optical isomers 5-8 were also synthesized. Compounds 1-8 all showed moderate antifungal activity against Candida albicans with MIC values of 1.3-15.6 μM. Compound 5 exhibits the most powerful antifungal activity, which may reveal that S-configuration and 2,3-double bond were necessary for antifungal activity, and the racemization at C-2 and C-3' reduced the antifungal activity. PMID:21612927