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At least 433 records · Page 24Linked to original sources
PubMed2005

FTR1335 is a novel synthetic inhibitor of Candida albicans N-myristoyltransferase with fungicidal activity.

Inhibitors of the fungal enzyme N-myristoyltransferase (Nmt) reduce fungal growth, as this enzyme is essential for viability. We found that a newly synthesized benzothiazole derivative, (1R,3S)-N-{2-[(cyclopeanthylcarbonyl) amino]-benzothiazol-6-yl}-3-[(2-naphthylmethyl) amino] cyclohexanecarboxamide (FTR1335), preferentially inhibited Candida albicans Nmt (CaNmt) in a dose-dependent manner. The 50% inhibitory concentration (IC(50)) for CaNmt was 0.49 nM, which was much lower than the 5400 nM IC(50) for human Nmt (HsNmt1). The mode of CaNmt inhibition was competitive with the substrate peptide and non-competitive with myristoyl-CoA. Moreover, FTR1335 showed strong antifungal activity in vitro, and the minimum fungicidal concentration for C. albicans was 0.78 microM. These results indicate that FTR1335 might represent a novel family of Nmt inhibitors with fungicidal activity.

Acyltransferases↗
PubMed2002

[Fungicidal activity of liranaftate against Trichophyton rubrum].

The fungicidal activities of thiocarbamate antifungal agent liranaftate were studied by determining the MIC and the MCC against Trichophyton rubrum with the Milliflex -100 Test System and by determining the time-kill curve in comparison to that of six reference agents. Liranaftate and lanoconazole both showed excellent fungistatic activity against the conidia of T. rubrum. For each of these agents, the MIC after 14 days of contact was 0.009 g/ml. The liranaftate-induced decrease in the MCC occurred from 9 days onwards; MCC at 14 days was 0.039 g/ml. The MCC for tolciclate was also reduced from 9 days onwards, but that of amorolfine, lanoconazole, neticonazole, clotrimazole and bifonazole was not lowered up to 14 days. Similar results were obtained when the studies were performed with germinated conidia. The time-kill curves showed that both liranaftate and tolciclate, at concentrations ranging from 2 to 32 times the MICs, achieved a decrease in viable counts to below the detection limit within 7 to 9 days. In experiments with low levels of inoculum, only amorolfine produced a decrease to below the detection level, and that occurred at 14 days; no reduction in viable counts was observed up to 14 days with the four azole agents. Our data suggest that antifungal agents of the thiocarbamate class possess the most potent fungicidal activity against dermatophytes; these are followed in order by morpholine and azole antifungals.

Antifungal Agents↗
PubMed2003

Fungicidal effects of chemical disinfectants, UV light, desiccation and heat on the amphibian chytrid Batrachochytrium dendrobatidis.

The efficacy of a number of disinfection treatments was tested on in vitro cultures of the fungus Batrachochytrium dendrobatidis, the causative agent of chytridiomycosis in amphibians. The aim was to evaluate the fungicidal effects of chemical disinfectants, sterilising ultraviolet (UV) light, heat and desiccation, using methods that were feasible for either disinfection in the field, in amphibian husbandry or in the laboratory. The chemical disinfectants tested were: sodium chloride, household bleach (active ingredient: sodium hypochlorite), potassium permanganate, formaldehyde solution, Path-X agricultural disinfectant (active ingredient: didecyl dimethyl ammonium chloride, DDAC), quaternary ammonium compound 128 (DDAC), Dithane, Virkon, ethanol and benzalkonium chloride. In 2 series of experiments using separate isolates of B. dendrobatidis, the fungicidal effect was evaluated for various time periods and at a range of chemical concentrations. The end point measured was death of 100% of zoospores and zoosporangia. Nearly all chemical disinfectants resulted in 100%, mortality for at least one of the concentrations tested. However, concentration and time of exposure was critical for most chemicals. Exposure to 70% ethanol, 1 mg Virkon ml(-1) or 1 mg benzalkonium chloride ml(-1) resulted in death of all zoosporangia after 20 s. The most effective products for field use were Path-X and the quaternary ammonium compound 128, which can be used at dilutions containing low levels (e.g. 0.012 or 0.008%, respectively) of the active compound didecyl dimethyl ammonium chloride. Bleach, containing the active ingredient sodium hypochlorite, was effective at concentrations of 1% sodium hypochlorite and above. Cultures did not survive complete drying, which occurred after <3 h at room temperature. B. dendrobatidis was sensitive to heating, and within 4 h at 37 degrees C, 30 min at 47 degrees C and 5 min at 60 degrees C, 100% mortality occurred. UV light (at 1000 mW m(-2) with a wavelength of 254 nm) was ineffective at killing B. dendrobatidis in culture.

Cells, Cultured↗
PubMed2006

Combined use of the biocontrol bacterium Pseudomonas fluorescens strain LRB3W1 with reduced fungicide application for the control of tomato Fusarium wilt.

Pseudomonas fluorescens strain LRB3W1 inhibited the mycelial growth of Fusarium oxysporum f. sp. lycopersici and suppressed the Fusarium wilt of tomato. The chemical fungicide, benomyl, did not suppress the disease incidence at low concentrations. However, the disease incidence was decreased by the combined application of benomyl at low concentrations with strain LRB3W1. Combined application of benomyl with the bacterium was more effective than treatment with the bacterium alone. The survival of strain LRB3W1 was not influenced by the presence of benomyl. This combined use of the biocontrol bacterium, strain LRB3W1, and a fungicide, benomyl, should be an attractive approach for suppressing tomato wilt.

Antifungal Agents↗
PubMed1990

Ethylenethiourea in air and in urine as an indicator of exposure to ethylenebisdithiocarbamate fungicides.

Ethylenethiourea (ETU) is a ubiquitous impurity of the ethylenebisdithiocarbamate (EBDC) fungicides widely used in agriculture and forestry. In the present study, ETU was used as a measure of the exposure to EBDC on potato farms and in pine nurseries during the application of EBDC fungicides and the weeding of the sprayed vegetation. Biological and hygienic monitoring was carried out through the analysis of ETU in the breathing zone and the urine of exposed workers. Even if the concentrations of ETU in the ambient air of pine nurseries exceeded those of potato farms, the concentrations of ETU in the urine of potato farmers exceeded those of pine nursery workers. This result may have been due better protective equipment in the pine nurseries. The excretion rate was 6-10 ng/h during the first 60 h after the cessation of exposure, and it diminished thereafter to 0.2 ng/h over a 22-d observation period.

Adult↗
PubMed1976

Misuse of organomercury fungicides in Brazil.

A methoxyethyl mercuric compound, licensed in Brazil as a fungicide for seed dressing, was widely used for spraying tomato and other vegetable crops in 1966 and 1967.Mercury residues ranging from 0.05 to 0.30 mg/kg were detected in 14% of the tomatoes, 13% of other vegetable samples, and 57% of the tomato paste batches.A wide campaign through newspapers, radio, and television was quickly established to educate farmers and the population in general on the hazards of ingestion of mercury-contaminated food.All samples of tomatoes and other vegetables positive for mercury (residues above 0.05 mg/kg) were destroyed. Inspection posts on the main roads and highways prevented the delivery of contaminated food to cities and food processing plants.The sale of organomercury fungicides is now controlled in Brazil; however, treated seeds which are not planted may be diverted to human or animal consumption. There is no official record of accidents, but occasional cases of poisoning are known.The mercury residue level in Brazilian fish is low, indicating that environmental pollution by mercury is not a big problem in the country. However, some fresh-water and estuarine fish may contain mercury residues ranging from 0.01 to 0.66 mg/kg.

Animals↗
PubMedDate not supplied

Effect of fungicides on the production of amylase by Rhizopus oryzae.

Seven fungicides (Brassicol), captan, Dithane M-45, Fytolan, Parasan, Sulfex and Thiram) were tested for their effect on the production of amylase enzyme by Rhizopus oryzae. The activity of amylase was determined by cup-plate method. All the fungicides were found inhibitory for the synthesis of amylase. Out of these, Parasan was the most effective causing hundred percent inhibition at 0.025% concentration. No amylase production was recorded when Thiram, Fytolan, Brassicol, Captan and Dithane M-45 were used at 0.5, 1.5, 2.0, 2.0, and 2.0% concentration respectively. Sulfex was found to be less effective, as hundred percent inhibition of amylase production has not been recorded even at 3.0% concentration.

Amylases↗
PubMed1992

4-oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus I.

Candida albicans and Cryptococcus neoformans are major causes of systemic fungal infections, particularly in patients with acquired immunodeficiency syndrome. Metabolic labeling studies revealed that these organisms synthesize a small number of N-myristoylproteins, the most prominent being 20-kDa ADP-ribosylation factors (Arfs). C. albicans Arf has approximately 80% identity with the essential Arf1 and Arf2 proteins of Saccharomyces cerevisiae. [3H]Myristic acid analogs with oxygen for -CH2- substitutions at C4, C6, C11, and C13 are incorporated into cellular N-myristoylproteins, phospholipids, and neutral lipids produced by these three yeasts during exponential growth at 30 degrees C in complex media. Analog- and organism-specific differences in the efficiency of labeling of proteins and lipid classes were observed. The effects of oxatetradecanoic acids with oxygen for -CH2- substitutions at C3-C13 on C. neoformans, C. albicans, and S. cerevisiae were assessed during mid-log phase growth at 30 degrees C. A single dose of 3-oxa-, 4-oxa-, 5-oxa- or 6-oxatetradecanoic acid (O3-O6, final concentration = 300 microM) was able to inhibit growth of C. neoformans in the order O4 greater than O5 greater than O3 approximately O6. The other compounds were inactive. 4-Oxatetradecanoic acid was fungicidal, producing a 10,000-fold reduction in viable cell number 1 h after administration and continued suppression of cell growth for 7 h. A clear dose response was observed over a concentration range of 100-300 microM. 4-Oxatridecanoic acid was 100-fold less potent in reducing cell viability than 4-oxatetradecanoic acid but more potent than 5-oxatridecanoic acid. O4 produced approximately 10-100-fold reductions in the viability of C. albicans and S. cerevisiae at 300-500 microM, respectively, whereas O5 and O6 were less active. Since N-myristoylation of the Pr55gag polyprotein precursor produced by human immunodeficiency virus I (HIV-I) is essential for its assembly, we also assessed the antiviral effects of 4-oxatetradecanoic acid. O4 is able to produce a 50% reduction in the replication of HIV-I in acutely infected human T-lymphocyte cell lines at a concentration of 18 microM. Together, these data suggest that (i) the position of the oxygen for methylene substitution is a critical determinant of the fungicidal activity of O4 and (ii) NMT may be an attractive therapeutic target for treating opportunistic fungal infections in patients infected with HIV-I.

ADP-Ribosylation Factor 1↗
PubMedDate not supplied

[Effect of radiofrequency of electromagnetic radiation on yeast sensitivity to fungicide antibiotics].

Saccharomyces cerevisiae UCM Y-517, Candida utilis UCM Y-961 and Schizosaccharomyces pombe UCM Y-94T have been studied for their sensitivity to fungicide antibiotics under the effect of electromagnetic radiation (40.68 MHz, 15 and 30 W). Yeast sensitivity to nystatin, amphotericin B, klotrimazol, itrakonazol, flukonazol as well as the effects arising as a result of the effect of radiofrequency radiation are characterized by species specificity. Irradiation did not exert statistically reliable effect on S. cerevisiae and S. pombe sensitivity to fungicide antibiotics. The increase of resistance of C. utilis to antibiotics (growth delay zones were absent in 70-90% of experiments) in the case of preliminary irradiation of this strain was stated. Separate preliminary irradiation of antibiotics did not result in the change of their antifungal activity. The arising effects were noticed to depend on the radiation power. Possible reasons of species specificity in sensing electromagnetic radiation are considered.

Antifungal Agents↗
PubMedDate not supplied

[Mutagenic action of synthetic fungicides and drugs of biological origin on microorganisms].

Gene-toxical effect of biological and synthetical fungicides on auxotrophic test-cultures of Salmonella typhimuriun TA 100 and TA 98, and Escherichia coli WP2 has been studied. Biological drugs on the basis of hytosan (mycosan and mycosan-new) act as weak mutagens. Synthetical fungicides on the basis of benomil and tiram, on the contrary, cause higher frequency of mutation. The exceeding of the recommended doses of these drugs significantly increases gene-toxical loading. This evidences for a necessity to revise agrotechnologies in the direction of decrease of the existing standard.

Escherichia coli↗
PubMed1992

In vitro comparative study of the fungistatic and fungicidal activity of sertaconazole and other antifungals against Candida albicans.

The fungistatic and fungicidal activity of 7-chloro-3-[1-(2, 4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) against Candida albicans was determined and compared with that obtained for other antifungals. The fungistatic activity of sertaconazole, evaluated through the MIC obtained in Sabouraud and YNB media, gave results comparable to those obtained with miconazole and clotrimazole, and superior to those presented by bifonazole and ketoconazole. The fungicidal activity, evaluated by means of the 90% reduction in viable cells, took place at a concentration of 8 micrograms/ml for sertaconazole and at higher concentrations for the other drugs studied.

Antifungal Agents↗
PubMed1992

Direct membrane-damaging effect of sertaconazole on Candida albicans as a mechanism of its fungicidal activity.

The direct action of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy- methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) on the membrane integrity of C. albicans is studied by quantifying the leakage of intracellular adenosine triphosphate (ATP) into the medium as an index of the changes in membrane permeability and integrity and cell viability of the culture used. Sertaconazole caused a dose-dependent decrease in intracellular ATP after only 10-min exposure and a concomitant significant increase in extracellular ATP. This behaviour is characteristic of antifungals which are fungicidal as a result of a direct membrane damage. Thus sertaconazole, in addition to the mechanism of action responsible for its fungistatic activity (inhibition of ergosterol synthesis), has a second mechanism of action providing a significant fungicidal activity due to direct cell membrane damage.

Adenosine Triphosphate↗
PubMed1987

Activation of pulmonary macrophages for fungicidal activity by gamma-interferon or lymphokines.

The ability of murine recombinant gamma interferon (IFN) or lymphokines to enhance the fungicidal activity of murine pulmonary macrophages (PuM) was studied in in vitro. PuM monolayers were incubated overnight with IFN, lymph node cells (LNC) plus concanavalin A, supernatants from Con A stimulated LNC or spleen cell cultures (Con A Sup), or tissue culture medium (TCM) +/- Con A (5 micrograms/ml) or +/- lipopolysaccharide (LPS, 10 ng to 10 micrograms/ml). After treatment, culture fluids were removed and PuM were challenged for 4 h with the yeast-form Blastomyces dermatitidis or 2 h with Candida albicans. Inoculum colony forming units (CFU) of B. dermatitidis were significantly reduced by PuM treated with 1000 U/ml of IFN (25 +/- 3%), Con A Sup (25 +/- 3%) or LNC plus Con A (37-44%), but not by TCM, ConA or LPS. Candida albicans was killed by PuM treated with Con A Sup (33 +/- 8%) or LNC plus Con A (30-43%), but not by TCM, Con A, or LPS, and the activity of Con A Sup was neutralized by anti-IFN antibody. Candida albicans was not significantly killed by PuM treated with IFN doses ranging from 1 to 10(5) U/ml; nor did addition of LPS to IFN, or prolonged (3 day) treatment with IFN, result in significant killing of C. albicans by PuM. However, IFN (100 U/ml) could activate resident peritoneal macrophages for significant candidacidal activity (63%). These data indicate that PuM can be activated for fungicidal activity, and that PuM differ from resident peritoneal macrophages with regard to induction of candidacidal activity by recombinant gamma-IFN.

Animals↗
PubMed1988

Failure of phenobarbitone to potentiate the adverse effects of two ethylene-bis-dithiocarbamate (EBDC) fungicides.

The effects of Mancozeb and Zineb, two dithiocarbamate fungicides used to protect vegetables, on rat thyroid and liver function were studied in an acute and a chronic trial. These compounds may be spontaneously or metabolically transformed to ethylene thiourea, a goitrogenic, mutagenic and teratogenic molecule. Sex linked differences in sensitivity and the possibility that toxicity might be potentiated through induction of the microsomal drug metabolising system by phenobarbitone were investigated. When compared with the findings of Ugazio et al. (1985) on the toxicity of ethylene thiourea, the results obtained in this study, bearing in mind the doses employed and the fact that no potentiation by phenobarbitone was observed, suggest that the risks associated with exposure to these two fungicides are less severe than had been supposed.

Animals↗
PubMedDate not supplied

[Study of the effect of the fungicide zineb on microorganisms].

Changes in yeast cells induced by the fungicide zineb were studied using biochemical, genetic techniques and electron microscopy. The primary changes involved anabolic processes since RNA and protein content increased in the cells. The data were consistent with a larger size of mitochondria. The oxidative-reductive activity of cell extracts did not change under the action of the fungicide. Zineb at a concentration of 0.5 to 50 mg/litre exerted a genetic activity towards indicator microorganisms. The changes in the morphophysiological characteristics of yeast growth under the action of zineb are presumed to be of a protective nature. Zineb traces in soil must be controlled in terms of the microbiological index.

Drug Resistance, Microbial↗
PubMed1986

Fungicidal activity of murine inflammatory polymorphonuclear neutrophils: comparison with murine peripheral blood PMN.

A characteristic of inflammation is the influx of polymorphonuclear neutrophils (PMN) from peripheral blood to the inflammatory reaction. We report on metabolic alterations and alterations in fungicidal activity in PMN elicited intraperitoneally with different inflammatory agents. The fungicidal activity of murine peripheral blood PMN (PB-PMN) against phagocytosable Candida albicans and nonphagocytosable Blastomyces dermatitidis was compared to that of murine inflammatory PMN. PMN elicited with sodium caseinate exhibited enhanced killing of B. dermatitidis (93 +/- 3%) compared to PB-PMN (38 +/- 11.7%). In contrast, thioglycollate medium elicited PMN had significantly less ability to kill B. dermatitidis (3 +/- 5%) than PB-PMN. Incubation of caseinate PMN with thioglycollate medium for 1 h significantly reduced their ability to kill B. dermatitidis (95% vs 25%). This effect was not due to cytotoxicity of thioglycollate medium for PMN. Candidacidal activity of inflammatory PMN (caseinate or proteose peptone-elicited) was not significantly greater than that of peripheral blood PMN. However, inflammatory PMN had significantly greater candidacidal activity than thioglycollate-elicited PMN.

Animals↗