The fungistatic activities of vitamin K on dermatophytes

Summary and conclusions Four commercial preparations of vitamin K were evaluated for their fungistatic activities on the following dermatophytes:Microsporum canis, Epidermophyton floccosum, Trichophyton mentagrophytes, andTrichophyton Schönleinii.Table 1 lists the maximum nonfungistatic and the minimum fungistatic concentrations of each vitamin K.The fungistatic activities of the vitamins K are higher in the liquid than in the solid medium.VitaminIV was the most active on all the dermatophytes in both, the solid and the liquid medium. The fungistatic activities of the other vitamins K vary, in each medium, according to the dermatophyte. Sodium bisulfite decreases the fungistatic activities of vitamin K. Epidermophyton floccosum was the most sensitive to all the vitamins K used.     

Susceptibility of Torulopsis glabrata in the presence of six antifungal agents determined by comparison of growth at several pHs

We describe a method using an automated system whereby fungistatic activities can be determined in several conditions. The process was adapted to Torulopsis glabrata, and it showed that benzalkonium chloride, chlorhexidine gluconate, and thimerosal preserve fungistatic activities in acidic medium, whereas acidification reduces the activity of povidone iodine and poloxamer.     

Effects of Pentachloronitrobenzene and Some of Its Known and Possible Metabolites on Fungi

Fungicidal activities of pentachloronitrobenzene and derivatives were tested with Candida albicans, Aspergillus fumigatus, Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporon canis. In relation to pentachloronitrobenzene, no increasing fungistatic activities were found with cysteine derivatives. Rising fungistatic activities were seen with pentachlorophenylmethylsulfone and, in some of the strains, with pentachloronitrosobenzene, pentachlorothiophenol, pentachlorophenol, pentachloroaniline, pentachlorophenylmethylsulfoxide, the isomeric tetrachloronitrobenzenes, tetrachlorothiophenols, tetrachlorophenols, and tetrachloroanilines.     

The fungistatic activity of ethylenic and acetylenic compounds; esters of halogenofumaric acids and acetylene dicarboxylic acid

A series of derivatives of acetylene dicarboxylic, halogenofumaric and related acids have been prepared and their fungistatic activities assessed. The lower halogeno- and thiocyanofumarates and acetylene dicarboxylates are highly fungistatic. The mode of action of these compounds is discussed.     

In vitro antifungal activities of anidulafungin and micafungin, licensed agents and the investigational triazole posaconazole as determined by NCCLS methods for 12,052 fungal isolates: review of the literature

The echinocandins anidulafungin and micafungin and the triazole posaconazole are currently undergoing phase III clinical trials. Caspofungin and voriconazole have recently been licensed for the treatment of aspergillosis (both agents), other less common mould (voriconazole) and candidal (caspofungin) infections. This review summarizes the published in vitro data obtained by NCCLS or NCCLS modified methods on the in vitro fungistatic and fungicidal activities of these five agents for yeasts and moulds in comparison to the established agents, amphotericin B, fluconazole, itraconazole, and flucytosine. Among the yeasts, the echinocandins have less activity for Candida parapsilosis and Candida guilliermondii, no activity for Cryptococcus neoformans and Trichosporon spp., but good fungistatic and fungicidal activity in vivo and in vitro for most of the other Candida spp.; this fungicidal activity has been reported by minimum fungicidal concentrations (MFCs) or time kill curve results. The new triazoles exhibit good fungistatic activity (but not fungicidal) for most Candida spp., C. neoformans, and Trichosporon spp. For the Aspergillus spp. evaluated, the echinocandins have similar or better fungistatic activity than those of amphotericin B and the triazoles, but fungicidal activity has been demonstrated only with amphotericin B and the triazoles, with the exception of fluconazole. Most studies showed posaconazole and voriconazole minimum inhibitory concentrations (MICs) ranging from 0.25 to 8 microg/ml for non-solani Fusarium spp., while MIC and minimum effective concentration (MEC) endpoints of the echinocandins were >8 microg/ml. The fungistatic activity of the triazoles is also superior to that of the echinocandins for most of the dimorphic fungi and the Zygomycetes. However, micafungin has activity for the mould phase of most dimorphic fungi, but not for the parasitic or yeast phase of Paracoccidioides brasiliensis. The echinocandins appear to have variable and species dependent fungistatic activity for the dematiaceous fungi, but all agents have poor or no activity against most isolates of Scedosporium prolificans. Only amphotericin B exhibit good fungistatic activity against the Zygomycetes. The combination of caspofungin with some triazoles, amphotericin B or liposomal amphotericin B has been synergistic in vitro, in animal models and in patients. Breakpoints are not available for any mould and antifungal agent combination. In vitro/in vivo correlations should aid in the interpretation of these results, but standard testing conditions are needed for the echinocandins, especially for mould testing, to obtain reliable results.     

Effects of pentachlorophenol and some of its known and possible metabolites on fungi.

The fungicidal activity of pentachlorophenol and its derivatives against 16 species of fungi representing 14 genera was tested. In relation to pentachlorophenol, no increase in fungistatic activity was found for pentachloroanisole, pentachloronitrobenzene, hexachlorobenzene, pentachlorophenyl acetate, o- and p-chloranil, the three isomeric chlorophenols, 2,6-dichlorophenol, the three isomeric tetrachlorobenzenediols, the three isomeric tetrachlorodimethoxybenzenes, the three isomeric tetrachlorobenzenediol diacetates, and all of the isomeric mono-, di-, tri-, and tetrachloroanisoles, except for 2,3,5-trichloroanisole with Geotrichum candidadum PC 67 and for 2,3,5,6-tetrachloroanisole with Mucor circinelloides PC 1. Increasing fungistatic activities were seen with 3,5-dichlorophenol, four trichlorophenols, and 2,3,4,5-tetrachlorophenol for all of the strains, with four dichlorophenols, 2,4,6-trichlorophenol, and two tetrachlorophenols for some strains, and with 2,3,6-trichlorophenol for only one strain (M. circinelloides PC 1).     

The fungistatic activity of ethylenic and acetylenic compounds; the effect of the affinity of the substituents for electrons upon the biological activity of ethylenic compounds

Over eighty compounds have been assayed for fungistatic activity. Fusarium graminearum, Penicillium digitatum and Botrytis allii were used as test organisms. The preliminary results suggest that fungistatic activity is associated with the tendency of the substituents to withdraw electrons from the double bond. Nitroethylenes and fumarates are, for example, fungistatic. Tetraiodoethylene has high activity but this can hardly be attributed solely to the withdrawal of electrons from the double bond by the iodine atoms.     

Fungistatic activity of different Indian soils againstFusarium udum Butler

Summary The fungistatic activity of different Indian soils againstF. udum, causing wilt disease of pigeon-pea, has been assessed in relation to soil pH and organic matter. Correlation co-efficient between soil characteristics and fungistasis has been calculated to evaluate relationship. High fungistatic activity was exhibited generally by the soils having low pH but high organic matter. The soils exhibiting high fungistatic activity againstF. udum have low incidence of wilt disease of pigeon-pea. There was no definite correlation between volatile and non-volatile fungistasis and, therefore, the origins of volatile and non-volatile fungistasis are different. In the usual biological limit pH had insignificant impact on fungistasis.     

N-Phenyl and N-phenylalkyl-maleimides acting against Candida spp.: time-to-kill, stability, interaction with maleamic acids

N-Phenyl and N-phenylalkyl maleimides (alkyl chain=(CH(2))n; n=0-4) and their respective open derivatives (maleamic acids) were evaluated against Candida spp. with the microbroth dilution method following the guidelines of CLSI (formely NCCLS). MIC values of maleimides without pre-incubation and submitted to different pre-incubation times into the growth media, time-to-kill studies as well as a time-dependent UV-spectroscopy study of the maleimides in water, led to determine that maleimides display antifungal activities with their intact maleimide ring, being in addition their activities not dependent on the length of the alkyl chain. They are not only fungistatic but fungicidal with very low MICs and MFCs, displaying strong fungicide activities not only against standardized but also clinical isolates of Candida albicans and non-albicans Candida spp.     

Fungistatic Intensity of Agricultural Soil Against Fungal Agents and Phylogenetic Analysis on the Actinobacteria Involved

A total of 287 agricultural soil samples collected from 26 provinces or autonomous regions of China were tested on their ability to suppress the conidial germination of nine biocontrol fungal agents. These soil samples showed great differences in the degree to inhibit the germination of conidia (22.8% < mean inhibition rate < 97.5%), but all exhibited fungistatic activities above the moderate levels (mean inhibition rate > 50%) to most of tested fungi. Ten soil samples that have stronger fungistatic intensity (germination inhibition rate > 68.3%) to the target fungi, Trichoderma viride and Paecilomyces lilacinus, were selected to evaluate their soil actinobacteria involved fungistasis in soil. Of the 1,000 isolates from those soil samples, 345 actinobacteria exhibited fungistatic activity to conidial germination of T. viride and P. lilacinus with germination inhibition rates higher than 10%. Sequences encoding 16S rRNA gene of the 345 actinobacteria were analyzed by ARDRA and resulted 44 different ARDRA types. Fifty-six isolates, at least one from each unique ARDRA type, were selected for 16S rDNA sequencing and phylogenetic analysis. Results indicated that the actinobacteria involved in the soil fungistasis had close phylogenetic relationship with the members of Sterptomycetaceae, Microbacteriaceae, Micrococcaceae, and Nocardiacea.     

Antifungal effects of the volatile oils from Allium plants against Trichophyton species and synergism of the oils with ketoconazole

In an attempt to develop stable and safe antifungal agents from natural products (daily foodstuffs in particular), the activities of essential oils from Allium sativum for. pekinense, A. cepa, and A. fistulosum against three Trichophyton species responsible for severe mycoses in humans were investigated and compared with activity of allicin in this study. The fungistatic activities of Allium oils were evaluated by the broth dilution method and disk diffusion assay. The combined effects of Allium oils with ketoconazole were tested by the checkerboard titer test. Among the tested oils, A. sativum for. pekinense oil exhibited the strongest inhibition of growth of T. rubrum, T. erinacei, and T. soudanense with MICs (minimum inhibiting concentrations) of 64microg/ml, while the activities of A. cepa and A. fistulosum were relatively mild. The inhibiting activities of the oils on Sabouraud agar plates were dose dependent against Trichophyton species. Additionally, these oils showed significant synergistic antifungal activity when combined with ketoconazole in the checkerboard titer test and disk diffusion test.     

Fungistatic Effects of Controlled Atmospheres

The fungistatic effects of controlled atmospheres composed of increased CO(2) and decreased O(2) was studied in a manner such that the condition of stored fruit was not a factor in the growth of the fungi. Varying concentrations of O(2) and CO(2) were used. The fungi used were Botrytis alli, Rhizopus nigricans, and Penicillium expansum. The results showed that controlled atmospheres, within the limits of concentrations usable for fruit storage, are effective fungistatic agents.     

The fungistatic activity of ethylenic and acetylenic compounds; the fungistatic activity of tetraiodoethylene and related compounds

The high fungistatic activity of tetraiodoethylene has been investigated. Diiodo-acetylene, which like tetraiodoethylene is an unsaturated substance containing only carbon and iodine, has also been found to have a high antifungal action. The effect of replacing the iodine atoms in these compounds by hydrogen, bromine, and carboxyl and nitro groups has been studied. The high fungistatic activity of some iodoethylenic and iodoacetylenic compounds appears to be associated with the presence in the molecule of positive iodine.     

Antifungal activity displayed by cereulide, the emetic toxin produced by Bacillus cereus

In this study, the fungistatic activity of Bacillus cereus cereulide-producing strains was demonstrated against nine fungal species. The role of cereulide was confirmed using plasmid-cured derivatives and ces knockout mutants. The fungistatic spectra of cereulide and valinomycin, a chemically related cyclododecadepsipeptide, were also compared and found to be similar but distinct.     

Effect of the antiseptic merthiolate and its derivatives on fungi causing deterioration

The fungistatic activity of merthiolate and its two polymerous derivatives have been investigated using as test cultures fungi producing deterioration. The fungicides sorbtion dynamics by the fungus micelium have been studied, toxicity and inhibition rate of the catalase from different sources have been evaluated. The polymerous derivatives have been found to maintain high fungistatic activity of merthiolate, but possess less toxicity. The sorbtion of the polymerous derivative by the fungal mycelium takes place more effectively than the merthiolate sorbtion. The probable reasons of the high activity of the merthiolate polymerous derivatives are under discussion.     

Lovastatin possesses a fungistatic effect against Candida albicans, but does not trigger apoptosis in this opportunistic human pathogen

Lovastatin inhibited the growth of Candida albicans in a fungistatic way. Although it triggers apoptosis in a great variety of eukaryotic cells, including many tumour cell lines, lovastatin failed to provoke apoptotic events in this human pathogen. The fungistatic behaviour of this statin might arise from its negative influence on membrane fluidity. Because yeast-->pseudomycelium and hyphae morphogenetic transitions took place under exposure to lovastatin morphogenetic switch and apoptotic cell death must be regulated independently in C. albicans.     

Probiotic Lactobacillus and Bifidobacterial Lectins Against Candida albicans and Staphylococcus aureus Clinical Strains: New Class of the Pathogen Biofilm Destructors

Preparations of probiotic bifidobacterial and lactobacillus lectins possessed system affinity to mannan and mucin-type polymers. It was shown that these lectins possess fungistatic and fungicidal activities against nystatin-resistant Candida albicans clinical strains. Lectins revealed destructive properties with respect to C. albicans and Staphylococcus aureus biofilms, depending on clinical strain origin and lectin preparation type. Synergistic antipathogen activities between lectins and between lectins and nystatin were observed. In the presence of lectins, pathogen biofilm degradation occurred in sequential steps, including biofilm refinement, appearance of edge cavities, segmentation, detachment of fragments and their lysis. Fungal response to lectins was more complex compared to that of staphylococci. Cold stress improved pictures of lectin antipathogen action. The data indicate that probiotic bacterial lectins are members of a new class of antimicrobials—destructors of pathogen biofilms.     

Studies on the Phenylphenol Derivatives with Biological Activity

More than ninety phenylphenol derivatives were tested for fungistatic activity toward ten species of agriculturally important fungi. One of N-methylcarbamates and some nitro- or chloro-substituted derivatives were highly toxic against Piricularia oryzae. From the relationship between the chemical structure and the activity, it is supposed that the reactivity, the permeability, the steric effect and the metabolic activation of the compound are the responsible factors for the fungistatic activity.     

INVESTIGATIONS ON FUNGICIDES. III. THE FUNGITOXICITY OF 3- AND 5-ALKYL-SALICYLANILIDES AND PARA-CHLOROANILIDES

The anilides and para -chloroanilides have been prepared from the first four homologues of the 3- and 5-alkylsalicylic acid series and the fungistatic activity of these compounds has been assessed by two methods. In tests against mycelium, the chloroanilides usually induced less retardation of growth than the corresponding anilides. The effect of introducing an alkyl grouping was in general to reduce the fungistatic effect but with the n -propyl derivatives this trend was less marked. Salicylanilide gave the greatest over-all inhibition of the fungi investigated.     

FUNGICIDAL ACTIVITY AND CHEMICAL CONSTITUTION

A series of 5- n -alkyl oxines was tested against the mycelium of Aspergillus niger. As non-chelated molecules, they showed maximum fungistatic activity at a chain length of 5–6 carbon atoms. Values of Ferguson's thermodynamic activity coefficient, obtained from spore germination tests with Sclerotinia laxa , indicated that the mechanism of toxicity of the lower homologues is predominantly chemical, whilst that of the n -amyl and higher members is mainly physical.
The ED 50 value of 5- n -amyl-6-hydroxyquinoline, which is incapable of chelation, was found to be eighty times greater than that of 5- n -amyl oxine (in the non-chelated form). The optimum initial pH for fungistatic activity of the latter was 5.4–5.6.
In the presence of metals the pattern of fungistatic activity was markedly altered: maximum activity in the presence of Cu²⁺, Fe²⁺and Zn²⁺was found with oxine and 5-methyloxine.