FUNGICIDAL ACTIVITY AND CHEMICAL CONSTITUTION:

Nine derivatives of pentachlorophenol have been prepared and tested for fungistatic activity against the mycelia of Botrytis fabae, Sclerotinia laxa and Stereum purpureum and for phytotoxicity towards tomato, apple and plum. The most fungitoxic of these compounds was the acetyl ester. Its phytotoxicity, although much less than that of pentachlorophenol itself, nevertheless precludes its effective use as an eradicant fungicide on foliage.     

INVESTIGATIONS ON FUNGICIDES II. ARYLOXY- AND ARYLTHIO-ALKANECARBOXYLIC ACIDS AND THEIR ACTIVITY AS FUNGICIDES AND SYSTEMIC FUNGICIDES

A wide range of aryloxyacetic acids and corresponding acids with alkyl groups in the side chain, their arylthio- analogues and the antibiotic griseofulvin have been assessed in the plate test for fungistatic effect on six fungi, and as systemic fungicides against Botrytis fabae in broad beans and Alternaria solani in tomatoes. The results indicate that in general, arylthio- derivatives are more fungicidal than their aryloxy- analogues. The systemic fungicidal performance of x-(2-chlorophenylthio)propionic acid in the tomato test at 1–100 p. p. m. was found to be of the same order as that shown by griseofulvin at 50–500 p. p. m. Variable results were obtained with griseofulvin in the tornato test and its performance in the bean test was consistently poor. Further evidence is presented which indicates that the protection conferred by certain compounds may not be due to activity per se .     

Effect of fatty acid anilides on the generation of arachidonic acid by human polymorphonuclear leukocytes

The addition of oleoylanilide or linoleylanilide to human polymorphonuclear leukocytes induces a time- and dose-dependent generation of arachidonic acid. Half-maximal effect is caused by a dose of 0.2 mg linoleylanilide/ml. Fatty acid anilides also produce a time- and dose-dependent inhibition of the synthesis of triacylglycerol. Half-maximal effect is caused by 1 microgram linoleylanilide/ml. These results indicate that fatty acid anilides, which have been found in the illegal cooking oil which intoxicated thousands of Spaniards, alter lipid metabolism in human polymorphonuclear leukocytes.     

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.     

Lasiodiplodia theobromae as a cause of keratomycoses.

Four cases of human keratitis caused by the tropical fungus Lasiodiplodia theobromae have been encountered in Miami, Florida bringing to 8 the number of cases reported in the world literature. Two of the ulcers were mild. Three patients recovered without severe impairment of vision after topical polyene treatment, but 1 patient with a severe ulcer required therapeutic keratoplasty after 11 days of topical natamycin. Histopathology revealed fungus deep in the cornea, invading Descemet's membrane. L. theobromae appeared to have collagenase activity in vitro. Inoculation of L. theobromae into the corneas of rabbits produced progressive ulcers. The fungus was endemic in Miami on home grown and imported bananas. Polyene antimycotic antibiotics were fungicidal for L. theobromae in vitro. Thiabendazole was effectively fungistatic but varied in fungicidal effect. Clotrimazole and miconazole were only incompletely fungistatic. Of 7 strains of L. theobromae tested, 4 were relatively resistant to 5-flurocytosine.     

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.     

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.     

Killer toxin of Kluyveromyces phaffii DBVPG 6076 as a biopreservative agent to control apiculate wine Yeasts.

The use of Kluyveromyces phaffii DBVPG 6076 killer toxin against apiculate wine yeasts has been investigated. The killer toxin of K. phaffii DBVPG 6076 showed extensive anti-Hanseniaspora activity against strains isolated from grape samples. The proteinaceous killer toxin was found to be active in the pH range of 3 to 5 and at temperatures lower than 40 degrees C. These biochemical properties would allow the use of K. phaffii killer toxin in wine making. Fungicidal or fungistatic effects depend on the toxin concentration. Toxin concentrations present in the supernatant during optimal conditions of production (14.3 arbitrary units) exerted a fungicidal effect on a sensitive strain of Hanseniaspora uvarum. At subcritical concentrations (fungistatic effect) the saturation kinetics observed with the increased ratio of killer toxin to H. uvarum cells suggest the presence of a toxin receptor. The inhibitory activity exerted by the killer toxin present in grape juice was comparable to that of sulfur dioxide. The findings presented suggest that the K. phaffii DBVPG 6076 killer toxin has potential as a biopreservative agent in wine making.     

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.     

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.     

土壤抑菌作用对食线虫真菌及其制剂的影响*

通过我国东北及黄淮海地区主要大豆种植区11种土壤对4株定殖于大豆胞囊线虫真菌淡紫拟青霉（Paecilomyceslilacimus）M-14,厚垣孢子轮枝菌（Verticilliumchlamydosporium）JN-11SH-26和BQL－1孢子的抑制作用及其影响因子的研究,表明土壤抑菌作用普遍存在,但依土壤条件、菌种类型而异,其中以安徽宿县、济南农科院、北京、黑龙江宝泉岭农场的土壤抑菌作用最强,洗涤悬液中孢子萌发率多小于30％,济南敬家、河南开封、黑龙江八五三农场等地土壤抑菌现象不明显,孢子萌发率一般在40～80％。同一土壤对4个菌株的影响是一致的。将菌种液体发酵培养,其滤液孢子萌发率一般可提高至50％以上。加入复合添加剂制得菌剂后,孢子萌发率进一步提高。土壤中微生物数量对其抑菌作用的强弱有很大影响。一般来说土壤中微生物数量越多,抑菌作用表现得也越明显。机理探讨表明土壤中存在着一些水溶性及挥发性的抑制因子,其中水溶性成分是主导因素。     

Soil fungistasis: role of the microbial nutrient sink and of fungistatic substances in two soils.

Sensitivity of conidia of Cochliobolus victoriae to fungistasis decreased markedly following incubation on moist sand for at least 1 h. Germination was greater on Conover loam or on sand being leached with water than on an alkaline clay loam soil known to produce a volatile fungistatic substance. Evolution of 14CO2 began within 3 min after [14C]glucose was applied to the soils; the rate of 14CO2 evolution was faster with Conover loam. Germination of Thielaviopsis basicola conidia per unit of glucose remaining in agar discs initially containing 0-1% glucose, was lower for discs incubated on the clay loam soil than on Conover loam, and was greatest on a bed of sand undergoing aqueous leaching. Germination of ascospores of Neurospora tetrasperma and conidia of C. victoriae was suppressed on discs of washed, Purified Agar or polyacrylamide gel incubated on or over the clay loam soil, but no suppression resulted when discs were incubated on Conover loam. Extensive aeration of either soil did not remove its fungistatic effect. Fungistasis in Conover loam appears to be caused primarily by nutrient deprivation, whereas volatile fungistatic substances may play a major role in the clay loam soil.     

Mixtures of Quaternary Ammonium Compounds and Long-chain Fatty Acids as Antifungal Agents

The influence of undecylenic acid on the fungistatic effect of phenoxyethyldimethyldodecylammonium bromide (Domiphen bromide) against Trichophyton mentagrophytes was investigated. The unsaturated fatty acid was found to enhance the fungistatic activity of Domiphen bromide against this organism. The ratio of concentrations of these agents has a marked influence on the results of in vitro tests for antifungal action resulting in a completely different effect than heretofore noted in combination experiments against bacteria. The enhancing phenomenon is not particular to T. mentagrophytes, it was observed also with Candida albicans.     

Fungistatic and fungicidal effects of the ionophores monensin and tetronasin on the rumen fungus Neocallimastix sp. LM1

The ionophore antibiotics monensin and tetronasin have been reported to inhibit anaerobic fungi in vitro, and are suitable for animal use. In this study, their effectiveness in removing the anaerobic fungus Neocallimastix sp. LM1 from the rumen was investigated in vitro. Both antibiotics were fungistatic: tetronasin at 0.5 microgram/ml and monensin at 1.0 microgram/ml; exposure for 24 h did not inhibit subsequent growth after removal of the ionophore. The ionophores were fungicidal at much higher concentrations, 1 microgram/ml for tetronasin and 16 micrograms/ml for monensin. It seems likely that the combination of relatively high inhibitory dose and the fungistatic nature of monensin would explain difficulties in using this compound to eliminate anaerobic fungi from the rumens of experimental animals.     

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.     

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.     

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.     

Effect of liming on spore germination,germ tube growth and root colonization by vesicular-arbuscular mycorrhizal fungi

Summary The effect of soil acidity on spore germination, germ tube growth and root colonization of vesicular-arbuscular mycorrhizal (VAM) fungi was examined using a Florida Ultisol. Soil samples were treated with 0, 4, 8 and 12 meq Ca/MgCO₃/100 g soil and each lime level received 0, 240, and 720 ppm P as superphosphate. Corn (Zea mays L.) was planted in the soil treatments, inoculated with eitherGlomus mosseae orGigaspora margarita spores and grown for 31 days. Acid soil inhibits mycorrhizal formation byG. mosseae through its strong fungistatic effect against the spores. The dolomitic lime increased mycorrhizal formation by both fungal species.G. margarita is much less sensitive to acidic conditions thanG. mosseae. Al ions are a very important component of the fungistatic property against the VAM symbiosis. VAM fungus adaptation may be important for plants growing on infertile acid soils if soil inoculation with these fungi is to contribute significantly to low-input technology for tropical agricultural systems.     

Toxic effects of fatty acid anilides on the oxygen defense systems of guinea pig lungs and erythrocytes

Toxic oil syndrome (TOS) is caused by ingestion of denatured edible oils. Even though the etiology and pathogenesis of this disease are not fully known, it is quite clear that generation of free radicals caused by ingestion of fatty acid anilides is responsible for the pathogenetic mechanism in many TOS patients. Fatty acid anilides may also alter the free radical status of lungs and erythrocytes; this possibility may shed some light on understanding toxic oil syndrome. The present study describes the effects of oral administration of fatty acid anilides on the activities of major enzymes involved in the oxygen defense systems of lungs and erythrocytes. Feeding fatty acid anilides caused an increase in the superoxide dismutase (SOD) activity in erythrocytes, whereas it caused a decrease in the SOD activity in lungs. GSH-Px activity was not significantly changed in erythrocytes but was decreased in lungs. Although the activity of catalase was increased only by a higher dose in the erythrocytes, it was not affected in the lung at any dosage. Even though the ingestion of fatty acid anilides caused an increase in the SOD activity in the erythrocytes and a decrease in the SOD activity in the lungs, there was an increase in the lipid peroxidation in both cases. The increase in lipid peroxidation in erythrocytes is probably caused by the accumulation of H₂O₂, and that in the lungs is due to the accumulation of superoxide anion.     

Biotransformation of the fungistatic sesquiterpenoids patchoulol, ginsenol, cedrol and globulol by Botrytis cinerea

The antifungal activity of natural sesquiterpenoids patchoulol, ginsenol, cedrol and globulol against the fungus Botrytis cinerea has been determined. The diminishing of the effect after 3–6 days suggests that a mechanism of detoxification is present. Biotransformation of these fungistatic compounds has been investigated as a method of studying this mechanism.