Occurrence of Conjugated Dienoic Fatty Acids in the Cellular Lipids of Pediococcus homari

Ninety-two thiolcarbamates with various substituents at the nitrogen and sulfur atoms, and their related compounds were synthesized, and their fungicidal activity against rice blast, Piricularia oryzae, and herbicidal activity against barnyardgrass, Echinochloa crus-galli, were determined in laboratory tests. The thiolcarbamate structure was necessary for the high fungicidal and herbicidal activities. The hydrophobicity of the substituents at the nitrogen atom was shown by the adaptive least-squares (ALS) method to be favorable to the fungicidal activity. The bulkier the substituents at the nitrogen atom, the less was the fungicidal activity. However, bulkiness of the substituents at the nitrogen and sulfur atoms was unfavorable to the herbicidal activity. The existence of a hydrogen atom at the nitrogen atom was favorable to fungicidal activity, but not to herbicidal activity. Correlation analyses were made to find compounds with both fungicidal and herbicidal activities against rice pests.     

INVESTIGATIONS ON FUNGICIDES. I. FUNGICIDAL AND SYSTEMIC FUNGICIDAL ACTIVITY IN CERTAIN ARYLOXYALKANECARBOXYLIC ACIDS

Fifty-four aryloxyalkanecarboxylic acids have been examined as systemic fungicides. Of these, four which produced negligible damage in broad-bean seedlings yet conferred systemic fungicidal protection to broad beans against Botrytis fabae and to tomatoes against Alternaria solanixvere studied in detail. The direct fungicidal activity of twenty compounds was assessed against B. fabae and Pythium ultimum. No correlation between fungicidal and systemic fungicidal action toward B. fabae was established. Other possibilities regarding their mode of action as systemic fungicides are discussed. The systemic fungicidal activity of a-phenoxyziobutyric and 2:4:6-trichlorophenoxyacetic acids in beans and of the latter compound in tomato plants was found to depend upon seasonal factors, but for 3-phenoxybutyric and 5-phenoxycaproic acids such variation was not observed. Results obtained in the bean test by two methods of assessment were found to correlate. The potato petiole test (van Raalte) for assessing systemic fungicidal activity was studied and modified. Evidence was obtained that the results might be unreliable owing to toxic effects produced by the compounds on the petiole tissue. Attempts were made to avoid this complication, but when phytotoxicity was eliminated, little fungicidal activity was shown.     

Evidence for chromosomal determination of fungicidal activity in strains of<Emphasis Type="Italic">Lactobacillus brevis</Emphasis> and<Emphasis Type="Italic">Lactobacillus fermentum</Emphasis> isolated from fermented foods

The genetic basis of the fungicidal activity of strains of Lactobacillus brevis and L. fermentum isolated from indigenous fermented foods was determined. A 5.5-kb plasmid was isolated from L. brevis while L. Fermentum was found to harbor no plasmid. Plasmid curing indicated no correlation between the plasmid and the fungicidal activity of the Lactobacillus species. The fungicidal activity of the isolated organisms can be supposed to be mediated by the chromosome. No antibiotic resistance genetic markers were detected on the plasmid and hence it was classified as cryptic.     

Design of novel peptide analogs with potent fungicidal activity,based on PMAP-23 antimicrobial peptide isolated from porcine myeloid

PMAP-23 is a 23-mer peptide derived from porcine myeloid. To develop novel antifungal peptides useful as therapeutic drugs, it would require a strong fungicidal activity against pathogenic fungal cells. To this goal, several analogs, with amino acid substitutions, were designed to increase the net hydrophobicity by Trp (W)-substitution at positions 10, 13, or 14 at the hydrophilic face of PMAP-23 without changing the hydrophobic helical face. The Trp (W)-substitution (P6) showed an enhanced fungicidal and antitumor activities, with the fungicidal activity inhibited by salts and the respiratory inhibitor, NaN(3). The results suggested that the increase of hydrophobicity of the peptides correlated with fungicidal activity. The fungicidal effects of analog peptides were further investigated using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a membrane probe. In Candida albicans, the analog peptide (P6) exerted its fungicidal effect on the blastoconidia in 20% fetal bovine serum by disrupting the mycelial forms. Furthermore, P6 caused significant morphological changes, and these facts suggested that the fungicidal function of the novel analog peptide (P6) was by damaging the fungal cell membranes. Thus, this peptide may provide a useful template for designing novel antifungal peptides useful for the treatment of infectious diseases.     

Structure and fungicidal activity of a synthetic antimicrobial peptide, P18, and its truncated peptides

P18 (KWKLFKKIPKFLHLAKKF-NH2) is an antimicrobial peptide designed from a cecropin A-magainin 2 hybrid that has potent antibacterial activity without hemolytic activity against human erythrocytes. In this study, P18 displayed potent fungicidal activity (MIC: 12.5 approximately 25 microM) against pathogenic fungi, Candida albicans, Trichosporon beigelii, Aspergillus flavus and Fusarium oxyspovrum. The central Pro9 residue and the entire sequence of P18 are essential for its full fungicidal activity. Circular dichroism analysis suggested that the higher alpha-helical content of the peptides did not correlate with the stronger fungicidal activity.     

The natural killer and fungicidal activity of the peripheral blood mononuclear cells in candidiasis

The activity of natural killers and the capacity of peripheral blood mononuclears for the extracellular killing of Candida cells in patients with different forms of candidiasis has been determined in the radiometric test with the use of targets labeled with 3H-uridine RNAase and in the fungicidal test. On the basis of the data thus obtained the conclusion has been made that in candidiasis changes in the activity of natural killers and fungicidal capacity depend on the severity of the disease and the stage of the process. Linear correlation between the activity of natural killers and fungicidal capacity in candidiasis patients at the stage of exacerbation and in healthy persons is absent.     

In vitro antifungal efficacy of ciclopirox olamine alone and associated with zinc pyrithione compared to ketoconazole against Malassezia globosa and Malassezia restricta reference strains

The aim of this study was to determine the in vitro fungicidal and growth inhibitory activity of ciclopirox olamine alone (1% and 1.5%) or in association with 1% zinc pyrithione compared to 2% ketoconazole, against Malassezia species particularly involved in the pathogenesis of seborrheic dermatitis. Experiments were performed on Malassezia globosa IP 2387.96 and M. restricta IP 2392.96 strains. Growth inhibitory activity of the active compounds in solution was evaluated by measuring minimal inhibitory concentrations using a broth micro-method and their fungicidal activity by a filtration method after contact times between solutions and yeasts ranging from 3–5 to 30 min. Concerning the determination of minimal inhibitory concentration of ciclopirox olamine/zinc pyrithione, it revealed the marked synergistic inhibitory effect of the association, leading to a higher efficacy compared to ketoconazole. As to the fungicidal activity of ciclopirox olamine, it significantly increased with the contact time. After 15–30 min of contact between 1.5% ciclopirox olamine and Malassezia strains, a 2-log reduction of Malassezia counts was observed. The 1.5% ciclopirox olamine/1% zinc pyrithione association was characterized by a steady fungicidal efficacy whereas the 2% ketoconazole solution did not express any fungicidal effect. In conclusion, this study demonstrates the in vitro inhibitory and fungicidal efficacy of the ciclopirox olamine/zinc pyrithione association against Malassezia species and underscores its potential interest in the treatment of seborrheic dermatitis.     

HP (2-20) derived from the amino terminal region of helicobacterpylori ribosomal protein L1 exerts its antifungal effects by damaging the plasma membranes of Candida albicans.

The fungicidal effects of the peptide HP (2-20). derived from the N-terminal sequence of Helicobacter pylori ribosomal protein L1 (RPL1). have been investigated. HP (2-20) displays a strong fungicidal activity against various fungi, without haemolytic activity against human erythrocyte cells, and the fungicidal activity is inhibited by Ca2+ and Mg2+ ions. In order to investigate the fungicidal mechanism(s) of HP (2-20). the amount of intracellular trehalose was measured in C. albicans. It was found that the amounts of intracellular trehalose were decreased when HP (2-20) was used. The action of the peptide against fungal cell membranes was further examined by the potassium-release test; HP (2-20) was found to increase the amount of K+ released from the cells. Furthermore, HP (2-20) caused significant morphological changes, as shown by scanning electron microscopy, and by testing the membrane disrupting activity using liposomes (phosphatidyl choline/cholesterol; 10: 1, w/w). Our results suggest that HP (2-20) may exert its antifungal activity by disrupting the structure of cell membranes, via pore formation or direct interaction with the lipid bilayers.     

Antifungal and fungicidal activities of tea extract and catechin against Trichophyton

We examined tea extract, (-) epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) for their antifungal and fungicidal activities against Trichophyton mentagrophytes, T. rubrum, Candida albicans and Cryptococcus neoformans. Tea extract (2.5%) inhibited completely the growth of both T. mentagrophytes and T. rubrum. EGCg at 2.5 mg/ml failed to inhibit their growth, whereas TF3 at 0.5 mg/ml inhibited the growth. EGCg (1mg/ml) showed no fungicidal activity against Trichophyton. TF3 (1mg/ml) killed Trichophyton by a long time contact (72-96 hrs). Tea extract showed a fungicidal activity against Trichophyton in a dose- and contact time-dependent manner. It did not inhibit the growth of C. albicans, but at a high concentration, inhibited slightly the growth of C. neoformans. It had no fungicidal activity against C. albicans or C. neoformans.     

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.     

Antimicrobial activity of some 2-amino-5-subsituted pyridine derivatives

A series of 2-amino-5-substituted pyridine derivatives were prepared and evaluated against phytopathogenic fungi and bacteria under laboratory conditions. Position 4 on the pyridine ring has notable fungicidal and bactericidal activity, greater than position 3 and/or position 6. Reaction of 1-hydroxymethyl benzotriazole with the amino group of the pyridine ring gave better fungicidal activity than substitution on the carbon of the pyridine ring (compound 4 versus 1c). Replacing the benzotriazole moiety with thiophenol exhibited the strongest fungicidal and bactericidal activity in this series (compound 3).     

Antimicrobial activity of [2-(methacryloyloxy)ethyl]trimethylammonium chloride against Candida spp

BackgroundCandida-associated denture stomatitis is the most common manifestation of oral candidal infection, caused mainly by Candida albicans. Several authors have attempted to add antifungal agents or antiseptics to denture temporary soft lining materials or to denture acrylic resins, without relevant results. Therefore, the investigation of a quaternary ammonium functionalized compound [2-(methacryloyloxy)ethyl]trimethylammonium chloride (MADQUAT), which copolymerizes with methacrylates and which could act as a fungal inhibitor, is of paramount importance.AimsTo evaluate the in vitro activity of MADQUAT against Candida species.MethodsThirty-one Candida strains were used to determine the in vitro antifungal activity of this compound. The minimum inhibitory concentrations and minimum fungicidal concentrations of MADQUAT and nystatin were determined.ResultsMADQUAT showed antifungal properties at concentrations of 6.25 to > 100 mg/ml, and fungicidal activity between 25 and > 100 mg/ml. The quantitative determinations of the fungistatic and fungicidal activity of MADQUAT showed fungistatic activity against all Candida albicans, Candida krusei and Candida parapsilosis strains, revealing fungicidal activity against some strains of the other species.ConclusionsMADQUAT has antifungal activity against Candida spp. Moreover, the sensitivity to this substance varies across the different species in terms of MIC values and fungicidal or fungistatic activity.     

Prostaglandin E2 inhibits Paracoccidioides brasiliensis killing by human monocytes

Human monocytes lacked fungicidal activity against high virulence strain of Paracoccidioides brasiliensis, even after IFN-gamma activation. However, monocytes treated with indomethacin exhibited an effective killing against this fungus, suggesting a role of prostaglandin E2 (PGE2) in the inhibition process. Thus, the purpose of this work was to determine whether the effect of PGE2 in fungicidal activity was related with decrease on H(2)O(2) release, the metabolite involved in P. brasiliensis killing, and changes in the levels of TNF-alpha, IL-6 and IL-10. Human monocytes challenged with the fungus produced high PGE2 levels, which in turn inhibited the fungicidal activity of these cells by reducing H(2)O(2) and TNF-alpha production.     

Lymphocyte-mediated modulation of the functional activity of macrophages by individual antigenic complexes of Trichophyton cells

The capacity of antigenic complexes of the causative agent of zoo- and anthroponotic trichophytosis for inducing the factors, that modify the functional activity of macrophages, in mice and in spleen cell cultures has been studied. These complexes are capable of inducing the T-lymphocyte-mediated suppression and of stimulating the fungicidal activity (and oxygen-dependent metabolism) of phagocytes. The production of fungicidal activity suppressing lymphokines is linked with the presence of alkali-insoluble components of fungal cell walls and cytoplasmic antigens (the latter appear only in interactions of antigens with the lymphocytes of immunized animals) in the above-mentioned complexes.     

Synthesis and fungicidal activity of 1-(alpha-tert-butylcinnamoyl)imidazoles

Several 1-(alpha-tert-butylcinnamoyl)imidazoles were prepared to examine their fungicidal activity. The (Z)-4-chlorocinnamoyl derivative was prepared from (anti)-2-tert-butyl-3-(4-chlorophenyl)-3-hydroxypropanoic acid by treating with 1,1'-carbonyldiimidazole and a subsequent beta-elimination reaction at an elevated temperature. The (Z)-isomer of the 4-chlorocinnamoyl derivative showed good fungicidal activity against Erysiphe graminis and Botrytis cinerea in pot tests, whereas the corresponding (E)-isomer derived from the (Z)-isomer through photoisomerization was much less active.     

Synthesis and biological activities of 2-oxocycloalkylsulfonamides

A series of novel 2-oxocycloalkylsulfonamides (4) were synthesized and their structures confirmed by IR, (1)H NMR, and elemental analysis. The bioassay showed that they have fair to excellent fungicidal activities against Botrytis cinerea Pers and Sclerotinia sclerotiorum. Among them, compounds 4A(10), 4A(11), 4A(12), 4B(2), and 4B(3), the EC(50) values of which were 2.12, 3.66, 3.96, 2.38, and 2.43 microg/mL, respectively, displayed excellent fungicidal activity against B. cinerea Pers, and are comparable with commercial fungicide procymidone (the EC(50) value is 2.45 microg/mL). 3D QSAR against B. cinerea Pers was studied, a statistically significant and chemically meaningful CoMFA model was developed and some compounds which have a high predicted activity were forecasted. In addition, the bioassay also showed that the compounds have good inhibitory activities against human tumor cells HL-60, BGC-823, Bel-7402 and KB. It is interesting to point out that the antitumor activities of compounds 4 are in accordance with their fungicidal activity to a great extent: compounds having relatively best antitumor activities (4A(10), 4A(11), 4A(12), and 4B(3)) also displayed excellent fungicidal activity.     

Interleukin-10 but not Transforming Growth Factor beta inhibits murine activated macrophages Paracoccidioides brasiliensis killing: Effect on H2O2 and NO production

Paracoccidioidomycosis is caused by the thermally dimorphic fungus Paracoccidioides brasiliensis (P. brasiliensis). Most often, this mycosis runs as a chronic progressive course affecting preferentially the lungs. In vitro fungicidal activity against a high virulent strain of P. brasiliensis by murine peritoneal macrophages preactivated with IFN-γ or TNF-α is high and correlates with increased NO and H₂O₂ production. Within this context, the purpose of this work was to study the role of suppressor cytokines, such as IL-10 and TGF-β, in this process. Incubation of either IFN-γ or TNF-α with IL-10 inhibits fungicidal activity of these cells. However, TGF-β had no effect on fungicidal activity of IFN-γ or TNF-α-activated macrophages. The suppression of fungicidal activity by IL-10 correlated with the inhibition of NO and H₂O₂ production supporting the involvement of these metabolites in P. brasiliensis killing. These results suggest that IL-10 production in vivo could represent an evasion mechanism of the fungus to avoid host immune response.     

Fungicidal Activity of N-Benzoylanthranilates and Related Compounds

Methyl N-(substituted benzoyl)anthranilates were found to possess inhibitory activity against the powdery mildew of cucumber caused by Sphaerotheca fuliginea. Both the anthranilate and the N-benzoyl moieties were essential for this type of fungicidal activity. Substitution at the 2- and 4-positions of the N-benzoyl group was unfavorable to the activity except for the 4-methoxy group. Substitution at the 3-position varied the fungicidal activity to various extents. The variation in the activity of 3-substituted derivatives was analyzed quantitatively with substituent parameters and regression analysis indicating that the variation in the steric dimension of substituents was most responsible for the activity.     

Synthesis and fungicidal activity of 2,2′-bipyridine derivatives

A series of substituted 2,2′-bipyridine derivatives was prepared using the Kröhnke reaction and alkylation of 4,4′-dimethyl-2,2′-bipyridine. These compounds were screened for fungicidal activity against 9 plant diseases. 5-Phenyl-2,2′-bipyridine exhibited strong preventative and curative fungicidal activity against wheat powdery mildew (Erisyphe graminis) and wheat leaf rust (Puccinia recondita).     

NK cells eliminate Cryptococcus neoformans by potentiating the fungicidal activity of macrophages rather than by directly killing them upon stimulation with IL-12 and IL-18

In the present study, we examined whether natural killer (NK) cells have direct fungicidal activity against Cryptococcus neoformans. Splenic NK cells were obtained from SCID mice and stimulated with a combination of interleukin (IL)-12 and IL-18 in flat culture plates or round tubes. They were then or at the same time cultured with the yeast cells and the number of viable yeast cells was examined. We could not detect direct fungicidal activity by NK cells under any culture condition, although they produced a large amount of IFN-gamma and exerted marked cytotoxic activity against YAC-1 cells. On the other hand, NK cells significantly potentiated the nitric oxide-mediated cryptococcocidal activity of thioglycolate-elicited peritoneal macrophages obtained from SCID mice upon stimulation with IL-12 and IL-18. The culture supernatants of NK cells stimulated with IL-12 and IL-18 provided similar results when used in place of NK cells. The induction of macrophage anticryptococcal activity by NK cells and NK cell culture supernatants were both mediated by IFN-gamma because the specific mAb almost completely abrogated such effect. Considered collectively, our results suggested that NK cells may play a regulatory role in potentiating macrophage-mediated fungicidal mechanisms in host resistance to infection with C. neoformans rather than exerting a direct killing activity against the fungal pathogen.