Scroferneker M.L., Rosa D, Ricardo S, Dornelles L, Corbellini V

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Introduction: 1, 2, 4-oxadiazole derivatives belong to a group of compounds whose synthesis and application for inhibition of microbial growth has been widely explored. The genus Bipolaris consists of a group of characteristically phytopathogenic dematiaceous fungi that are ubiquitous in the environment, and which opportunistically affect the human host and cause phaeohyphomycosis. Drug therapies include itraconazole. Objective: the aim of this study was to assess the antifungal potential of a new class of heterocyclic compounds, based upon the 1,2,4-oxadiazole system modified at position 5, with amino acid derivatives in a sample of Bipolaris sorokiniana as representative of a phaeohyphomycotic agent. Material and methods: 1, 2, 4-oxadiazole derivatives EC, FC, EA and FA were obtained by condensation of benzamidoxime or p-chlorobenzamidoxime and L-cysteine or L-phenylalanine, respectively. Tricyclazole was used as standard drug. Antifungal activity was determined by the modified Butty method. The inoculum was prepared with 3-mm discs of 15-day culture on Petri dishes containing Sabouraud agar. The discs were inversely placed (culture in contact with the agar) onto plates containing 9.9mL of Sabouraud agar, and received 0.1mL of solutions 2.0, 1.0, 0.5, 0.25, 0.125, 0.0625 and 0.0x10-3M of the drugs diluted in dimethyl sulfoxide. After 3-day incubation at 30°C, colony diameters were determined and compared with the concentration and nature of the 1, 2, 4-oxadiazole derivative. Results: All compounds showed antifungal activity; however, their behavior varied. The microorganism produced a different response between the group of 1, 2, 4-oxadiazoles and tricyclazole. The standard drug showed a higher antifungal activity in the high-concentration region. EC had maximum activity at 0.1M, while the maximum activity of FC occurred at 2x10-3M. Microorganism activity was different between the group of 1, 2, 4-oxadiazoles and tricyclazole. EA had a fluctuating curve, where the concentrations with higher activity ranged from 0.0625 to 0.125x10-3M. FA produced a parabolic curve and showed a stimulating effect. EC was more powerful than FC, which shows that chlorine does not have an effect on the properties of the tested compounds. By comparing the activities of EC and FC, we observed that EC was more powerful, showing that L-cysteine was more powerful than L-phenylalanine, which means that sulfur influences antifungal power. The MICs for tricyclazole, EC, FC, EA, and FA were respectively 2.0, 1.0, 2.0, 0.0625, and 2.0x10-3M. The derivatives did not produce changes to mycelial pigmentation when compared to tricyclazole, which indicates that they might not operate on the cytochrome P450 oxidase system involved in DHN melanin production. Conclusion: 1, 2, 4-oxadiazoles showed to be versatile molecules and to produce different results for distinct functions of the ring, thus confirming their potential use as antifungal drugs against Bipolaris sorokiniana. Supported by Fapergs.

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The 15 th Congress of the International Society for Human and Animal Mycology
    • ISHAM 15th (2003)