Design, synthesis, antileishmanial, and antifungal biological evaluation of novel 3,5‐disubstituted isoxazole compounds based on 5‐nitrofuran scaffolds

摘要: Nineteen 3,5-disubstituted-isoxazole analogs were synthesized based on nitrofuran scaffolds, by a [3 + 2] cycloaddition reaction between terminal acetylenes and 5-nitrofuran chloro-oxime. The compounds obtained in moderate to very good yields (45-91%). antileishmanial activity was assayed against the promastigote amastigote forms of Leishmania (Leishmania) amazonensis. Alkylchlorinated 14p-r active both forms, with emphasis compound 14p, which showed strong form (IC50  = 0.6 μM selectivity index [SI] = 5.2). In alkyl series, 14o stands out an IC50  = 8.5 μM SI = 8.0 form. aromatic most those containing electron-donor groups, such as trimethoxy isoxazole 14g  = 1.2 μM SI = 20.2); 14h,  = 7.0 μM SI = 6.1; 14j 4-SCH3 group,  = 5.7 μM SI = 10.2. addition, antifungal 19 isoxazoles evaluated five strains Candida (C. albicans, C. parapsilosis, krusei, tropicalis, glabrata). Eleven derivatives found be (minimal inhibitory concentration [MIC] = 3.4 μM) for this strain. Compound 14p all tested, MIC = 17.5 μM glabrata, lower than that fluconazole used reference drug.