Design and Synthesis of 2-Methyl and 2-Methyl-4-Nitro Imidazole Derivatives as Antifungal Agents

Two series (a and b) of n-substituted heteroaromatic compounds related toclotrimazole were synthesized. imidazole ring of the clotrimazole was replaced by2-methylimidazole in series a, and by 2-methyl-4-nitroimidazole in series b. ocholortritylmoiety of clotrimazole was also replaced by trityl, mono or dimethoxytrityl. chemical structures of all the new compounds were confirmed by spectrophotometricmethods. these compounds docked into the active site of mt-cyp51(pdb code, 1e9x) using autodock tools software which showed good affinity forthe enzyme. antifungal activities of these compounds were evaluated againsttrichophyton mentagrophytes, microsporum gypseum and candida albicans usingsc, scc and pda as media, chcl3 and dmso as solvents and agar dilutionassay as method. in this method 1(4-methoxyphenyl-diphenylmethyl)-2-methylimidazole (2), 1[bis-4-methoxyphenyl-phenylmethyl]-2-methyl imidazole (3) and1[4-methoxyphenyl-diphenylmethyl]-2-methyl-4-nitroimidazole (5) showed morethan 75% activity against fungi. in the second step all of the derivatives also wereevaluated against trichophyton rubrum, microsporum canis and epidermaphytonfloccosum using pda medium by agar dilution method. compound 2 showed morethan 75% activity by this method. then the most active analogue (2) was tested inrpmi 1640 medium which showed desirable biological activity in comparison toclotrimazole.