Synthesis and anticandidal activity of azole-containing sulfonamides

Twenty five benzenesulfonamides containing one imidazole or triazole ring, or two imidazole or triazole rings have been synthesized and evaluated as anticandidal agents. The most active compounds were 5c, 6b, 6c, 6e, and 17b, which exhibited MIC values of 4.5 5 - 24.39 mM depending on the clinical isolate. Comparing imidazole to triazole derivatives did not show a clear effect on activity. Compounds containing a N-benzyl group also showed no clear evidence on activity given the fact that they have an extra aromatic ring. Secondary sulfonamides, 5l, 5m, and 5n showed activities that were proportional to their lipophilicity. The activities of N-aryl-substituted derivatives 5j, 5k, 5l, 5m, 5n, and 6j were also proportional to their lipophilicity. Halogenation enhanced the activity as a result of improvement of lipophilicity. The presence of two imidazole or triazole rings in the same compound did not show a clear enhancement of activity.