Synthesis, and antiprotozoal and antibacterial activities of S-substituted 4,6-dibromo- and 4,6-dichloro-2-mercaptobenzimidazoles

The synthesis and some germicidal activities in vitro of two congener series of S-substituted 4,6-dihalogeno-2-mercapto-1H-benzimidazoles are reported. There was no substantial difference between antibacterial activities of corresponding 4,6-dichloro- and 4,6-dibromo-derivatives. The present results confirm lower susceptibility to substituted benzimidazoles of Gram-negative compared to Gram-positive bacteria. Minimum inhibitory concentrations (MICs) of a majority of the novel derivatives ranged between 25 and 100 mug/ml for Gram-positive bacteria. The most active compounds (MICs for Gram-positive bacteria: 0.78-50 mug/ml) were 4,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole and 4,6-dibromo-2-(4-nitrobenzylthio)-1H-benzimidazole that were 4-32 times more potent than nitrofurantoin against all Gram-positive bacteria utilized but Escherichia faecalis, against which they were, respectively, 2 and 4 times less potent than nitrofurantoin. Among Gram-negative bacteria used, Stenotrophomonas maltophilia and Bordetella bronchiseptica were most sensitive (as evidenced by a number of MICs less than or equal to 100 mug/ml), whereas Pseudomonas aeruginosa was most resistant to the new benzimidazole derivatives (all MICs > 400 mug/ml). All the new compounds were at least several times more active against Giardia intestinalis (IC50: 0.006-0.053 mug/ml), and a half of them were at least several times more active against Trichomonas vaginalis (IC50: 0.0015-0.182 mug/ml) than metronidazole (IC50: 0.210 and 0.037 mug/ml, respectively), the drug of choice in the treatment of G. intestinalis and T. vaginalis infections. (C) 2003 Elsevier B.V. All rights reserved.