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

Abstract The synthesis and some germicidal activities in vitro of two congener series of S-substituted 4,6-dihalogeno-2-mercapto-1 H -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 μg/ml for Gram-positive bacteria. The most active compounds (MICs for Gram-positive bacteria: 0.78–50 μg/ml) were 4,6-dichloro-2-(4-nitrobenzylthio)-1 H -benzimidazole and 4,6-dibromo-2-(4-nitrobenzylthio)-1 H -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 ≤100 μg/ml), whereas Pseudomonas aeruginosa was most resistant to the new benzimidazole derivatives (all MICs >400 μg/ml). All the new compounds were at least several times more active against Giardia intestinalis (IC 50 : 0.006–0.053 μg/ml), and a half of them were at least several times more active against Trichomonas vaginalis (IC 50 : 0.0015–0.182 μg/ml) than metronidazole (IC 50 : 0.210 and 0.037 μg/ml, respectively), the drug of choice in the treatment of G. intestinalis and T. vaginalis infections.