Effect of 5-Nitro and 5-Chloro Benzimidazole Derivatives on Heme Synthesis in vitro ∗

Abstract

Summary

5-Nitro-, 2-methyl-5-nitro-, and 2-ethyl-5-nitrobenzimidazole; 5-chloro-, 2-methyl-5-chloro-, and 2-ethyl-5-chlorobenzimidazole were prepared and their effects on incorporation of N¹⁵ from N¹⁵-glycine into heme by chicken erythrocytes incubated in vitro were studied. Similar to the 5-methyl-benzimidazole series studied previously, the 2-ethyl-5-nitro- was considerably more inhibitory than the 5-nitro- or 2-methyl-5-nitro-benzimidazole. Likewise in the 5-chloro series, 2-ethyl-5-chloro- was considerably more inhibitory than the 5-chloro- or 2-methyl-5-chlorobenzimidazole. 5-Chloro derivatives appeared to be more inhibitory than the corresponding 5-nitro analogues; 2-ethyl-5-chlorobenzimidazole was as effective as 2-ethyl - 5 - methylbenzimidazole, whereas 2-ethyl-5-nitrobenzimidazole was not. All were more effective than benzimidazole itself. Although methyl, chloro or nitro groups in the 5 position gave compounds having inhibitory activity greater than that of unsubstituted benzimidazole, 5-hydroxybenzimidazole was comparatively ineffective.