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Selective Inhibition of Bacterial Topoisomerase I by alkynyl-bisbenzimidazoles.

ABSTRACT: Hoechst dyes are well known DNA binders that non-selectively inhibit the function of mammalian topoisomerase I and II. Herein, we show that Hoechst 33258 based bisbenzimidazoles (DPA 151-154), containing a terminal alkyne, are effective and selective inhibitors of E. coli. topoisomerase I. These bisbenzimidazoles displayed topoisomerase I inhibition much better than Hoechst 33342 or Hoechst 33258 with IC50 values in the range of 2.47-6.63 ?M. Bisbenzimidazoles DPA 151-154 also display selective inhibition of E. coli. topoisomerase I over DNA gyrase and Human topoisomerases I and II, and effectively inhibit bacterial growth.

SUBMITTER: Ranjan N

PROVIDER: S-EPMC4112416 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Selective Inhibition of Bacterial Topoisomerase I by alkynyl-bisbenzimidazoles.

Ranjan Nihar N Fulcrand Geraldine G King Ada A Brown Joseph J Jiang Xiuping X Leng Fenfei F Arya Dev P DP

MedChemComm 20140601 6

Hoechst dyes are well known DNA binders that non-selectively inhibit the function of mammalian topoisomerase I and II. Herein, we show that Hoechst 33258 based bisbenzimidazoles (DPA 151-154), containing a terminal alkyne, are effective and selective inhibitors of E. coli. topoisomerase I. These bisbenzimidazoles displayed topoisomerase I inhibition much better than Hoechst 33342 or Hoechst 33258 with IC50 values in the range of 2.47-6.63 μM. Bisbenzimidazoles DPA 151-154 also display selective ...[more]

PMID: 25083189

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