Dimeric bisbenzimidazoles inhibit the DNA methylation catalyzed by the murine Dnmt3a catalytic domain

N A Cherepanova; A A Ivanov; D V Maltseva; A S Minero; A V Gromyko; S A Streltsov; A L Zhuze; E S Gromova

doi:10.3109/14756366.2010.499098

Dimeric bisbenzimidazoles inhibit the DNA methylation catalyzed by the murine Dnmt3a catalytic domain

J Enzyme Inhib Med Chem. 2011 Apr;26(2):295-300. doi: 10.3109/14756366.2010.499098. Epub 2010 Jul 8.

Authors

N A Cherepanova¹, A A Ivanov, D V Maltseva, A S Minero, A V Gromyko, S A Streltsov, A L Zhuze, E S Gromova

Affiliation

¹ Chemistry Department, Moscow State University, Moscow, Russian Federation.

PMID: 20615081
DOI: 10.3109/14756366.2010.499098

Abstract

When located in the DNA minor groove, dimeric bisbenzimidazoles DB(n) effectively inhibited in vitro the Dnmt3a catalytic domain (IC₅₀ 5-77 μM). The lowest IC₅₀ value was observed for compound DB(11) with an 11-unit methylene linker joining the bisbenzimidazole fragments. Increased time of incubation of DNA with DB(n) as well as the presence of AT-clusters in DNA enhances the inhibitory effect.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bisbenzimidazole / chemical synthesis
Bisbenzimidazole / chemistry
Bisbenzimidazole / pharmacology*
Catalytic Domain
DNA Methylation / drug effects*
DNA Modification Methylases / chemistry*
DNA Modification Methylases / metabolism*
Magnetic Resonance Spectroscopy
Mice
Molecular Structure

Substances

DNA Modification Methylases
Bisbenzimidazole