Minor groove dimeric bisbenzimidazoles inhibit in vitro DNA binding to eukaryotic DNA topoisomerase I

O Yu Susova; A A Ivanov; S S Morales Ruiz; E A Lesovaya; A V Gromyko; S A Streltsov; A L Zhuze

doi:10.1134/s0006297910060039

Minor groove dimeric bisbenzimidazoles inhibit in vitro DNA binding to eukaryotic DNA topoisomerase I

Biochemistry (Mosc). 2010 Jun;75(6):695-701. doi: 10.1134/s0006297910060039.

Authors

O Yu Susova¹, A A Ivanov, S S Morales Ruiz, E A Lesovaya, A V Gromyko, S A Streltsov, A L Zhuze

Affiliation

¹ Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia. susovaolga@gmail.com

PMID: 20636260
DOI: 10.1134/s0006297910060039

Abstract

The potential of six dimeric bisbenzimidazoles bound to scDNA to inhibit eukaryotic DNA topoisomerase (topo-I) was studied chemically; the tested compounds differed in linker structure and length. All the compounds inhibited topo-I, DB(7) being the most efficient; its inhibitory activity in vitro was 50-fold higher than that of camptothecin. It is noteworthy that inhibitory properties of nearly all the tested compounds increased many times if they were preincubated with scDNA for three days.

Publication types

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

MeSH terms

Bisbenzimidazole / chemistry
Bisbenzimidazole / pharmacology*
DNA / metabolism*
DNA Topoisomerases, Type I / metabolism*
Dimerization
Protein Binding
Topoisomerase I Inhibitors

Substances

Topoisomerase I Inhibitors
DNA
DNA Topoisomerases, Type I
Bisbenzimidazole