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Minor Groove Dimeric Bisbenzimidazoles Inhibit in vitro DNA Binding to Eukaryotic DNA Topoisomerase I

O. Yu. Susova1*, A. A. Ivanov2, S. S. Morales Ruiz1, E. A. Lesovaya1, A. V. Gromyko2, S. A. Streltsov2, and A. L. Zhuze2

1Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, 115478 Moscow, Russia; fax: (495) 324-1205; E-mail: susovaolga@gmail.com

2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991 Moscow, Russia; fax: (499) 135-1405; E-mail: zhuze@imb.ac.ru; streltsov@eimb.ru

* To whom correspondence should be addressed.

Received November 30, 2009; Revision received December 14, 2009
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.
KEY WORDS: dimeric bisbenzimidazoles, topoisomerase I, inhibition

DOI: 10.1134/S0006297910060039