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

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O. Yu. Susova^1*, 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

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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.

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KEY WORDS: dimeric bisbenzimidazoles, topoisomerase I, inhibition

DOI: 10.1134/S0006297910060039

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