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Inhibition of human DNA topoisomerase II? by two novel ellipticine derivatives.

ABSTRACT: Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is an antineoplastic agent that intercalates into DNA and alters topoisomerase II activity. Unfortunately, this compound displays a number of adverse properties. Therefore, to investigate new ellipticine-based compounds for their potential as topoisomerase II-targeted drugs, we synthesized two novel derivatives, N-methyl-5-demethyl ellipticine (ET-1) and 2-methyl-N-methyl-5-demethyl ellipticinium iodide (ET-2). As determined by DNA decatenation and cleavage assays, ET-1 and ET-2 act as catalytic inhibitors of human topoisomerase II? and are both more potent than the parent compound. Neither compound impairs the ability of the type II enzyme to bind its DNA substrate. Finally, the potency of ET-1 and ET-2 as catalytic inhibitors of topoisomerase II? appears to be related to their ability to intercalate into the double helix.

SUBMITTER: Vann KR

PROVIDER: S-EPMC4785065 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Inhibition of human DNA topoisomerase IIα by two novel ellipticine derivatives.

Vann Kendra R KR Ergün Yavuz Y Zencir Sevil S Oncuoglu Serkan S Osheroff Neil N Topcu Zeki Z

Bioorganic & medicinal chemistry letters 20160215 7

Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is an antineoplastic agent that intercalates into DNA and alters topoisomerase II activity. Unfortunately, this compound displays a number of adverse properties. Therefore, to investigate new ellipticine-based compounds for their potential as topoisomerase II-targeted drugs, we synthesized two novel derivatives, N-methyl-5-demethyl ellipticine (ET-1) and 2-methyl-N-methyl-5-demethyl ellipticinium iodide (ET-2). As determined by DNA decatenati ...[more]

PMID: 26906637

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