Substituted 2,5'-Bi-1H-benzimidazoles: topoisomerase I inhibition and cytotoxicity

J Med Chem. 1996 Feb 16;39(4):992-8. doi: 10.1021/jm950412w.

Abstract

Several 2'-aryl-5-substituted-2,5'bi-1H-benzimidazole derivatives were synthesized and evaluated as topoisomerase I poisons and for their cytotoxicity toward the human lymphoblast cell line RPMI 8402. This study focused on 18 2,5'-bi-1H-benzimidazole derivatives which contained either a 5-cyano, a 5-(aminocarbonyl), or a 5-(4-methylpiperazinyl) group. Among these bibenzimidazoles, the pharmacological activity of 2'-phenyl derivatives and the influence of the different positional isomers of either a 2'-tolyl group or a 2'-naphthyl moiety on cytotoxicity and topoisomerase I inhibitory activity were determined.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / toxicity
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / pharmacology*
  • Benzimidazoles / toxicity
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / toxicity
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Enzyme Inhibitors
  • Topoisomerase I Inhibitors
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