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Review Article

The Discovery of the Pyrrolo[1,2-a]benzimidazole Antitumor Agents - The Design of Selective Antitumor Agents

[ Vol. 3 , Issue. 1 ]

Author(s):

E. B. Skibo   Pages 47 - 78 ( 32 )

Abstract:


This review presents the design, chemistry, cytotoxicity, and antitumor activity of agents based on the pyrrolo[1,2-a]benzimidazole ring system. The 6-aziridinyl derivatives (PBIs) alkylate and cleave DNA upon two electron reduction as a result of phosphate nucleophile-mediated opening of the protonated aziridine ring. The 6-acetamido quinone (ABSI) and iminoquinone (imino-ABSI) derivatives do not require reductive activation to exert cytotoxicity. The 6-acetamido quinone derivatives act as DNA intercalating agents and inhibit the first step of topoisomerase II mediated DNA relaxation. The PBIs were found to exhibit high toxicity in mice with minimal antitumor activity. In contrast, the ABSIs showed significant increases in life spans of mice as well as activity against tumors distant from the injection site.

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