PYRROLO[1,2-A]BENZIMIDAZOLE-BASED AZIRIDINYL QUINONES - A NEW CLASS OF DNA-CLEAVING AGENT EXHIBITING G-BASE AND A-BASE SPECIFICITY

被引：61

作者：

SKIBO, EB

SCHULZ, WG

机构：

[1] Department of Chemistry and Biochemistry, Arizona State University, Tempe

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 36卷 / 21期

关键词：

D O I：

10.1021/jm00073a002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pyrrolo[1,2-a]benzimiazole(PBI)-based aziridinyl quinones cleave DNA under reducing conditions specifically at G + A bases without any significant cleavage at C + T bases. The postulated mechanisms involve phosphate alkylation by the reductively activated aziridine to afford a hydrolytically labile phosphotriester as well as the classic N(7) purine alkylation followed by depurination and backbone cleavage. Evidence is presented that the phosphate alkylation mechanism could contribute. The PBIs possess a unique spectrum of cytotoxicity against cancer cells (inactive against leukemia but active against nonsmall cell lung, colon, CNS, melanoma, ovarian, and renal cancers). Also reported are results of in vivo antitumor activity screens.

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页码：3050 / 3055

页数：6

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