14-Azacamptothecin: A potent water-soluble topoisomerase I poison

Kejun Cheng, Nicolas J. Rahier, Brian M. Eisenhauer, Rong Gao, S. J. Thomas, Sidney M. Hecht

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


On the basis of an analysis of luotonin A and its D-ring deaza analogue as topoisomerase I poisons and topoisomerase I-dependent cytotoxic agents, a novel analogue of the structurally related antitumor antibiotic camptothecin (CPT) was prepared. 14-Azacamptothecin was found to have much greater aqueous solubility than CPT, to inhibit topoisomerase I-mediated DNA relaxation more efficiently than CPT, and to stabilize the covalent binary complex to almost the same extent. 14-Aza CPT was found to be slightly less active than CPT in mediating cytotoxicity toward yeast expressing human topoisomerase I, possibly as a consequence of its greater off-rate from the CPT-topoisomerase I-DNA ternary complex.

Original languageEnglish (US)
Pages (from-to)838-839
Number of pages2
JournalJournal of the American Chemical Society
Issue number3
StatePublished - Jan 26 2005
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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