Antitumor Agents 155. Synthesis and Biological Evaluation of 3′,6,7-Substituted 2-Phenyl-4-quinolones as Antimicrotubule Agents

Leping Li, Hui Kang Wang, Sheng Chu Kuo, Tian-Shung Wu, Anthony Mauger, Chii M. Lin, Ernest Hamel, Kuo Hsiung Lee

Research output: Contribution to journalArticlepeer-review

138 Citations (Scopus)

Abstract

A series of 3′,6,7-substituted 2-phenyl-4-quinolones were designed and synthesized as antimitotic antitumor agents. All compounds showed cytotoxic effects (log GI 50 ≤ −4.0; log drug molar concentration required to cause 50% inhibition) against the growth of a variety of human tumor cell lines, including those derived from solid tumors such as non-small cell lung, colon, central nervous system, ovary, prostate, and breast cancers, when evaluated in the National Cancer Institute's 60 human tumor cell line in vitro screen. The most potent compound (26) demonstrated strong cytotoxic effects with GI 50 values in the nanomolar or subnanomolar range in almost all the tumor cell lines. Compound 26 was also a potent inhibitor of tubulin polymerization and radiolabeled colchicine binding to tubulin, with activity comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4.

Original languageEnglish
Pages (from-to)3400-3407
Number of pages8
JournalJournal of Medicinal Chemistry
Volume37
Issue number20
DOIs
Publication statusPublished - 1994 Sep 1

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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