Antitumor agents. 280. Multidrug resistance-selective desmosdumotin B analogues

Kyoko Nakagawa-Goto, Po Cheng Chang, Chin Yu Lai, Hsin Yi Hung, Tzu Hsuan Chen, Pei Chi Wu, Hao Zhu, Alexander Sedykh, Kenneth F. Bastow, Kuo Hsiung Lee

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring modifications on MDR-selectivity. Analogues with a B-ring Me (3) or Et (4) group had substantially increased MDR selectivity. Three new disubstituted analogues, 35, 37, and 49, also had high collateral sensitivity (CS) indices of 273, 250, and 100, respectively. Furthermore, 2-4 also displayed MDR selectivity in an MDR hepatoma-cell system. While 2-4 showed either no or very weak inhibition of cellular P-glycoprotein (P-gp) activity, they either activated or inhibited the actions of the first generation P-gp inhibitors verapamil or cyclosporin, respectively.

Original languageEnglish
Pages (from-to)6699-6705
Number of pages7
JournalJournal of Medicinal Chemistry
Volume53
Issue number18
DOIs
Publication statusPublished - 2010 Sep 23

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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