Bis-chalcone analogues as potent NO production inhibitors and as cytotoxic agents

M. Vijaya Bhaskar Reddy, Yuh Chiang Shen, Emika Ohkoshi, Kenneth F. Bastow, Keduo Qian, Kuo Hsiung Lee, Tian Shung Wu

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Chalcones have a distinctive 1,3-diarylpropenone skeleton and exert numerous biological effects. Using a one-step Claisen-Schmidt condensation, we synthesized eleven bis-chalcones (3-13) and three acetyl chalcones (14-16) from substituted aldehydes and diacetylresorcinol. The compounds were tested for in vitro cytotoxic activity against four human cancer cell lines (A549, DU145, KB, and KB-VIN) and inhibition of NO production in lipopolysaccharide (LPS)-activated microglial cells. Among them, four compounds (3, 5, 6, and 13) showed significant cytotoxic activity with EC 50 values ranging from 1.57 to 5.14 μM, and seven compounds (3, 5-8, 10, and 13) displayed potent anti-inflammatory activity by inhibiting NO production with IC 50 values ranging from 0.95 to 8.65 μM. A mechanism of action study of active compounds 6 and 7 discovered that these compounds down-regulated iNOS expression by inhibiting p65 NF-κB activation/nuclear translocation due to prevention of IκBα degradation. Structure-activity relationship (SAR) findings are also discussed.

Original languageEnglish
Pages (from-to)97-103
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume47
Issue number1
DOIs
Publication statusPublished - 2012 Jan

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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