New bichalcone analogs as NF-κB inhibitors and as cytotoxic agents inducing Fas/CD95-dependent apoptosis

M. Vijaya Bhaskar Reddy, Yuh Chiang Shen, Jai Sing Yang, Tsong Long Hwang, Kenneth F. Bastow, Keduo Qian, Kuo Hsiung Lee, Tian Shung Wu

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24 Citations (Scopus)

Abstract

A series of novel bichalcone analogs were synthesized and evaluated in lipopolysaccharide (LPS)-activated microglial cells as inhibitors of nitric oxide (NO) and for in vitro anticancer activity using a limited panel of four human cancer cell lines. All analogs inhibited NO production. Compounds 4 and 11 exhibited optimal activity with IC50 values of 0.3 and 0.5 μM, respectively, and were at least 38-fold better than the positive control. A mechanism of action study showed that both compounds significantly blocked the nuclear translocation of NF-κB p65 and up-regulation of iNOS at 1.0 μM. Compound 4 and three other analogs (3, 20, and 23) exerted significant in vitro anticancer activity GI50 values ranging from 0.70 to 13.10 μM. A mode of action study using HT-29 colon cancer cells showed that 23 acts by inducing apoptosis signaling.

Original languageEnglish
Pages (from-to)1895-1906
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number6
DOIs
Publication statusPublished - 2011 Mar 15

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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    Reddy, M. V. B., Shen, Y. C., Yang, J. S., Hwang, T. L., Bastow, K. F., Qian, K., Lee, K. H., & Wu, T. S. (2011). New bichalcone analogs as NF-κB inhibitors and as cytotoxic agents inducing Fas/CD95-dependent apoptosis. Bioorganic and Medicinal Chemistry, 19(6), 1895-1906. https://doi.org/10.1016/j.bmc.2011.02.004