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

作者：Reddy M Vijaya Bhaskar; Shen Yuh Chiang; Yang Jai Sing; Hwang Tsong Long; Bastow Kenneth F; Qian Keduo; Lee Kuo Hsiung^*; Wu Tian Shung

来源：Bioorganic & Medicinal Chemistry, 2011, 19(6): 1895-1906.

DOI：10.1016/j.bmc.2011.02.004

• Bichalcone analogs
• Nitric oxide production inhibition
• Cytotoxicity
• Apoptosis

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 mu M, 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-kappa B p65 and up-regulation of iNOS at 1.0 mu M. Compound 4 and three other analogs (3, 20, and 23) exerted significant in vitro anticancer activity GI(50) values ranging from 0.70 to 13.10 mu M. A mode of action study using HT-29 colon cancer cells showed that 23 acts by inducing apoptosis signaling.

• 出版日期2011-3-15
• 单位长春大学; 中国医科大学