Synthesis and Biological Evaluation of Novel Series Chalcone Analogues as Anti-tumor Agents

• Main Authors: Chih-Hsiang Chang, 張至翔
• Other Authors: Jin-Yi Wu
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/46538800806153619937

碩士 === 國立嘉義大學 === 生物醫藥科學研究所 === 97 === Chalcones (1, 3-diphenyl-2-propenone) are cancer preventive food components found in a human diet rich in fruits and vegetables. Besides, chalcones are known to exhibit antimitotic properties caused by inhibition of tubulin polymerization by binding to the colchicine-binding site. Its structure is similar to colchicine and combretastatin A-4 (CA-4). It has extensive cytotoxic activity in many human cancer cell lines, including prostate carcinoma, colon carcinoma, and lung carcinoma. Chalcones are well-known to exhibit antimitotic properties caused by inhibition of tubulin polymerization. In this study, we synthesized a series of chalcone analogues by modifying the A-ring and B-ring. The series of chalcone analogues are replaced C-2,3,4,5,6 of A-ring or C-3’,4’of B-ring with methoxyl, hydroxyl, halide or heterocyclic. We evaluated the cytotoxicity of these compounds in human cancer cell lines, such as bladder cancer cell line BFTC905、liver cancer cell line HepG2、colon adenocarcinoma cell line SW480、cervical epitheloid carcinoma cell line HeLa. In the present report, TM-3, TM-8, TM-9, TM-S and TM-O have potent anti-tumor activity in cultured bladder cancer cell line BFTC905 (IC50 = 0.055, 0.061, 0.15, 0.70, 1.80 μM respectively). Beside, TM-3 and TM-8 have potent anti-tumor activity in cultured colon adenocarcinoma cell line SW480 (IC50 = 0.068, 0.4 μM, respectively). Therefor, we investigated X effect that TM-3, TM-8, TM-9, TM-S and TM-O obviously increase G2/M. According to result, we study tubulin polymerization. In our study, TM-8 and TM-O have not potent suppress tubulin polymerization. In conclusion, we choose TM-3 and TM-8 have better cytotoxic activity in BFTC905 cells and new compound TM-S, which TM-3, TM-8 and TM-S may be developed as an effective new anti-tumor agent in the future.