Designs and Biological Studies of Ursolic Acid, Chalcone, and Anthraquinone Derivatives as Targeted Anticancer Agents

• Main Authors: Huang-Yao Tu, 涂皇堯
• Other Authors: Shyh-Chyun Yang
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/98036184556660519251

博士 === 高雄醫學大學 === 藥學研究所 === 98 === Ursolic acid derivatives (2-24), chalcone derivatives (27-43 and 45), and anthraquinone derivatives (50-62) were synthesized, evaluated for cytotoxicities against cancer cell lines, and discussed their biological activities in this study. All these synthesized derivatives exhibited cytotoxicities against several cancer cell lines and were elucidated their structures and cytotoxic activity relationships. Among synthesized chalcone derivatives, compounds 37 and 41 with a 4-carbamoyl moiety showed potent cytotoxic activities against human bladder and prostate cancer cell lines. Results indicated that these chalcone derivatives interfered microtubule dynamics, led to cell cycle arrest, and further induced apoptosis. Among ursolic acid deriviatives, compounds 5 and 17 with an isopropyl moiety at C-17-COOH and a succinyl moiety at C-3-OH showed the potent inhibitory effect on the growth of the human bladder cancer cell line. Among synthesized anthraquinone derivatives, compound 54 possessed of a pyrrolidinyl group induced stronger cytotoxic effect. Ursolic acid and anthraquinone derivatives were further studied for their mediation of the generation of reactive oxygen species (ROS) in human cancer cells and found the induction of generation of ROS, cell cycle arrest, and apoptosis. These biological assays indicated that ursolic acid and anthraquinone derivatives might influence microtubules or molecules in cancer cells and led to abnormal growth and death. It suggested that these three kinds of synthesized derivatives might be used as targeted anticancer agents.