Synthesis of cis-Stilbene Analogues with Antitumor Activity

• Main Authors: Tien,Ya-Lun, 田雅倫
• Other Authors: Tsai,Chii-Tang
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/74604133479350109221

碩士 === 中國文化大學 === 應用化學研究所 === 97 === A series of compounds (combretastatins) were isolated from the bark of the South African tree Combretum caffrum. They inhibited the polymerization of tubulin and exhibited antimitotic acticity. Among them, combretastatin A-4 (CA-4) with a cis structure showed the most potent cytotoxicity against a variety of human cancer cell lines including multiple drug resistant cancer cell lines. However, during storage and administration, CA-4 tended to isomerize to its trans isomer, which showed a dramatic decrease in the inhibitory effects on cancer cell growth and tubulin polymerization. Therefore, more stable analogues of combretastatin A-4 were synthesized and their activties were investigated. In this study, we synthesized a series of compounds, in which the double bond between two benzene rings was trisubstituted and could be more stable than CA-4. These compounds were synthesized by a renction of a benzaldehyde and an isochroman-3-one and three (E)-4-benzylidene isochroman-3-ones (7, 10, 11) and three (E)-4-(naphthalen-2-ylmethylene)isochroman-3-ones (12, 14, 17) were obtained.