Synthesis and cytotoxic activities of 4,5-diaryl 1,2,3-triazoles

• Main Authors: Lee Chun-Yi, 李俊誼
• Other Authors: Li, S.-Y.
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/80007371139142358250

碩士 === 中國文化大學 === 應用化學研究所 === 98 === Combretastatins, naturally occurring stilbenes, were isolated from Combretum caffrum (African Bush Willow). Among them, combretastatin A-4 (CA-4) strongly inhibited the polymerization of tubulin by binding to the colchicine site and showed most potent cytotoxicity against a variety of human cancer cell lines including multiple drug resistant cancer cell lines. CA-4 also showed strong anti-vascular activity. In the previously comparative studies of the combretastatins it appears that the cis orientation of the two aromatic rings plays an important key role of cytotoxicity. However, during storage and administration cis-combretastatin analogues tend to isomerize to trans-form. The trans-form of these compounds shows a dramatic decrease in the inhibitory effects on cancer cell growth and tublin polymerization. In order to develop new anticancer drugs, triazole ring was utilized to replace the cis double bond in CA-4. A series of 4,5-diaryl-1,2,3-triazoles were prepared and their cytotoxic activity were also evaluated against human cancer cell lines including human cervical epitheloid carcinoma (HeLa), human hepatocellular carcinoma (HepG2), and human ovarian adenocarcinoma (OVCAR-3). Among the synthesized compounds, compound 10 was the most potent compound in this series with an IC50 value 1.49 – 1.85 nM.