| Summary: | 碩士 === 靜宜大學 === 應用化學研究所 === 94 === This thesis is aimed at design, synthesis, and evaluation of anticancer activity of 4-arylcarbonylquinazoline derivatives as antimicrotubule agents. The indole derivatives mimic CA-4 have been demonstrated to have great inhibitory activity against tubulin polymerization. Based on the structural features, it is essential for antimicrotubule agents to possess two aryl rings by carbonyl group in cis conformation and methoxy groups on the aryl rings. Therefore, we introduced 4-benzoyl substituents on quinazoline rings which were expected to possess biological activity. The synthesis of various benzoyl group substituents at the 4-position quinazoline (7) and 6,7-dimethoxyquinazoline (8) was initiated from the cyclization of aminobenzoate and foramide. After chlorination, various benzaldehydes were used to substitute the chloride under basic condition to give the target compounds 6a-6o and 7a-7o. For 7m and 7n, the byproducts, 4-(3,4-difluorobenzyloxy)-6,7-dimethoxyquinazoline 8m and 4-(2,4-dichlorobenzyloxy)-6,7-dimethoxyquinazoline 8n were also obtained. All synthesized compounds were subjected to SRB assay to test the in vitro cytotoxicity against stomach cancer cell line AGS, lung cancer cell lines A549, liver cancer cell line HepG2, colon cancer cell line HT-29, and prostate cancer cell line PC-3. However, all compounds were not active. On the basis of computational results, it was found that these compounds were in trans form. Thus, further reduction on derivatives 7 was carried out in order to approach the cis conformation for better biological activity.
|
|---|
