| Summary: | 碩士 === 靜宜大學 === 應用化學研究所 === 96 === Abstract
This thesis is aimed at design and synthesis of 1-arylpyrrolo[3,2-c]quinoline derivatives as potential anticancer agents. Combrestastatin A4 (CA-4) is a well known potent tubulin polymerization inhibitor. It is structurally similar to colchicine and competes on the position of microtubule with colchicine. The structural features of CA-4 possess two aryl rings in the cis conformation with methoxy groups on the aryl rings. Since quinoline derivatives have been found to possess biological activities in many aspects, therefore quinoline ring was chosen as skeleton for the design of 1-arylpyrrolo[3,2-c]quinoline derivatives to force the two aromatic rings in cis conformations. The synthesis was initiated from the condensation of appropriate aniline and 2-acetylbutyrolactone. After one-pot chlorination, 4-chloro-3-(2-chloroethyl)-2-methyl substituted quinoline (1) and 6,8-dimethoxyquinoline (2) were substituted by appropriate anilines. Conversion of 2,3-dihydropyrrolo[3,2-c]quinolines (4) and 6,8-dimethoxy-2,3-dihydropyrrolo[3,2-c]quinoline (5) to the fully aromatic system could conveniently be accomplished by dehydrogenation over palladium catalyst to afford target compounds 6 and 7, respectively. All synthesized compounds were subjected to SRB assay for 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. The results showed that 4-methoxy, 4-chloro and 4-bromo anilino substituted compounds 4b, 6b, 4h and 4j exhibited good inhibitory activity. Importantly, the growth inhibitory activity of 6b, dehydrogenation from 4b, was increased by 10-folds. All compounds 5 - 7 exhibit inhibitory activity. Especially, compounds 6 and 7 have higher inhibitory activity. A planar structure may be essential. Results of in vitro cytotoxicity presumed that this series of compounds have potentials as anticancer drugs.
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