姜黄素类衍生物的合成及活性研究

【作者】 陈娜；

【导师】 董金华；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2009， 硕士

【摘要】 本论文概述了姜黄素的药理作用及其在动物体内的代谢过程,重点介绍了其抗肿瘤的作用机制及其研究进展。基于构效关系分析,以提高其抗肿瘤活性,和改善代谢为目的。共合成了20个目标化合物,其中18个化合物未见文献报道。以香草醛为起始原料,经过羟基烷基化,缩合,环合反应制备了9个姜黄素吡唑类衍生物,2个姜黄素异嗯唑类衍生物。以姜黄素作为先导化合物通过羟基保护,甲基化,脱保护,Mannich反应,羟基烷基化等反应制备了8个姜黄素曼尼希碱类衍生物。在反应过程中,对实验条件进行考察,确定了一条简单、收率较高的合成路线。所合成的化合物结构经1H-NMR,MS等波谱分析确证。目前,测定了所合成的20个新目标化合物,3个反应中间体对人类慢性粒细胞白血病急变细胞系K562细胞的增殖抑制作用。初步药理结果显示,其中4个化合物显示了比姜黄素强的体外抗肿瘤活性。更多还原

【Abstract】 The pharmacological activity and the metabolism in animal of the curcumin was described in this paper. The mechanisms of anti-tumor and the research development of curcumin were briefly reviewed.Based on the analysis of the structural characteristics, the compounds were designed in order to improve its anti-tumor activity and slow the metabolic rate.20 compounds were synthesied and 18 of them were new compounds. The 9 curcumin-derived pyrazoles and 2 curcumin-derived isoxazoles were synthesized from vanillin via alkylation of the hydroxyl group, condensation reaction and ring-closing reaction.The curcumin was taken as lead compound, and 8 curcumin mannich base derivatives were designed and synthesized from curcumin via protection of the hydroxyl group, methylation, deprotection, mannich reaction and alkylation of the hydroxyl group. The synthetic methods for the intermediates were investigated and reasonable synthetic route was studied. The structures of synthesized compounds were identified by 1H-NMR spectra and MS spectra.Now the new curcumin derivatives and 3 intermediates were screened for their antitumor activity in vitro against K562 cells from human beings chronic myel-oid leukemia. Preliminary pharmacological results showed that 4 of the compounds possessed more potent antitumor activities than curcumin in vitro and IC50S were lower than curcumin.更多还原