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Several anti-tumor cell lines and carbonic anhydrase Ⅱ model were established. More than 10000 compounds and extracts from plants were screened using these models and about 10 compounds showed strong inhibitory activities. Two species of plants Inula helianthus-aquatica and Saussurea deltoidea were chosen to investigate chemical and bioactivity constituents based on the results of screening of extracts and fractions. 58 compounds were isolated and identified from these two plants, 6 compounds were found to be new and 14 compounds showed anti-tumor activities. We also studied the anti-tumor mechanism of the compound bigelovin isolated from Inula helianthus-aquatica. Bigelovin was found with apoptotic activity against cell line U266 by lowering the amount of important transcription factor E2F-1 which inhibits the cell cycle at G0/G1 stage. Docking study on 7 natural new phenolic inhibitors of CA Ⅱ and 3D-QSAR study on 61 sulfonamide inhibitors of CA Ⅱwere also investigated. The calculated results were in good correlation with experimental results.

基于以上两种重要疾病和研究组方向,本论文工作开展了多个肿瘤细胞株和碳酸酐酶Ⅱ靶标模型的建立和筛选工作,累计筛选1万多个/次样品,发现10余个活性较强化合物;从粗提取物筛选结果中选取两种抗肿瘤活性强的菊科植物水朝阳旋覆花(Inula helianthus-aquatica)和三角叶凤毛菊进行了系统化学和活性成分研究,分离鉴定了58个化合物,发现6个新化合物和14个抗肿瘤活性化合物;通过合作对水朝阳旋覆花中活性较强的bigelovin进行了抗肿瘤作用机制研究,发现它可能是通过降低G2期重要的转录因子E2F-1,致使细胞周期阻滞在G0/G1期,引起多发性骨髓瘤U266细胞凋亡;开展了7个新的天然酚类CAⅡ抑制剂的对接研究和61个合成的系列磺酰胺类CAⅡ抑制剂的3D-QSAR分析,结果表明计算与实验一致。

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