新型20(S)-O-取代苯甲酸-7-苯甲酰基喜树碱酯的合成及其抗肿瘤活性

以20(S)-喜树碱为起始原料，对其进行结构修饰，在7-位导入苯甲酰基，在20-位羟基上导入取代苯甲酰基，设计并合成了11个新的20(S）-O-取代苯甲酸-7-苯甲酰基喜树碱酯化合物（4a~4k），其结构经¹H NMR， IR，MS(ESI)和元素分析表征。采用MTT法初步考察了目标化合物4a～4j对人胃癌细胞（BGC-823）、人乳腺癌细胞（MDA-MB-231）、人肺腺癌细胞（H460）及人肝癌细胞（Bel-7404）的体外抑制活性。结果表明：化合物4a、 4g和4h具有一定的体外抑瘤活性。在药物浓度为10 μmol·L^-1时，4a对MDA-MB-231细胞和H460细胞的抑制率分别为50.42%和54.40%， 4g〗对MDA-MB-231细胞的抑制率为69.91%， 4h对H460细胞抑制率为52.34%。

Synthesis and Antitumor Activities of Novel 20(S)-O-Linked Substituted Benzoic Acid-7-Benzoylcamptothecin Esters

Eleven novel 20(S)-O-linked substituted benzoic acid-7-benzoylcamptothecin esters(4a~4k) were designed and synthesized by structural modification via introduction of benzoyl on 7-position and substituted-benzoyl on 20-hydroxyl, using 20(S)-campothecin as the starting material.The structures were characterized by 1H NMR, IR, MS(ESI) and elemental analysis.The preliminary antitumor activities of 4a~4j against BGC-823, MDA-MB-231, H460 and Bel-7404 cells in vitro were investigated by MTT assay.The results showed that 4a, 4g and 4h exhibited certain antitumor activities.Inhibition rates were 50.42% against MDA-MB-231 and 54.40% against H460 for 4a, 69.91% against MDA-MB-231 for 4g and 52.34% against H460 for 4h at 10 μmol·L-1, respectively.