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

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

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10μmol·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%。

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 of4a ~4j against BGC-823, MDA-MB-231, H460 and Bel-7404 cells in vitro were investigated by MTY 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% a- gainst MDA-MB-231 for 4g and 52.34% against H460 for 4h at 10 μmol·L^-1 , respectively.