20(S)-O-取代苯甲酸-7-乙基喜树碱酯类化合物的合成及其抗肿瘤活性

Synthesis and Antitumor Activities of 20(S)-O-linked Substituted Benzoic Acid-7-ethyl Camptothecin Ester Compounds

在AcOH/98%H2SO4体系中,喜树碱和正丙醛经烷基化反应制得7-乙基喜树碱(2);以1-乙基-3-(3-二甲基氨基丙基)碳二亚胺盐酸盐为脱水剂,4-二甲氨基吡啶为催化剂,2与取代苯甲酸直接酯化合成了一系列新型的20(S)-O-取代苯甲酸-7-乙基喜树碱酯类化合物(4a～4k),其结构经1H NMR,IR和MS表征。采用MTT法初步考察了4a～4k对人肺癌细胞(LLC-E9FP),人肺腺癌细胞(95D),人胃癌细胞(BGC-803),人胃癌细胞(HGC-27)和人肝癌细胞(7721)的抑制活性。结果表明,4b和4e对LLC-E9FP具有明显强于喜树碱的抑制活性;4h～4k对HGC-27,95D,7721也有明显的抑制活性。

7-Ethyl camptothecin（2） was obtained by alkylation of camptothecin with propaldehyde in AcOH/98%H2SO4.Eleven novel 20（S）-O-linked substituted benzoic acid-7-ethyl camptothecin ester compounds（4a^4k） were synthesized by straightforward esterification of 2 with substituted-benzoic acid using 1-3-（3-dimethylaminopropyl）-3-ethyl carbodiimide hydrochloride as the dehydrator and 4-dimethylamiopryidine as the catalyst.The structures were characterrized by 1H NMR,IR and MS.Antitumor activities of 4a^4k were investigated against five human cancer cell lines（LLC-E9FP,95D,BGC-803,HGC-27 and 7721） by MTT method in vitro.The results showed that 4b and 4e had significantly stronger antitumor activities against LLC-E9FP cell than that of camptothecin,and 4h^4k exhibited a certain antitumor activities against HGC-27,95D and 7721 cells.