7-对氟苯甲酰基喜树碱的合成及其抗癌活性研究

Synthesis and Antitumor Activity of 7-(p-Fluorobenzoyl)camptothecin

为提高天然喜树碱的活性并降低其毒性,在它的7位引进了含氟的亲脂基团。以对氟苯甲醛、20(S)-喜树碱等为原料,经Fenton自由基取代反应,合成了7-对氟苯甲酰基-20(S)-喜树碱,产率38.5%,合成的新化合物结构经MS、1HNMR和IR确证,并对FeSO4.7H2O?过氧化氢?对氟苯甲醛?浓硫酸的投料量等反应条件进行了初步优化。目标产物经北京大学药学院天然药物及仿生药物国家重点实验室用磺酰罗丹明B(SRB)法在体外对人癌细胞增殖的抑制作用进行了测定,结果表明,在20μmol/L时,该化合物对人白血病(HL-60)、人胃癌(BGC-823)、人肝癌(Bel-7402)3种人癌细胞增殖都有抑制作用。

In order to enhance the activity of natural camptothecin and reduce its toxlcity,the lipophilic group including fluorine was introduced into the 7th position of natural camptothecin. 7-（ pFluorobenzoyl） camptothecin was synthesized from p-fluorobenzaldehyde and 20 （S） -camptothecin by Fenton radical substitution reaction in 38.5% yield. Structure of the new compound was confirmed by IR, 1^HNMR, MS and elementary analysis. The reaction conditions were optimized. The antitumor activity of the target compound was tested in vitro by Sulforhodamine B （SRB） assay. The preliminary bioassay indicated that the compound has antitumor activity against HL- 60, BGC -823 and Bel- 7402.