黄芩素氨基酸衍生物的合成及体外细胞毒活性评价

Synthesis and in vitro cytotoxicity evaluation of baicalein amino acid derivatives

摘要: 目的:合成天然产物黄芩素的氨基酸衍生物并进行体外抗肿瘤活性评价。方法:氨基酸经酯化和酰化,在吡啶溶液中通过甲醛与黄芩素反应,制得黄芩素8位引入氨基酸侧链的衍生物;氨基酸经羧基保护和氨基酰化、黄芩素经羟基保护,制得黄芩素6位引入氨基酸侧链的衍生物。衍生物结构经质谱(MS)、核磁共振光谱(NMR)和红外光谱(IR)确证。结果:设计合成了未见文献报道的13个新的黄芩素衍生物,采用MTT法评价了目标化合物对人肝癌细胞HepG2生长的抑制活性。结论:化合物4c,4d,7a和7b显示较黄芩素高的体外抗肿瘤活性。

Abstract: AIM:To synthesize the baicalein amino acid derivatives and evaluate their cytotoxicity activities in vitro.METHODS:Amino acids were subjected to methylation and aminoacylation reaction,then reacted with formaldehyde and baicalein to synthesize baicalein-8 benzyl amino acid derivatives.Through carboxyl group protection and aminoacylation of amino acid and benzyl protection of baicalein,derivatives of baicalein-6-O-amino acid esters were obtained.All of the target compounds were identified by IR,MS and 1H NMR.RESULTS:Thirteen novel derivatives were synthesized and characterized.Their cytotoxic activities were assessed by the MTT method on the inhibition of HepG2 cells in vitro.CONCLUSION:Compounds 4c,4d,7a and 7b showed a significant increase in cytotoxicity compared with baicalein.