NO供体型苦参碱衍生物的合成及抗肿瘤活性

Synthesis and Anti-cancer Activity of Nitric Oxide Donor-based Matrine Derivatives

以苦参碱为原料,设计合成了13个NO供体型苦参碱衍生物,衍生物的结构经EI-MS,1HNMR,IR和元素分析确证.采用MTT法测试所合成化合物的体外抗肿瘤活性,结果表明,所合成的化合物均有一定的抗肿瘤作用,其中化合物11a～11c,11h,11i对肝癌细胞HepG2的抑制活性优于5-氟尿嘧啶.

Matrine,one of the major active alkaloids isolated from the Sophora alopecuroides L which is a useful Chinese herbal drug,possesses antipyretic,anti-inflammatory,analgesic,and notable antiviral activities,and has been used for the treatment of lipopolysaccharide-induced liver injury.Recently,it was reported that matrine could inhibit the growth of tumor cells.Nitric oxide（NO）,a free radical molecule,is involved in numerous physiological and pathological processes.High levels of NO usually are toxic to tumor cells.It was therefore of interest to determine whether the hybrid of matrine and NO donor furoxan would provide a hitherto unknown class of matrine derivatives that possess potent anticancer activity.Herein furoxan-based matrine compounds 11a—11m were designed and synthesized,and their structures were confirmed by MS,IR,^1H NMR spectra and elemental analysis.All target compounds exhibited expectedly much more stronger anti human hepatocellular carcinoma cells（HepG2 cells） activity than that of parent compound matrine in vivo.Furthermore,compounds 11a—11c,11h and 11i had stronger cytotoxic activities than that of control 5-fluorouracil.The concept of designing NO donor-based matrine derivatives that possess potent anticancer activity warrants further investigation.