辣椒碱类似物的合成、结构及抗肿瘤活性

Synthesis,Structures and Anti-tumor Properties of Capsaicin Analogues

以自制或试剂级羧酸、酰氯为原料,通过酰氯化、胺基化反应,设计合成了15个含香兰素胺的酰胺结构的辣椒碱类似物.其结构经IR,MS,1HNMR表征,并用X射线单晶衍射测定了化合物W5和W11的晶体结构.对所合成的化合物进行了体外抗肿瘤活性测试(MTT法),结果表明,该类化合物具有一定程度的抗肿瘤活性.化合物W1在100μg/mL时,对人宫颈癌细胞(HELA)、人肝癌细胞(SMMC-7721)、人口腔表皮癌细胞(KB)和人卵巢癌细胞(HO-8901)的抑制率均达到90%以上.当化合物W13浓度为100μg/mL时,对KB和HO-8901的抑制率分别达到89.62%和90.36%.初步构效关系分析表明,化合物中含香兰素胺的酰胺结构片段为一活性基团.

Capsaicin is a natural product existing in the fruit of capsicum,which has been used for centuries for its medical effects.Modern researches showed that capsaicin exhibits anti-proliferative activities against tumor cells.For the reason of studying the structure-activity relationship of capsaicin molecule,fifteen capsaicin analogues comprising the segment of vanillylamine acylamide were designed and synthesized from carboxy-lic acid or acyl chloride via the acylation and amidogen reactions.Their structures were characterized by IR,MS and 1H NMR techniques.The crystal structures of compounds W5 and W11 were determined by X-ray diffraction analysis.The anti-tumor properties of capsaicin analogues were evaluated against four different tumor cell lines by an MTT assay.The results suggest that the vanillylamine acylamide-containing compounds exhibited anti-proliferative activities against selected tumor cells.The inhibition rates against HELA,SMMC-7721,KB and HO-8901 of compound W1 had all reached greater than 90% at the concentration of 100 μg/mL.The inhibition rates against KB and HO-8901 of compound W13 had respectively reached 89.62% and 90.36% at the concentration of 100 μg/mL.Preliminary structure-activity relationship analysis indicates that the segment of vanillylamine acylamide is an active group in anti-tumor process.