阿朴菲类生物碱的合成、抗黑色素瘤活性及其斑马鱼急性毒性评价  

Synthesis,anti-melanoma activity and acute toxicity of aporphine alkaloids in zebrafish

作　　者：万怡莉 仲辉 陈莉[1] 孙建博[1] WAN Yili;ZHONG Hui;CHEN Li;SUN Jianbo(School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学中药学院,南京210009

出　　处：《中国药科大学学报》2021年第5期529-535,共7页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.31870325,No.31500277)。

摘　　要：以A环1,2-亚甲二氧基为取代,合成了一系列在D环9,10,11位含不同取代基的共10个阿朴菲类生物碱,其结构均经ESI-MS、^(13)C NMR和^(1)H NMR确认。通过MTT实验探究此类化合物对B16F10黑色素瘤细胞的潜在抗肿瘤活性,并进一步分析其构效关系,同时采用斑马鱼体内急性毒性实验对活性化合物进行安全性评价。结果表明,部分化合物对肿瘤细胞具有较强的抑制活性,可以显著抑制B16F10黑色素瘤细胞的增殖,其中化合物Ⅳa的抗黑色素瘤活性最强且安全范围大,可作为抗B16F10黑色素瘤细胞增殖的先导化合物进一步研究。In this study,10 aporphine alkaloids were synthesized with 1,2-methylenedioxy substituent in ring A and 9,10,11-position with different substituents in ring D.Their structures were determined by ESI-MS,^(13)C NMR and^(1)H NMR.The potencial antitumor activity of these compounds against B16F10 melanoma cells were evaluated by MTT assay,and their structure-activity relationship was further analyzed.Meanwhile,zebrafish acute toxicity test was conducted to evaluate the safety of the active compounds.The results showed that some compounds had strong inhibitory activity on tumor cells,and could significantly inhibit the proliferation of B16F10 melanoma cells.Compound IVa has the best anti-melanoma activity with wide safety range,and can be used as a lead compound for further study on anti-proliferation of B16F10 melanoma cells.

关 键 词：阿朴菲类生物碱 合成 黑色素瘤 安全性评价 构效关系 

分 类 号：R914.5[医药卫生—药物化学] R965[医药卫生—药学]