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

万怡莉; 仲辉; 陈莉; 孙建博

doi:10.11665/j.issn.1000-5048.20210503

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

中国药科大学中药学院，南京210009

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

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出版历程
- 收稿日期: 2021-03-28
- 修回日期: 2021-09-13
- 刊出日期: 2021-10-24

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

School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China

Funds: This study was supported by the National Natural Science Foundation of China (No.31870325, No.31500277)

摘要

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、¹³C 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。
- 阿朴菲类生物碱 /
- 合成 /
- 黑色素瘤 /
- 安全性评价 /
- 构效关系
Abstract: 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,¹³C NMR and ¹H 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.
- aporphine alkaloids /
- synthesis /
- melanoma /
- safety evaluation /
- structure activity relationship

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参考文献(13)

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