[关键词]
[摘要]
目的 研究蟾皮（中华大蟾蜍Bufo bufo gargarizans的干燥皮）中的蟾蜍甾烯类成分及其细胞毒活性。方法 利用硅胶、ODS、凝胶、高效液相色谱等方法对中药蟾皮的化学成分进行分离，运用IR、UV、NMR、MS及单晶X-衍射等波谱学方法对分离得到的化合物进行结构鉴定，采用MTT法测试化合物对人肝癌HepG2细胞、人非小细胞肺癌A549细胞及人宫颈癌HeLa细胞的增殖抑制活性。结果 从蟾皮95%乙醇提取物的氯仿萃取部位共分离鉴定了14个蟾蜍甾烯类成分，分别为3，23-二羟基-γ-内酯-24-去甲-14，20（22）-二烯-21-胆酸（1）、3-表-酯蟾毒配基（2）、3-表-去乙酰华蟾蜍精（3）、3-表-蟾蜍灵（4）、3-氧-去乙酰华蟾蜍精（5）、3-氧-蟾蜍它灵（6）、3-氧-伪沙蟾蜍精（7）、3-oxo-Δ4（5）-resibufogenin（8）、3-oxo-Δ4（5）-cinobufotalin（9）、3-dehydroscillarenin（10）、3-氧-毛地黄毒苷配基（11）、digirezigenin（12）、bufogargarizin A（13）、bufogargarizin B（14）。化合物6、9、10对HepG2、A549及HeLa细胞具有显著的增殖抑制活性，半数抑制浓度（IC50）为0.11~1.67 μmol/L。结论 化合物1为新天然产物，并首次报道其核磁数据；化合物1~14均为首次从蟾皮中分离得到；化合物6、9、10具有显著的细胞毒活性。
[Key word]
[Abstract]
Objective To investigate the cytotoxic bufadienolides from the skin of Bufo bufo gargarizans. Methods Compounds were isolated by a combination of various chromatographic methods including silica gel, ODS and HPLC, and their structures were elucidated based on spectroscopic analyses (IR, UV, NMR, and MS) and single crystal X-ray diffraction. The in vitro cytotoxic activities of 10 bufadienolides were evaluated in HepG2, A549, and Hela cells by MTT assay. Results A total of 14 compounds were isolated from the skin of B. bufo gargarizans and identified as 3,23-dihydroxy-γ-lactone-24-norchola-14,20(22)-dien-21-oicacid (1), 3-epi-resibufogenin (2), 3-epi-desacetylcinobufagin (3), 3-epi-bufalin (4), 3-ketodesacetylcinobufagin (5), 3-oxo-cinobufagin (6), 3-oxo-ψ-bufarenogin (7), 3-oxo-Δ4(5)-resibufogenin (8), 3-oxo-Δ4(5)-cinobufotalin (9), 3-dehydroscillarenin (10), 3-dehydrodigitoxigenin (11), digirezigenin (12), bufogargarizin A (13), and bufogargarizin B (14). Three compounds (6, 9, and 10) displayed significant anti-proliferative activities on HepG2, A549 and Hela cells with IC50 values of 0.11-1.67 μmol/L. Conclusion Compound 1 is a new natural product. Compounds 1-14 are reported for the first time in the skin of B. bufo gargarizans. Compounds 6, 9, and 10 show significant cytotoxic activities.
[中图分类号]
R284.1
[基金项目]
国家自然科学基金项目（81860760）；云南省应用基础研究计划项目（2017FD110）；云南民族大学民族药资源化学国家民族事务委员会-教育部重点实验室开放基金（MZY1608）
