南海海绵Pseudoceratina sp.化学成分的细胞毒协同增效作用及靶点预测  

Cytotoxic Synergism and Target Prediction of Chemical Constituents from the South China Sea Sponge Pseudoceratina sp.

作　　者：竺婷婷 袁慧慧 胡瑾怡 蓝闽波 ZHU Tingting;YUAN Huihui;HU Jinyi;LAN Minbo(Shanghai Key Laboratory of Function Materials Chemistry,School of Chemistry and Molecular Engineering,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学化学与分子工程学院,上海市功能性材料化学重点实验室,上海200237

出　　处：《华东理工大学学报（自然科学版）》2021年第5期577-583,共7页Journal of East China University of Science and Technology

基　　金：国家自然科学基金面上项目(41576157)。

摘　　要：以肿瘤细胞毒活性筛选为导向,采用硅胶柱色谱及高效液相色谱等现代色谱技术对南海海绵Pseudoceratina sp.化学成分进行分离纯化,并利用电喷雾质谱和核磁共振波谱等波谱技术对化合物进行结构表征;采用磺酰罗丹明B(SRB)法评价化学成分对人肺癌细胞A549、人肝癌细胞HepG2和人宫颈癌细胞HeLa的增殖抑制作用,分析化学成分和单一化合物的细胞毒活性,探讨可能的联合作用机制;采用Chemmapper Server对化合物进行靶点计算,推测作用靶点。结果表明,从南海海绵Pseudoceratina sp.中分离并鉴定得到溴代酪氨酸类生物碱hemifistularin-3(1)和11,19-dideoxyfistularin 3(2),2个化合物对3种肿瘤细胞的半数抑制浓度(IC_(50))均大于91.76μmol/L,而以一定配比时IC_(50)可达到8.71μmol/L,二者对肿瘤细胞的增殖抑制具有明显的协同作用;2个化合物作用靶点可能集中在热休克转录因子1和辣椒素受体1,而协同作用可能跟化合物的多靶标作用相关。Based on the screening of tumor cytotoxicity,fractions and compounds from the South China Sea sponge Pseudoceratina sp.were isolated and purified by silica gel column and HPLC.The structures were identified by ESI-MS and NMR spectroscopy.The anti-proliferation of fractions and compounds against A549,HepG2 and HeLa cell lines had been investigated by SRB method.The targets in the cell were calculated and predicted by Chemmapper Server.The results showed that two bromotyrosine alkaloids were obtained and identified as hemifistularin-3(1)and 11,19-dideoxyfistularin 3(2).Their IC_(50) values were higher than 91.76μmol/L against three tumor cells.While the combination of the two compounds at a certain ratio showed good cytotoxicity,the IC_(50) value against A549 cells was as low as 8.71μmol/L,which indicated that the two compounds had significant synergistic effect on three tested tumor cells.Their targets might focus on Hsf1 protein and Vanilloid Receptor 1 and the synergistic effect might be associated with multi-target of compounds.

关 键 词：海绵Pseudoceratina sp. 细胞毒 分离纯化 协同作用 靶点预测 

分 类 号：R285[医药卫生—中药学]