摘要/Abstract

设计合成了系列新的拟天然联三苯类衍生物，并对其生物活性进行了分析.其中4-氨基-（1，1'：4，1'-三联苯）-3-二醇（17）具有最强的MDA-MB-435细胞增殖抑制活性，IC₅₀为（0.20±1.12）μmol/L，显著优于我们之前报道的同类化合物X1和X2.DNA松弛实验结果表明，化合物17具有较强的DNA拓扑异构酶Ⅱα的抑制活性，但是对DNA拓扑异构酶I活性无明显抑制作用.分子模拟对接分析结果进一步验证，C环上的氮取代基对化合物17选择性抑制DNA拓扑异构酶Ⅱα活性有重要作用，为设计合成新的联三苯类高效拓扑异构酶Ⅱα抑制剂提供了新思路.
关键词: 拓扑异构酶, 联三苯, 抑制剂, 抗肿瘤
A series of natural product-like terphenyls were synthesized, and their biological activities were evaluated. 4"-Amino-[1,1':4',1"-terphenyl]-3,4-diol (17) has the most potent cytotoxic activity against the MDA-MB-435 cell line, and the IC₅₀ value is (0.20±1.12) μmol/L, which is more potent than compounds X1 and X2 obtained in our previous studies. DNA relaxation test showed that compound 17 had a strong inhibitory effect on topoisomerase Ⅱα (TOP2α), but not on topoisomerase I (TOP1), which was consistent with the docking analysis results. Our studies demonstrate that N contained substitutes on ring C are important for producing terphenyls with more efficacious activity against TOP2α, which provide insight into the development of novel terphenyl topoisomerase Ⅱα inhibitors.
Key words: topoisomerase, terphenyls, inhibitor, antitumor


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