【摘要】 对已知具有生物活性结构的基团进行对接拼合,设计合成了含双吲哚、苯并噻喃结构的3,3’-((4-氯-2H-硫色烯-3-基)亚甲基)双(1H-吲哚)类化合物.进行了目标化合物对6株肿瘤细胞的抗肿瘤实验,结果表明3,3’-((4-氯-2H-硫色烯-3-基)亚甲基)双(5-甲氧基-1H-吲哚)(5b)、3,3’-((4-氯-7-甲基-2H-硫色烯-3-基)亚甲基)双(5-甲基-1H-吲哚)(5f)和3,3’-((4-氯-7-甲基-2H-硫色烯-3-基)亚甲基)双(N-甲基-2-甲基-吲哚)(5g)对肿瘤细胞抗增殖活性较好.拓扑异构酶抑制实验结果表明,化合物5b、3,3’-((4-氯-2H-硫色烯-3-基)亚甲基)双(6-氰基-1H-吲哚)(5c)、5f和5g对DNA拓扑异构酶II有选择性抑制活性,其它化合物对DNA拓扑异构酶II表现出不同程度抑制活性.分子对接研究结果表明,化合物5b和5g与DNA拓扑异构酶II产生了较为稳定的结合,具有潜在的抗肿瘤药物研究价值.更多还原

【Abstract】 A series of 3,3’-((4-chloro-2H-thiochromen-3-yl)methylene)bis(1H-indole) analogues containing bisindole and benzothiopyran structures were designed and synthesized by docking and splicing groups with known bioactive structures.Antitumor assay against six tumor cell lines of the target compounds were screened and the results indicate that 3,3’-(4-chloro-2H-thioene-3-yl)methylene)bis(5-methoxy-1H-indole)(5b), 3,3’-(4-chloro-7-methyl-2H-thioene-3-yl)methylene)bis(5-methyl-1H-indole)(5f), and 3,3’-(4-chloro-7-methyl-2H-thioene-3-yl)methylene)bis(N-methyl-2-methylindole)(5g) showed good antiproliferative activity against tumor cells. The results of topoisomerase inhibition assay showed that compounds 5b,3,3’-(4-chloro-2H-thioene-3-yl)methylene)bis(6-cyano-1H-indole)(5c), 5f and 5g showed selective inhibitory activity against DNA topoisomerase II, while other compounds showed different levels of DNA topoisomerase II inhibition activity. The results of molecular docking studies indicated that compounds 5b and 5g had stable binding with DNA topoisomerase II, which had potential research value for antitumor drugs.更多还原