Zidar Nace, Secci Daniela, Tomašič Tihomir, Mašič Lucija Peterlin, Kikelj Danijel, Passarella Daniele, Argaez Aida Nelly Garcia, Hyeraci Mariafrancesca, Dalla Via Lisa
University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.
Department of Chemistry, University of Milan, Via Golgi 19, 20133 Milan, Italy.
ACS Med Chem Lett. 2020 Jan 24;11(5):691-697. doi: 10.1021/acsmedchemlett.9b00557. eCollection 2020 May 14.
A series of 3-methyl-2-phenyl-1-indoles was prepared and investigated for antiproliferative activity on three human tumor cell lines, HeLa, A2780, and MSTO-211H, and some structure-activity relationships were drawn up. The GI values of the most potent compounds ( and ) were lower than 5 μM in all tested cell lines. For the most biologically relevant derivatives, the effect on human DNA topoisomerase II relaxation activity was investigated, which highlighted the good correlation between the antiproliferative effect and topoisomerase II inhibition. The most potent derivative, , was shown to induce the apoptosis pathway. The obtained results highlight 3-methyl-2-phenyl-1-indole as a promising scaffold for further optimization of compounds with potent antiproliferative and antitopoisomerase II activities.
制备了一系列3-甲基-2-苯基-1-吲哚，并研究了它们对三种人类肿瘤细胞系HeLa、A2780和MSTO-211H的抗增殖活性，得出了一些构效关系。在所有测试细胞系中，最具活性的化合物（和）的GI值均低于5μM。对于最具生物学相关性的衍生物，研究了其对人DNA拓扑异构酶II松弛活性的影响，这突出了抗增殖作用与拓扑异构酶II抑制之间的良好相关性。最具活性的衍生物被证明可诱导凋亡途径。所得结果表明，3-甲基-2-苯基-1-吲哚是进一步优化具有强效抗增殖和抗拓扑异构酶II活性化合物的有前景的骨架。
