Synthesis, Antiproliferative Effect, and Topoisomerase II Inhibitory Activity of 3-Methyl-2-phenyl-1H-indoles

被引：21

作者：

Zidar, Nace ^{[2
]}

Secci, Daniela ^{[2
]}

Tomasic, Tihomir ^{[2
]}

Masic, Lucija Peterlin ^{[2
]}

Kikelj, Danijel ^{[2
]}

Passarella, Daniele ^{[3
]}

Argaez, Aida Nelly Garcia ^{[4
]}

Hyeraci, Mariafrancesca ^{[4
]}

Dalla Via, Lisa ^{[1
]}

机构：

[1] Univ Padua, Dept Pharmaceut & Pharmacol Sci, I-35131 Padua, Italy

[2] Univ Ljubljana, Fac Pharm, Ljubljana 1000, Slovenia

[3] Univ Milan, Dept Chem, I-20133 Milan, Italy

[4] Univ Padua, Dept Pharmaceut & Pharmacol Sci, I-135131 Padua, Italy

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2020年 / 11卷 / 05期

关键词：

3-Methyl-2-phenyl-1H-indole; antiproliferative activity; topoisomerase II; apoptosis; CATALYTIC INHIBITORS; REPLICATION; FLAVONOIDS; DISCOVERY; LUTEOLIN; POISONS;

D O I：

10.1021/acsmedchemlett.9b00557

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 3-methyl-2-phenyl-1H-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(50) values of the most potent compounds (32 and 33) were lower than 5 mu M 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, 32, was shown to induce the apoptosis pathway. The obtained results highlight 3-methyl-2-phenyl-1H-indole as a promising scaffold for further optimization of compounds with potent antiproliferative and antitopoisomerase II activities.

引用

页码：691 / 697

页数：7

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