Design, Synthesis and Anticancer Activity Studies of Novel Indole-Pyrimidine Biaryl Derivatives

A series of novel indole-pyrimidine biaryl derivatives were designed, synthesized and evaluated for inhibitory activity against Lysine Specific Demethylase 1 (LSD1) and antiproliferative activity against five selected cancer cell lines (MGC-803, PC-3, EC-109, PC-12 and MCF-7). The priliminary structure-activity relationship (SAR) for this indole-pyrimidine biaryl scaffold was explored with evaluation of 22 variants of the structural class. Among these analogues, compound 1-(4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)piperazin-1-yl)-2-((3,4,5-trimethoxyphenyl)amino)ethan-1-one (6i) exhibited the potential inhibitory activity against LSD1 (IC50=1.03 mu mol/L), compounds 1-(4-(4-(1-methyl-1H-indol3-yl)pyrimidin-2-yl)piperazin-1-yl)-2-(m-tolylamino)ethan-1-one (6c), 2-((4-butylphenyl)amino)-1-(4-(4-(1-methyl-1H-indol3-yl)pyrimidin-2-yl)piperazin-1-yl)ethan-1-one (6f) and 2-((3-fluorophenyl)amino)-1-(4-(4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)piperazin-1-yl)ethan-1-one (6k) showed the potential inhibitory activity aginst PC-3 cells. Especially, compound 6k exhibited the best antitumor activity (IC50=2.75 mu mol/L), which was served as bioactive fragment and hit compound for developing more potent antitumor agents.

Automated summary

Novel indole-pyrimidine biaryl derivatives were designed, synthesized, and evaluated for inhibitory activity against LSD1 and antiproliferative activity against selected cancer cell lines. Compound 6i showed potential inhibitory activity against LSD1, while compounds 6c, 6f, and 6k exhibited potential inhibitory activity against PC-3 cells, with compound 6k showing the best antitumor activity.