A New 7‐Azaindole Structure Analog: Molecular Docking, Synthesis and Preliminary Biological Activity in Vitro for Anticancer

Abstract

In this work, a series of 7-azaindole analogs were designed by the bioisosteric principle based on the pharmacodynamic parent nucleus. Moreover,pyridin-3-yl)methyl]-N-{[6-(trifluoromethyl)pyridin-3-yl]methyl}pyrimidin-2-amine (compound P1) with the strongest interaction with colony-stimulating factor 1 receptor (CSF-1R) was screened by molecular docking. Compound P1 was successfully prepared by the six-step reaction with HPLC purity of 99.26 % and characterized by 1 H-NMR and ESI-MS spectra. In vitro bioactivity study showed that compound P1 appeared the cytotoxicity to MCF-7 and A549 cells, especially to HOS cells (IC 50 = 88.79 � 8.07 nM), while it had lower toxicity to normal L929 cells (IC 50 = 140.49 � 8.03 μM). In addition, compound P1 could induce HOS cell death by apoptosis and blocking the G0/G1 phase at nanomolar concentrations. The obtained results indicated that compound P1 might be a promising candidate compound for anticancer drug.