Synthesis, crystal structure, DFT, molecular docking and antitumor activity of 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-((4-methylpiperidin-1-yl)methyl)phenyl)-[1,2,4] triazolo[4,3-a]quinazolin-5(4H)-one

In this study, the compound 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-((4-methylpiperidin-1-yl)methyl)phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one (1) was synthesized for the first time, and its structure was characterized by H-1 NMR, C-13 NMR, MS and FT-IR spectra. Single crystals of compound 1 were grown in acetonitrile and the structure was confirmed by X-ray diffraction. The DFT-optimized structure was consistent with that determined by X-ray diffraction. Geometrical parameter, molecular electrostatic potential and frontier molecular orbital analyses were performed using the DFT/B3LYP/6-311G (2d, p) method. The vibrational assignment was based on the characteristic vibrational absorption band of compound 1. The theoretical and experimental C-13 NMR chemical shifts exhibited good correlation. Molecular docking suggests favorable interactions between compound 1 and SHP2 protein. The SHP2 enzyme inhibition rate of compound 1 was 12.40% at 10 mu M. The antitumor activity of 1 was better than that of the reference compound in human hepatoma cells SMMC7721 (IC50 =757 mu M) and human melanoma cells A375 (IC50 =70.19 mu M). [GRAPHICS] .

Automated summary

In this study, a novel compound was synthesized and characterized using various spectroscopic methods. Molecular docking analysis indicated potential interactions between the compound and SHP2 protein. In vitro experiments demonstrated promising antitumor activity of the compound.