Synthesis, crystal and molecular structure, vibrational spectroscopic, DFT and molecular docking of 4-(2-chlorobenzyl)-1-(4‑hydroxy-3- ((4-hydroxypiperidin-1-yl) methyl-5-methoxyphenyl)-[1,2,4] triazolo [4,3-a] quinazolin-5(4H)-one

Abstract

Listen

Translate article

In current work, we have firstly synthesized 4-(2-chlorobenzyl)-1-(4‑hydroxy-3- ((4-hydroxypiperidin-1-yl)methyl)-5-methoxyphenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one (1). The structural properties of 1 were explored using spectroscopy (1H NMR, 13C NMR, MS and FT-IR) and X-ray crystallography method. The single-crystal structure confirmed by X-ray diffraction was consistent with the molecular structure optimized by density functional theory (DFT) calculation at B3LYP/6–311 G (2d, p) level of theory. The geometrical parameters, molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analysis were performed by DFT using the B3LYP/6–311 G (2d, p) method. Molecular docking may suggest a favorable interaction between 1 and SHP2 protein. The molecular dynamics (MD) simulation results shown that there are hydrogen bonds, electrostatic interactions and Pi interactions between compound 1 and SHP2 proteins. The inhibitory activity of 1 on SHP2 protein at 10 μM is better than the reference compound (SHP244).