Crystal structure, Hirshfeld surface and DFT computations, along with molecular docking investigations of a new pyrazole as a tyrosine kinase inhibitor

Abstract

In the present work we report the experimental and computational investigations of (2-aminophenyl)[4-(4-chlorophenyl)-1,3-diphenyl-1H-pyrazol-5-yl]methanone (C28H20ClN3O). X-ray diffraction (XRD) showed that the undertaken compound 3 crystallized in a monoclinic system, space group P21/n. The structure exhibited both inter- and intramolecular hydrogen bonding contacts of the type N—H···X (X= O, N, Cl) and C—H···O, which ensured the stabilization of the crystal then the molecular structure. Hirshfeld surface analysis (HSA) showed that other unconventional interactions such as H⋯H (48%) and C⋯H (28%) contributed as well in the molecular assembly. The energy of the HOMO and LUMO orbitals, the molecular electrostatic potential (MEP) and the absorption spectrum were generated using the density functional theory (DFT). The MEP map showed areas of the negative potential region around the electronegative atoms O1 and N3, while the maximum positive sites were around the hydrogen atoms of the amine group. The experimental and computed UV-Vis spectra showed the presence of π-π* and n-π* transitions. The computational results showed that the geometrical and electronic parameters were consistent and in accordance with the experimental data. The anticancer activity of the studied pyrazole was investigated in-silico via molecular docking (MD) towards EGFR tyrosine kinases (PDB ID: 1M17 and 2ITN). The outcomes suggest that the pyrazole 3 has significant interaction with the target receptors. Afterwards, drug properties were investigated by ADME/T analysis, which show that the examined pyrazole 3 has an excellent pharmacokinetic profile and no toxicity risks.