Synthesis and spectroscopic study of two new pyrazole derivatives with detailed computational evaluation of their reactivity and pharmaceutical potential

Abstract

© 2019 Elsevier B.V. The synthesis of two pyrazole derivatives, 4-[2-(3-Chloro-2-methylphenyl)hydrazinylidene]-5-methyl-2,4-dihydro-3H-pyrazol-3-one (CPMHP-I)and 4-[2-(3-Chloro-4-fluorophenyl) hydrazinylidene]-5-methyl-2,4-dihydro-3H-pyrazol-3-one (CFHMP-II) and characterization by NMR, FT-Raman, FT-IR and elemental analysis are reported in this work. In this work several computational techniques are used to obtain information about reactive properties of two pyrazole derivatives, CPMHP-I and CFHMP-II. Computational approaches encompassed density functional theory (DFT) calculations, molecular dynamics (MD) simulations and molecular docking. While DFT calculations enabled us to get different reactive properties of title molecules, MD simulations gave us an insight into the stability in water and indicated the possible choices for excipients. The downshift of NH stretching in the IR from the calculated wavenumber is due to hydrogen bonding supported by NBO analysis. The NH stretching modes in the VCD spectra are excellent markers. The docking output propose that CPMHP-I might shows inhibitory activity against human microsomal prostaglandin E synthase 1 and CFHMP-II might exhibit inhibitory activity against mycobacterium tuberculosis type II and can be developed as a new anti-TB drug.