Synthesis, crystal structure, Hirshfeld surface analysis, biological evaluation, DFT calculations, and in silico ADME analysis of 4-arylidene pyrazolone derivatives as promising antibacterial agents

Abstract

The present paper describes an ultrasound-assisted synthesis of a series of 4-arylidene-1H-pyrazol-5(4H)-one derivatives (3a-i) catalyzed by sulfamic acid. The prepared compounds were characterized by physical and spectroscopic techniques and for compound 3i by single crystal X-ray diffraction analysis. Theoretical calculations such as molecular structure optimization, frontier molecular orbitals, molecular electrostatic potential, and molecular descriptors have been performed in order to get insight into the molecular structure and chemical reactivity of the synthesized compounds. The antibacterial activity of all compounds was assessed against six bacterial strains, and it was found that these compounds are good inhibitors of Gram-positive bacteria rather than Gram-negative. In addition, good oral bioavailability was predicted for all compounds by in silico calculations of ADME (absorption, distribution, metabolism, and elimination) and pharmacokinetic parameters.