Benzenesulfonohydrazides inhibiting urease: Design, synthesis, their in vitro and in silico studies

Keeping in view the therapeutic importance of ureases due to its involvement in different pathological conditions, its inhibition was investigated by newly synthesized benzenesulfonohydrazides. Elemental analysis, IR, H-1 NMR and C-13 NMR spectral studies were performed to elucidate the structure of benzenesulfonohydrazides. In vitro urease enzyme inhibition assay revealed the compound INS-5 was found to be the most potent (IC50 = 1.11 +/- 0.29 mu M) among the tested compounds. The compound INS-2 was competitive inhibitor with Ki value 5.60 mu M while the compounds INS-1 and INS-5 were mixed type of inhibitors with Ki values 4.32 and 2.76 mu M respectively. Ancillary to synthetic studies, DFT and TDDFT calculations at B3LYP/6-311G(d,p) level of theory were performed for comparative analysis of spectroscopic data, frontier molecular orbitals (FMOs), natural bond orbital (NBO) analysis and molecule electrostatic potential (MEP) surface. Overall, experimental findings were supported nicely by corresponding DFT computed results. The NBO analysis confirmed that the presence of hyperconjugative interactions are pivotal cause for stability of investigated compounds. Global reactivity descriptors were also calculated using the energies of FMOs energies. Molecular docking studies were performed to identify the plausible binding mode of the competitive inhibitor. (C) 2020 Published by Elsevier B.V.