Biological evaluation and in silico study of benzohydrazide derivatives as paraoxonase 1 inhibitors

Abstract

Serum paraoxonase 1 (PON1) is found in all mammalian species and is a calcium-dependent hydrolytic enzyme. PON1 hydrolyze several substrates, including carbonates, esters, and organophosphates. In the current study, we aimed to investigate the effect of the presynthesized benzohydrazide derivatives (1-9) on PON1 activity. Benzohydrazide compounds moderate inhibited PON1 with the half-maximal inhibitory concentration values ranging from 76.04 ± 13.51 to 221.70 ± 13.59 μM and K_I values ranging from 38.75 ± 12.21 to 543.50 ± 69.76 μM. Compound 4 (2-amino-4-chlorobenzohydrazide) showed the best inhibition (K_I = 38.75 ± 12.21 μM). Molecular docking and ADME-Tox studies of benzohydrazide derivatives were also carried out. In this context, we hope that the results obtained in this study contribute to the determination of the side effects of current and new benzohydrazide-based pharmacological compounds to be developed.

Keywords: ADME-Tox; benzohydrazide; in silico study; molecular docking; paraoxonase.