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

Korkmaz I. N., TÜRKEŞ C., Demir Y., ÖZTEKİN A., ÖZDEMİR H., BEYDEMİR Ş.

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, vol.36, no.11, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 36 Issue: 11
  • Publication Date: 2022
  • Doi Number: 10.1002/jbt.23180
  • Journal Name: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE
  • Keywords: ADME-Tox, benzohydrazide, in silico study, molecular docking, paraoxonase, CALCIUM-CHANNEL BLOCKERS, CARBONIC-ANHYDRASE, PYRAZOLE DERIVATIVES, ACCURATE DOCKING, VITRO, GLIDE, ACETYLCHOLINESTERASE, PREDICTION
  • Anadolu University Affiliated: Yes

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 mu M and K-I values ranging from 38.75 +/- 12.21 to 543.50 +/- 69.76 mu M. Compound 4 (2-amino-4-chlorobenzohydrazide) showed the best inhibition (K-I = 38.75 +/- 12.21 mu M). 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.