Methyl benzoate derivatives: in vitro Paraoxonase 1 inhibition and in silico studies

Paraoxonase 1 (PON1) can metabolize some compounds such as aromatic carboxylic acid and unsaturated aliphatic esters, arylesters, cyclic carbonate, plucuronide drugs, some carbamate insecticide classes, nerve gases, and lactone compounds. Methyl benzoate has recently been shown to display potent toxicity against several insect species. In the current study, we aimed to investigate the effect of the methyl benzoate compounds (1–17) on PON1 activity. Methyl benzoate compounds inhibited PON1 with KI values ranging from 25.10 ± 4.73 to 502.10 ± 64.72 μM. Compound 10 (methyl 4-amino-2-bromo benzoate) showed the best inhibition (KI = 25.10 ± 4.73 μM). Furthermore, using the ADME-Tox, Glide XP, and MM-GBSA tools of the Schrödinger Suite 2021-4, a complete ligand–receptor interaction prediction was performed to characterize the methyl benzoates (1–17), probable binding modalities versus the PON1. © 2022 Wiley Periodicals LLC.