Synthesis, inhibition effects, molecular docking and theoretical studies as Paraoxonase 1 (PON1) inhibitors of novel 1,4-dihydropyridine substituted sulfonamide derivatives

Abstract

The novel sulfonamide substitute 1,4-dihydropyridine derivatives were synthesized by the method of Hantzsch reaction. They have been characterized by FT-IR spectroscopy, 1H-NMR, 13C-NMR, and elemental analysis. PON1 which is an antioxidant enzyme has important functions in cardiovascular systems. The enzyme has been purified using a two-step method such as ammonium sulfate precipitation and sepharose-4B-l-tyrosine-9-aminophenanthrene hydrophobic interaction chromatography. The results demonstrated that all the synthesized compounds inhibited PON1 enzyme. The best inhibition effect was observed in compound (1) for PON1 enzyme (IC50: 8.04 µM, Ki: 5.43 µM). The free radical scavenging for PON1 was discovered as 20.16 mg/mL, while drug score value was reported as 0.13 for compound (1). Furthermore, the lowest binding energy (?1.31 kcal/mol) determined by molecular docking for PON1 enzyme and the lowest LUMO-HOMO gap (?E = 3.12 eV) were calculated for compound (1). © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.