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

The novel sulfonamide substitute 1,4-dihydropyridine derivatives were synthesized by the method of Hantzsch reaction. They have been characterized by FT-IR spectroscopy, H-1-NMR, C-13-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 mu M, K-i: 5.43 mu M). 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 ( increment E = 3.12 eV) were calculated for compound (1).

Automated summary

A series of novel sulfonamide substitute 1,4-dihydropyridine derivatives were synthesized by Hantzsch reaction and characterized by various spectroscopic techniques. The antioxidant enzyme PON1 plays important roles in cardiovascular systems. The purified enzyme showed inhibition by all the synthesized compounds, with compound (1) exhibiting the best inhibition effect (IC50: 8.04 μM, Ki: 5.43 μM). Compound (1) also demonstrated free radical scavenging activity of 20.16 mg/mL and a drug score value of 0.13. Molecular docking revealed the lowest binding energy (-1.31 kcal/mol) and the lowest LUMO-HOMO gap (increment E = 3.12 eV) for compound (1) against PON1 enzyme.