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

KAYA M. O., Demirci T., Ozdemir O., Calisir U., Sonmez F., Arslan M.

Medicinal Chemistry Research, vol.32, no.5, pp.841-855, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 32 Issue: 5
  • Publication Date: 2023
  • Doi Number: 10.1007/s00044-023-03029-7
  • Journal Name: Medicinal Chemistry Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, Veterinary Science Database
  • Page Numbers: pp.841-855
  • Keywords: PON1, Inhibition, Drug score, Molecular docking, 1, 4-dihydropyridine, PHARMACOLOGICAL-ACTIVITIES, DRUG DISCOVERY, PURIFICATION
  • Kocaeli University Affiliated: Yes


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).