Benzenesulfonamide derivatives containing imine and amine groups: Inhibition on human paraoxonase and molecular docking studies

IŞIK M., BEYDEMİR Ş., Demir Y., DURGUN M., TÜRKEŞ C., Nasir A., ...Daha Fazla

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, cilt.146, ss.1111-1123, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 146
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.ijbiomac.2019.09.237
  • Dergi Adı: INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, INSPEC, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1111-1123
  • Anahtar Kelimeler: Paraoxonase, Sulfonamide, Inhibition, HUMAN SERUM PARAOXONASE-1, BETA-CARBONIC ANHYDRASE, IN-VITRO, 1 PON1, SULFONAMIDE DERIVATIVES, ACCURATE DOCKING, OXIDATIVE STRESS, ISOFORMS I, PROTEIN, PURIFICATION
  • Anadolu Üniversitesi Adresli: Evet

Özet

Sulfonamides known as inhibitors of many metabolic enzymes have been widely used as antimicrobial drugs for a long time. In the present study, we investigated in vitro inhibitory activities of benzenesulfonamide derivatives on human paraoxonase-I (hPON1). For this aim, PON1 was purified from human serum with a specific activity of 2603.57 EU/mg and 8.34% yield using simple chromatographic methods. The various concentrations of early-synthesized sixteen sulfonamide derivatives were tested on the paraoxonase activity. K-i values of compounds were found in the range of 0.28-357.70 mu M. Compound H4 had the highest inhibitory activity on hPON1 as competitive. Estimated structure-activity relationship (SAR) for compounds was done based on different substituents and their positions in the compounds. Besides, the molecular docking analysis of compound H4 was performed to understand the binding interactions on the active site of the enzyme. According to these experimental results, compound H4 was a potential inhibitor of PON1. (C) 2019 Elsevier B.V. All rights reserved.