Inhibition of Human Serum Paraoxonase-I with Antimycotic Drugs: In Vitro and In Silico Studies

TÜRKEŞ C., BEYDEMİR Ş.

Applied Biochemistry and Biotechnology, cilt.190, sa.1, ss.252-269, 2020 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 190 Sayı: 1
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1007/s12010-019-03073-3
  • Dergi Adı: Applied Biochemistry and Biotechnology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, Agricultural & Environmental Science Database, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Compendex, EMBASE, Food Science & Technology Abstracts, MEDLINE, Pollution Abstracts, Veterinary Science Database
  • Sayfa Sayıları: ss.252-269
  • Anahtar Kelimeler: Antimycotic drug, Chromatography, HDL, Inhibition, Molecular docking, Paraoxonase
  • Bilecik Şeyh Edebali Üniversitesi Adresli: Evet

Özet

Drugs show their pharmacological effects by inhibiting or activating enzymes. Therefore, enzyme inhibitors have an essential place in the drug design for numerous different sorts of diseases, i.e., cardiovascular, cancer, metabolic, and neurological. The purpose of the current study was to contribute to the growing drug discovery and development area by analyzing functions and drug interactions of paraoxonase-I. For this purpose, the PON1 enzyme was purified from fresh human serum using simple, rapid, and different chromatographic techniques. Then, it was tested for the inhibitory effects of some antimycotic drugs on the PON1. Also, molecular docking analyses of each drug were carried out to determine the binding interactions on the active site of the PON1 enzyme. It was identified that the purified enzyme had the specific activity of 3880.83 EU/mg proteins and the molecular weight of 43 kDa by SDS-PAGE. IC50 values for PON1 were in the range of 0.037 ± 0.001–5.728 ± 0.043 mM. Ki constants for caspofungin acetate, amphotericin B, anidulafungin, and fluconazole were determined to be 0.0105 ± 0.0015 mM, 0.3206 ± 0.0196 mM, 0.1674 ± 0.0233 mM, and 2.5464 ± 0.1655 mM, respectively. The inhibition mechanism of amphotericin B was non-competitive, whereas anidulafungin was mixed type, and the others were competitive.