Molecular Docking Studies and the Effect of Fluorophenylthiourea Derivatives on Glutathione-Dependent Enzymes

Demir Y., TÜRKEŞ C., KÜFREVİOĞLU Ö. İ., BEYDEMİR Ş.

Chemistry and Biodiversity, cilt.20, sa.1, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 20 Sayı: 1
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/cbdv.202200656
  • Dergi Adı: Chemistry and Biodiversity
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: Enzyme inhibition, glutathione S-transferase, glutathione reductase, fluorophenylthiourea, CALCIUM-CHANNEL BLOCKERS, IN-SILICO EVALUATION, S-TRANSFERASE, CARBONIC-ANHYDRASE, POTENTIAL ACETYLCHOLINESTERASE, THIOUREA DERIVATIVES, METAL-IONS, REDUCTASE, PURIFICATION, PROTEIN
  • Atatürk Üniversitesi Adresli: Evet

Özet

© 2022 Wiley-VHCA AG, Zurich, Switzerland.Cancer is a serious problem affecting the health of all human societies. Chemotherapy refers to the use of drugs to kill cancer or the origin of cancer. In the past three decades, researchers have studied about proteins and their roles in the production of cancer cells. Glutathione S-transferases (GSTs) are a superfamily of enzymes that play a key role in cellular detoxification, protecting against reactive electrophiles attacks, including chemotherapeutic agents. Glutathione reductase (GR) is an important antioxidant enzyme involved in protecting the cell against oxidative stress. In this current study, GST and GR enzymes were purified from human erythrocytes using affinity chromatography. GR was obtained with a specific activity of 5.95 EU/mg protein and a 52.38 % yield. GST was obtained with a specific activity of 4.88 EU/mg protein and a 74.88 % yield. The effect of fluorophenylthiourea derivatives on the purified enzymes was investigated. Afterward, KI values were found to range from 23.04±4.37 μM–59.97±13.45 μM for GR and 7.22±1.64 μM–41.24±2.55 μM for GST. 1-(2,6-difluorophenyl)thiourea was showed the best inhibition effect for both GST and GR enzymes. The relationships of inhibitors with 3D structures of GST and GR were explained by molecular docking studies.