Screening of in vitro and in silico effect of Fluorophenylthiourea compounds on glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase enzymes

Yildiz M. L., Demir Y., KÜFREVİOĞLU Ö. İ.

JOURNAL OF MOLECULAR RECOGNITION, cilt.35, sa.12, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 35 Sayı: 12
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/jmr.2987
  • Dergi Adı: JOURNAL OF MOLECULAR RECOGNITION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Communication Abstracts, EMBASE, MEDLINE, Metadex, Civil Engineering Abstracts
  • Atatürk Üniversitesi Adresli: Evet

Özet

Inhibition studies of enzymes in the pentose phosphate pathway (PPP) have recently emerged as a promising technique for pharmacological intervention in several illnesses. Glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) are the most important enzymes of the PPP. For this purpose, in the current study, we examined the effect of some fluorophenylthiourea on G6PD and 6PGD enzyme activity. These compounds exhibited moderate inhibitory activity against G6PD and 6PGD with K-I values ranging from 21.60 +/- 8.42 to 39.70 +/- 11.26 mu M, and 15.82 +/- 1.54 to 29.97 +/- 5.72 mu M, respectively. 2,6-difluorophenylthiourea displayed the most potent inhibitory effect for G6PD, and 2-fluorophenylthiourea demonstrated the most substantial inhibitory effect for 6PGD. Furthermore, the molecular docking analyses of the fluorophenylthioureas, competitive inhibitors, were performed to understand the binding interactions at the enzymes' binding site.