<i>In vitro</i> inhibition potency of malononitrile derivatives on the activity of two pentose phosphate pathway enzymes: accompanied by molecular docking evaluation

Kesebir A. O., Dagalan Z., GÜLLER P., NİŞANCI B., KÜFREVİOĞLU Ö. İ.

ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES, cilt.80, sa.1-2, ss.33-40, 2025 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 80 Sayı: 1-2
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1515/znc-2023-0164
  • Dergi Adı: ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.33-40
  • Anahtar Kelimeler: inhibition, malononitrile derivatives, pentose phosphate pathway, structure-activity relationship
  • Atatürk Üniversitesi Adresli: Evet

Özet

Many disorders, including cancer and malaria, could be targeted via the pentose phosphate pathway (PPP), whose products are key in biosynthetic reactions in cells. The goal of this study was to find new PPP inhibitors. The inhibition effects of malononitrile derivatives on Glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) were analyzed through in vitro experiments. Besides, molecular docking studies were performed to predict the interactions having role in inhibition of compounds. Ki constants of derivatives were found between 4.24 +/- 0.46-69.63 +/- 7.75 mu M for G6PD and 1.91 +/- 0.12-95.07 +/- 11.08 mu M for 6PGD. Derivatives indicated non-competitive inhibition on both enzymes except for compound 4. The findings of the molecular docking studies revealed that free-binding energy estimations agreed with in vitro data. The structure of these malononitrile derivatives may guide for drug discovery in targeting the PPP.