Synthesis and biological studies of pyrimidine derivatives targeting metabolic enzymes


Korkusuz E., SERT Y., Arslan S., Aydın H., Yıldırım İ., Demir Y., ...Daha Fazla

Archiv der Pharmazie, cilt.357, sa.8, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 357 Sayı: 8
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1002/ardp.202300634
  • Dergi Adı: Archiv der Pharmazie
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, Veterinary Science Database
  • Anahtar Kelimeler: carbonic anhydrase, cholinesterase, enzyme inhibition, molecular docking, pyrimidine
  • Atatürk Üniversitesi Adresli: Evet

Özet

Novel synthesized pyrimidine derivatives were investigated against carbonic anhydrase isoenzymes I and II (hCA I and II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glycosidase, and aldose reductase (AR) enzymes associated with some common diseases such as epilepsy, glaucoma, Alzheimer's disease, diabetes, and neuropathy. When the results were examined, novel synthesized pyrimidine derivatives were found to have effective inhibition abilities toward the metabolic enzymes. IC50 values and Ki values were calculated for each pyrimidine derivative and compared to positive controls. The synthesized novel pyrimidine derivatives exhibited Ki values in the range of 39.16 ± 7.70–144.62 ± 26.98 nM against hCA I, 18.21 ± 3.66–136.35 ± 21.48 nM toward hCA II, which is associated with different pathological and physiological processes, 33.15 ± 4.85–52.98 ± 19.86 nM on AChE, and 31.96 ± 8.24–69.57 ± 21.27 nM on BChE. Also, Ki values were determined in the range of 17.37 ± 1.11–253.88 ± 39.91 nM against α-glycosidase and 648.82 ± 53.74–1902.58 ± 98.90 nM toward AR enzymes. Within the scope of the study, the inhibition types of the novel synthesized pyrimidine derivatives were evaluated.