Synthesis and biological studies of pyrimidine derivatives targeting metabolic enzymes

• Published in: Archiv der Pharmazie (Weinheim) Vol. 357; no. 8; pp. e2300634 - n/a
• Main Authors: Korkusuz, Elif, Sert, Yusuf, Arslan, Seher, Aydın, Hava, Yıldırım, İsmail, Demir, Yeliz, Gülçin, İlhami, Koca, İrfan
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.08.2024; Wiley Subscription Services, Inc
• Subjects: carbonic anhydrase; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; cholinesterase; enzyme inhibition; Life Sciences & Biomedicine; molecular docking; Pharmacology & Pharmacy; Physical Sciences; pyrimidine; Science & Technology; BUTYRYLCHOLINESTERASE; CARBONIC-ANHYDRASE; ANHYDRASE INHIBITORY PROPERTIES; IN-VITRO ANTIBACTERIAL; cholinesterase; ALPHA-GLUCOSIDASE; IDENTIFICATION; molecular docking; enzyme inhibition; ACETYLCHOLINESTERASE; carbonic anhydrase; THIOPYRIMIDINE; OPTIMIZATION; pyrimidine; ALDOSE REDUCTASE
• ISSN: 0365-6233; 1521-4184; 1521-4184
• DOI: 10.1002/ardp.202300634

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. Novel synthesized pyrimidine derivatives were investigated against carbonic anhydrase isoenzymes I and II, acetylcholinesterase, butyrylcholinesterase, α‐glycosidase, and aldol reductase enzymes. The novel pyrimidine derivatives were found to have effective inhibition abilities towards the metabolic enzymes, and their modes of inhibition were evaluated.