Synthesis, cholinesterase inhibitory activity, and in silico studies of novel pyrazolopyrazine derivatives as selective acetylcholinesterase inhibitors
JOURNAL OF RESEARCH IN PHARMACY, cilt.30, sa.5, ss.1352-1367, 2026 (ESCI, TRDizin)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 30 Sayı: 5
- Basım Tarihi: 2026
- Doi Numarası: 10.12991/jrespharm.1897524
- Dergi Adı: JOURNAL OF RESEARCH IN PHARMACY
- Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), TR DİZİN (ULAKBİM)
- Sayfa Sayıları: ss.1352-1367
- Van Yüzüncü Yıl Üniversitesi Adresli: Evet
Özet
In this study, a series of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives (8a-i) were synthesized. The molecular structures of the synthesized compounds were determined by 1H NMR, 13C NMR, and LC-MS/MS analyses. The inhibitory activities of the compounds against AChE and BChE were evaluated. Compound 8e exhibited the highest inhibitory activity against AChE, with an IC50 value of 3.795 ± 0.057 µM, whereas compound 8h showed the highest inhibitory activity against BChE, with an IC50 value of 15.484 ± 0.188 µM. Docking scores for compound 8e and donepezil in the 4EY7 structure were −8.39 and −11.06 kcal/mol, respectively, whereas in the 4BDS structure, docking scores for compound 8h and donepezil were −8.08 and −8.97 kcal/mol. In addition, the most potent acetylcholinesterase inhibitor, 8e, exhibited interaction patterns comparable to those of donepezil within the AChE active site. Docking analyses of all compounds were performed on the AChE and BChE enzymes, and structure-activity relationships were evaluated. Moreover, the drug-likeness, ADME, and toxicity profiles of the compounds 8a-i and donepezil were predicted.