Synthesis and Biological Evaluation of Benzoxazolone-Thiosemicarbazide, 1,2,4-Triazole, 1,3,4-Thiadiazole Derivatives as Cholinesterase Inhibitors

KOÇAK ASLAN E., SAĞLIK B. N., ÖZKAY Y., PALASKA E.

CHEMISTRYSELECT, cilt.8, sa.35, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 8 Sayı: 35
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/slct.202302069
  • Dergi Adı: CHEMISTRYSELECT
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Anadolu Üniversitesi Adresli: Evet

Özet

In this study, a new series of benzoxazolone-thiosemicarbazide/1,2,4-triazole/1,3,4-thiadiazole hybrids were designed and synthesized. The structures of novel compounds were elucidated by spectral methods (IR, 1H-NMR, 13C-NMR, ESI-MS) and elemental analyses. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition activity of the compounds were investigated using in vitro Ellman method using donepezil and tacrin as the standards. Although none of compounds showed significant inhibitor activity on BuChE, compounds 2 c, 3 a, 4 a and 5 b displayed good inhibitory activities on AChE with IC50 values of 0.031, 0.049, 0.117 and 0.085 & mu;g/mL, respectively. Molecular docking studies were carried out performed to the interactions with the active site of the enzyme (PDB:4EY7) and enzyme kinetics studies were performed for the most potent AChE inhibitor compound 2 c. In this study, benzoxazolone-thiosemicarbazide/1,2,4-triazole/1,3,4-thiadiazole derivatives were synthesized and determined for their in vitro cholinesterase inhibitory activity. The most active derivative against cholinesterase enzyme was found and enzyme kinetic studies and molecular modeling studies were performed.image