Synthesis, in vitro bio-evaluation, and molecular docking study of thiosemicarbazone-based isatin/bis-Schiff base hybrid analogues as effective cholinesterase inhibitors
2023; Elsevier BV; Volume: 1284; Linguagem: Inglês
10.1016/j.molstruc.2023.135351
ISSN1872-8014
AutoresShoaib Khan, Hayat Ullah, Rafaqat Hussain, Yousaf Khan, Misbah Khan, Mehmand Khan, Abdul Sattar, Muhammad Saleem Khan,
Tópico(s)Enzyme function and inhibition
ResumoAnalogues of isatin/bis-Schiff bases based on thiocarbohydrazone (1–16) were synthesized, characterised using various methods like NMR and HR-ESI-MS, and then tested against the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All analogues showed good inhibitory potentials ranging from 0.20 ± 0.05 to 7.40 ± 0.20 M (for AChE) and 0.50 ± 0.05 to 9.40 ± 0.10 M (for BuChE) as compared to the reference drug Donepezil (IC50 = 2.16 ± 0.12 & 4.5 ± 0.11 M respectively). Analogue 1 was shown to be the most effective inhibitor of the AChE and BuChE enzymes among the synthesised analogues. The reason for Analogue 1 may be due to the role played by oxygen and the nitro motif in H-bonding with the active sites of AChE and BuChE enzymes. A structure–activity relationship (SAR) was developed based on nature, position, number, and the electron-donating and -withdrawing effects of substitution(s) on phenyl rings. Molecular docking studies were used to describe the binding interactions of the most active inhibitors with the active sites of AChE and BuChE.
Referência(s)