Synthesis, in vitro biological evaluation and in silico molecular docking study of hydroxy‑quinoline based sulfonohydrazide derivatives as potential acetylcholinesterase and butyrylcholinesterase inhibitors
No Thumbnail Available
Date
2024-02
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Elsevier
Series Info
Journal of Molecular Structure;1306 (2024) 137884
Scientific Journal Rankings
Abstract
A series of hydroxy‑quinoline-based sulfonohydrazide derivatives (1–16) were synthesized and their structures
were elucidated by using various spectroscopic tools including 1
HNMR, 13CNMR and HREI-MS and evaluated
against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All synthesized derivatives
showed the varied range of AChE and BuChE activities having IC50 values ranging from 0.20 ± 0.01 to 11.60 ±
0.20 µM (against AChE) and 0.80 ± 0.05 to 22.70 ± 0.30 µM (against BuChE) as compared to standard drug
Donepezil (IC50 = 2.16 ± 0.12 µM & 4.5 ± 0.11 µM, respectively). Among the series, compounds 1, 8, and 10
were identified to be most potent, even more, active than standard drug having IC50 values of 0.40 ± 0.05, 0.20
± 0.01, 0.70 ± 0.05 µM (against AChE) and 0.80 ± 0.05, 0.80 ± 0.05, 2.10 ± 0.10 µM (against BuChE)
respectively. Based on the substitution pattern around the aryl ring, structure-activity relationship (SAR) analysis
was conducted for all synthesized derivatives. Additionally, the molecular docking method was created to
investigate the mechanism of interactions between the scaffolds that are most active and the active sites of
specific AChE and BuChE enzymes.
Description
Keywords
Acetylcholinesterase; Butyrylcholinesterase and molecular docking; Hydroxy-quinoline; Sulfonohydrazide