New Cholinesterase inhibitors based on 1,2,4-triazole bearing benzenesulfonohydrazide skeleton: Synthesis, in vitro and in silico studies

• Published in: Results in Chemistry
• Main Author: Othman M.S.; Naz H.; Rahim F.; Ullah H.; Hussain R.; Taha M.; Khan S.; Fareid M.A.; Aboelnaga S.M.; Altaleb A.T.; Iqbal R.; Adnan Ali Shah S.
• Format: Article
• Language: English
• Published: Elsevier B.V. 2024
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85201317446&doi=10.1016%2fj.rechem.2024.101717&partnerID=40&md5=141d17803bd4681d147df0e24821054c

We have synthesized 1,2,4-triazole bearing benzenesulfonohydrazide analogues (1–21), characterized through different spectroscopic techniques such as 1HNMR, 13CNMR, HREI-MS and were evaluated against Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) enzymes. All the newly synthesized analogues showed excellent to good inhibition potential with IC50 values ranged from 0.30 ± 0.050 to 15.21 ± 0.50 µM (against AChE) and 0.70 ± 0.050 to 18.27 ± 0.60 µM (against BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Analogues 2 and 4 which were found inactive against these enzymes. However, analogues 17 (IC50 = 0.30 ± 0.050 and 0.70 ± 0.050 µM) and 13 (IC50 = 0.70 ± 0.05 and 1.70 ± 0.050 µM) were found to have potent inhibitory potentials against the targeted enzymes. Structure-activity relationship was carried out which mainly depends upon the nature, position and numbers of the substitution present on phenyl rings that may be electron withdrawing/donating. Molecular docking study was carried out to know about the binding mode of interaction of the most active site of the synthesized analogues with the targeted enzymes. © 2024 The Author(s)