Design and synthesis of various 1,3,4-oxadiazoles as AChE and LOX enzyme inhibitors

• Published in: Heterocyclic Communications Vol. 29; no. 1; pp. 149 - 60
• Main Authors: Iqbal Javed, Mallhi Ali Imran, ur Rehman Aziz, Al-Mijalli Samiah H., un-Nisa Mehr, Zafar Fatiqa, Shahzad Sohail, Rasool Shahid, Iqbal Munawar, Shah Syed Adnan Ali
• Format: Journal Article
• Language: English
• Published: Berlin Walter de Gruyter GmbH 15.11.2023; De Gruyter
• Subjects: 1,3,4-oxadiazole; acetyl cholinesterase; Chemical synthesis; Enzymes; In vivo methods and tests; Infrared spectroscopy; lipoxygenase; Liquid oxygen; Molecular docking; Molecular structure; NMR; Nuclear magnetic resonance; Oxadiazoles; Pharmacology; Physostigmine; Piperidine; Spectrum analysis; urease
• DOI: 10.1515/hc-2022-0169
• ISSN: 0793-0283

N-Substituted-2-propanamide analogues of 1,3,4-oxadiazole have been synthesized using a multi-step synthetic protocol to explore new therapeutic anti-enzymatic agents. Herein, we have merged sulfonyl, piperidine, oxadiazole and amide into a single unit to synthesize a library of unique compounds, 8a–n. The molecular structures of all synthesized compounds were verified by 13C-NMR, 1H-NMR, HRMS and IR spectroscopy. Furthermore, the compounds were screened for their inhibition potential against acetylcholinesterase (AChE), urease and lipoxygenase (LOX) enzymes. A considerable inhibition potential was observed for three compounds against LOX with quercetin as a reference standard, two compounds against urease with thiourea as a reference standard and two compounds against AChE with eserine as a reference standard. Through molecular docking investigations, we were able to correlate the overall impact and inhibition criteria by the structure–activity relationship via the interactions between synthesized compounds and active sites of enzymes. Pharmacodynamics, pharmacokinetics and in vivo studies may be investigated further for the most active compounds to substantiate them as potential anti-enzymatic medications.