Acetylphenyl-substituted imidazolium salts: synthesis, characterization, in silico studies and inhibitory properties against some metabolic enzymes

Herein, we present how to synthesize thirteen new 1-(4-acetylphenyl)-3-alkylimidazolium salts by reacting 4-(1-H-imidazol-1-yl)acetophenone with a variety of benzyl halides that contain either electron-donating or electron-withdrawing groups. The structures of the new imidazolium salts were conformed using different spectroscopic methods (H-1 NMR, C-13 NMR, F-19 NMR, and FTIR) and elemental analysis techniques. Furthermore, these compounds' the carbonic anhydrase (hCAs) and acetylcholinesterase (AChE) enzyme inhibition activities were investigated. They showed a highly potent inhibition effect toward AChE and hCAs with K-i values in the range of 8.30 & PLUSMN; 1.71 to 120.77 & PLUSMN; 8.61 nM for AChE, 16.97 & PLUSMN; 2.04 to 84.45 & PLUSMN; 13.78 nM for hCA I, and 14.09 & PLUSMN; 2.99 to 69.33 & PLUSMN; 17.35 nM for hCA II, respectively. Most of the synthesized imidazolium salts appeared to be more potent than the standard inhibitor of tacrine (TAC) against AChE and Acetazolamide (AZA) against CA. In the meantime, to prospect for potential synthesized imidazolium salt inhibitor(s) against AChE and hCAs, molecular docking and an ADMET-based approach were exerted.

Journal

MOLECULAR DIVERSITY

Year

2023

Volume

27

Issue

6

Pages

2767-2787

ISSN

1381-1991

eISSN

1573-501X

DOI

10.1007/s11030-022-10578-3

WoS UID

WOS:000898457600001