Benzimidazolium salts bearing ester group: Synthesis, characterization, crystal structure, molecular docking studies, and inhibitory properties against metabolic enzymes

In this work, the synthesis of several unsymmetrical benzimidazolium salts with an ester (2-ethoxy-2-oxoethyl) group on the nitrogen atom is described. The structures of all compounds were fully characterized by spectroscopic (1H, 1 H, 13 C NMR, FTIR) and analytical (elemental analysis) methods. However, single-crystal X-ray diffraction analysis elucidated the molecular and crystal structures of compounds 1a and 1c . Asymmetric units of both crystal structures contain two crystallographically independent molecules and two bromide anions. All compounds exhibited substantial inhibition against the cytosolic carbonic anhydrase isoforms (hCA I and hCA II) and acetylcholinesterase (AChE) with Ki i values 51.00-45.18 nM, 46.94-305.65 nM, and 17.57-65.68 nM, respectively. Notably, compound 1d showed extreme inhibitory effect against hCA I with 51.00+5.31 +5.31 nM (AZA: 275.44+13.32 +13.32 nM), hCA II with 46.94+5.44 +5.44 nM (AZA: 236.55+17.88 +17.88 nM) and AChE with 17.57+3.14 +3.14 nM (TAC: 80.44+6.88 +6.88 nM). In silico approach showed that compound 1d could form stable complexes with target enzymes with a different binding affinity (BE:9.01 kcal/mol for AChE;-7.22 kcal/mol for hCA II and-6.51 kcal/mol for hCA I). The results supported the medical potential of benzimidazolium salts containing ester group. They significantly lighted our knowledge about the chemistry of side groups on phenyl ring especially in the para position as compared to ortho and meta positions.

Dergi

JOURNAL OF MOLECULAR STRUCTURE

Yıl

2025

Cilt

1322

ISSN

0022-2860

eISSN

1872-8014

DOI

10.1016/j.molstruc.2024.140342

WoS UID

WOS:001339274400001