Fluorinated benzimidazolium salts: Synthesis, characterization, molecular docking studies and inhibitory properties against some metabolic enzymes

Abstract

Here, a number of symmetric and unsymmetric N-heterocyclic carbene (NHC) precursors based on benzimidazol-2-ylidene are synthesized. The N-benzyl substituent in these compounds has an electron-withdrawing group (F) at the para position. The structure of these compounds was characterized using elemental analysis and various spectroscopic methods (FTIR and NMR). The molecular and crystal structures of compound 1f and compound 1h were unambiguously elucidated through single-crystal X-ray diffraction analysis. According to the X-ray studies, compound 1f exhibits the formation of a U-shaped molecule whereas compound 1h has a Z-shape formation. In addition, the enzyme inhibition activities of these compounds were investigated against acetylcholinesterase (AChE) and carbonic anhydrases (hCAs). They showed a highly potent inhibition effect on AChE and hCAs (Ki values are in the range of 14.84±1.91 to 174.80±23.60 nM for AChE, 22.41±1.93 to 188.67±27.05 nM for hCA I and 35.29±7.21 to 136.55±17.61 nM for hCA II). These results may contribute to the design and development of new drug candidates, particularly for treatment of some widespread disorders displayed in the world including Alzheimer's disease and glaucoma.