1-(2-Hydroxy-5-((trimethylsilyl)ethynyl)phenyl)ethanone based α,β-unsaturated derivatives an alternate to non-sulfonamide carbonic anhydrase II inhibitors, synthesis via Sonogashira coupling, binding analysis, Lipinsk’s rule validation

Abstract

A novel series of silyl-yne containing chalcone derivatives 5a-5j was synthesized by exploiting Sonogashira coupling reaction and Claisen-Schimdt condensation reaction. The synthesized derivative were characterized by spectroscopic and elemental analysis. The selective inhibition of carbonic anhydrases is considered critical in the field of medicinal chemistry because carbonic anhydrases exits in several isoforms. Synthesized compounds were subjected to carbonic anhydrase –II assay. Except 5j, the other derivatives exhibited better potential than standard acetazolamide. Compound 5e was found to be potent derivative in the series with IC50 value 0.054 ± 0.001 µM. Binding analysis revealed that most potent derivative 5e binds in the active site of CA-II and single π-π stacking interaction was observed between ring structure of ligand and Phe129 having bond length 4.90 Å. Pharmacokinetics elicited that compounds obey Lipinski’s rule and show significant drug score.