Design, synthesis, and biological evaluation of 3-phenylimidazo[1,2-a]pyridine derivatives as diverse enzyme inhibitors

Abstract

This study presents the single-step synthesis of a variety of 3-phenylimidazo[1,2-a]pyridine derivatives 1-24 by reacting different phenacyl bromides with 2-aminopyridine in the presence of DABCO (1,4-diazabicyclo[2.2.2]octane) as a base. Compounds were characterized by spectroscopic techniques to confirm their structures. All synthetic derivatives were evaluated against important metabolic drug targets, including human carbonic anhydrase I and II, alpha-glucosidase, and alpha-amylase enzymes. Pertinent to mention that all the synthetic analogs revealed potent inhibitory strength with Ki values in the range of 104.36-439.41 nM against hCA-I and 119.46-472.35 nM against hCA-II in comparison with the standard acetazolamide Ki = 466.53 +/- 41.22 nM (for hCA-I) and Ki = 481.18 +/- 33.05 nM (for hCA-II). All compounds showed potent inhibitory activity against alpha-glucosidase enzyme with IC50 value 247.50-784.32 nM, compared to the standard acarbose = 22,800 nM. In addition, compounds were also identified as potent inhibitors of alpha-amylase with an IC50 value of 342.67-1011.53 nM compared to the standard acarbose = 10,000 nM. In silico studies of the potential compounds 8, 13, 15, 19, 20, and 21 against hCA-I, hCA-II, alpha-glycosidase, and alpha-amylase were performed to assess the enzyme-ligand interactions with the residues of the active-site target enzymes.