Multicomponent catalyst-free regioselective synthesis and binding studies of 3-aroyl-2-methylimidazo[1,2-a]pyrimidines with BSA using biophysical and computational techniques

Abstract

A facile and environmentally benign protocol for regioselective synthesis of diversely substituted imidazo[1,2-a]pyrimidines 5a–h has been described via multicomponent reaction of unsymmetrical β-diketones 1, N-bromosuccinimide 2 and 2-aminopyrimidine 4 in DCM. The reaction proceeds through in situ formation of α-bromo-β-diketones 3 and their ensuing condensation with 2-aminopyrimidine without the need of any organic or inorganic catalyst. The structure of the regioisomeric product was characterized by ¹H, ¹³C NMR, heteronuclear 2D NMR and HRMS studies. The present protocol offers several advantages such as avoidance of metal-based and toxic catalysts, broad substrate scope with respect to substitutions on β-diketones, operational simplicity, easy work-up and high yields. Computational molecular docking studies were carried out to examine the interaction of imidazo[1,2-a]pyrimidines with bovine serum albumin (BSA). Moreover, different spectroscopic approaches viz. UV-visible, steady-state fluorescence and competitive displacement assays were carried out to investigate the binding mechanisms of imidazo[1,2-a]pyrimidines (5c, 5e and 5h) with BSA. The results thus obtained revealed that imidazo[1,2-a]pyrimidines showed moderate binding with BSA through a static quenching mechanism and compound 5e had more affinity to bind in site I of BSA.