Synthesis, structural analysis, antimicrobial evaluation and synergistic studies of imidazo[1,2-a]pyrimidine chalcogenides

Abstract

A series of mixed aryl/heteroaryl/alkyl imidazo[1,2-a]pyrimidine chalcogenides have been synthesized by nucleophilic substitution reaction on 2-(chloromethyl)imidazo[1,2-a]pyrimidine (3) with corresponding aryl/heteroaryl selenols and alkyl/aryl thiolates, generated in situ using simple and greener methodologies. Symmetrical chalcogenides were prepared by the reaction of sodium hydrogen chalcogenides with precursor 3 followed by characterization using NMR and mass spectrometry. The X-ray crystal structure was determined for compound 6 and the experimental structural parameters were compared with the theoretical values calculated at the B3LYP 6-31 G(d) level of energy. The newly synthesized compounds were evaluated for their antimicrobial activities against various fungal and bacterial strains. Compounds 6–9 showed mild antifungal activity against N. crassa, while compound 7 was found to be active against C. keyfer (MIC 18.87 μg mL⁻¹). Interestingly, compound 7 showed antibacterial activity against the strain E. coli (MIC 18.87 μg mL⁻¹). Time kill studies showed that the colony forming units of the strains C. keyfer and E. coli reduced rapidly after treatment with compound 7. Cytotoxicity studies were carried out for compounds 6 and 7 against HeLa cells and Hek-293 cells and exhibited less significant cytotoxicity against both the cell lines. Furthermore, as the synthesized compounds did not display potent efficacy against the tested microbial strains, the active compounds 6 and 7 were investigated for synergistic effects against the growth of C. keyfer and E. coli in combination with well known standard antifungal drug amphotericin B (Amp B) and antibacterial drug rifampicin (RIF) displaying an effective synergy with the used antibiotics.