Catalyst-free synthesis of imidazo[5,1-b ]quinazolines and their antimicrobial activity

In this study, imidazo[5,1-b]quinazoline derivatives 4(a-t) were synthesized via a three-component reac-tion of 5-aminoimidazole-4-carbonitrile, 1,3-cyclohexanedione derivatives and various aromatic aldehydes by employing glacial acetic acid as a reaction medium. This catalyst-free approach affords mild reaction conditions and has operational simplicity resulting in excellent yield in a shorter reaction time without any chromatographic separation method. All the synthesized compounds were screened for their antimi-crobial activity against the pathogenic strains. The compounds 4c and 4e exhibit a more promising (MIC = 25 mu g/mL) against S. pyogenes and E. coli bacterial strains than the standard drug ampicillin (MIC = 100 mu g/mL) and chloramphenicol (MIC = 50 mu g/mL) respectively. Compounds 4c, 4h, 4k and 4r showed pronounced antifungal activity (MIC = 250 mu g/mL) against C. albicans compared to the standard drug griseofulvin (MIC = 500 mu g/mL). Further, compound 4k was found to have good antimalarial inhibition (IC50 = 0.28 mu g/mL) against P. falciparum, similar to the standard drug quinine (IC50 = 0.27 mu g/mL). Bind-ing interactions of 4e in the active site of E. coli DNA gyrase (PDB ID: 1KZN) showed good interaction with the target protein. Potent antimicrobial active compounds 4c, 4e and 4k showed drug-likeness with a good ADME profile.(c) 2023 Elsevier B.V. All rights reserved.