Synthesis, Characterization and Biological Evaluations of New Imidazo[4,5-a]Acridines as Potential Antibacterial Agents

Abstract

The significance of bacterial infections and the early success achieved with some antibiotic drugs have prompted the search for new antibacterial agents. Some new derivatives of 3H-imidazo[4,5-a]acridines are introduced as new powerful antibacterial agents against Gram-positive species. The reaction of N-alkyl-5-nitrobenzimidazoles with arylacetonitriles under basic conditions led to the synthesis of 3H-imidazo[4′,5′:3,4]benzo[c]isoxazoles. Rearrangement of the latter compounds in concentrated sulfuric acid containing nitrous acid gave imidazo[4,5-a]acridones. 3H-imidazo[4,5-a]acridines were obtained by reaction of imidazo[4,5-a]acridones in boiling POCl₃. Finally, new compounds were synthesized from the reaction of 3H-imidazo[4,5-a]acridine derivatives with aromatic amines in high yields. All new compounds were fully characterized by elemental analysis, IR, NMR and mass spectroscopy data. Antibacterial activity of the new compounds was tested against a panel of strains of Gram-negative and Gram-positive bacteria species and the corresponding minimum bactericidal concentration (MBC) values were determined. Results of the antimicrobial screening tests showed that new compounds are very effective against Gram-positive bacteria and their MBC values are comparable with those of well-known antibacterial agents such as cephalexin.