N-Substituted 9-Aminoacridine Derivatives as Promising Antimicrobial Agents: Synthesis, Characterization, and Structure–Activity Relationship.

Introduction: The increasing prevalence of antimicrobial resistance necessitates development of novel antimicrobial agents with improved efficacy and broader activity spectra. Acridine derivatives particularly 9-aminoacridine have attracted considerable interest as promising antimicrobial pharmacophore. In this study, we have synthesized ten derivatives and evaluated N-substituted 9-aminoacridine derivatives for antibacterial and antifungal activities

Methods: Ten derivatives were synthesized through N-alkylation and characterized using TLC, M.P., UV, FTIR, ¹H-NMR, and FABMS. Antibacterial activity was evaluated against selected Gram-positive and Gram-negative bacterial strains using the agar diffusion method, with Gentamicin as the reference standard. Antifungal activity was assessed against Aspergillus fumigatus, Rhizopus spp., and Candida albicans, using Fluconazole as the reference standard.

Results: Among the synthesized derivatives, PMA exhibited the most potent antibacterial activity, comparable to or greater than Gentamicin against E-coli, Proteus mirabilis, Enterococcus spp., and Staphylococcus aureus. PPA also demonstrated notable antibacterial activity and showed the highest antifungal activity against Rhizopus spp., slightly exceeding that of Fluconazole, while PBrS exhibited comparable antifungal activity. Structure–activity relationship analysis revealed that structural modifications at the 9-amino position significantly influenced antimicrobial potency and activity spectrum.

Conclusion:. Overall, the synthesized ten derivatives of 9-amino Acridine demonstrated promising antimicrobial potential, identifying PMA and PPA as particularly promising candidates for further optimization and evaluation.