Design and Evaluation of an Imidazoacridine‐Penicillin Hybrid: A Dual‐Action Strategy Against Multidrug‐Resistant Bacteria

Abstract The alarming rise of multidrug‐resistant pathogens has necessitated novel antibiotic approaches. This study developed an imidazoacridine‐penicillin hybrid combining two distinct mechanisms: β‐lactam‐mediated cell wall disruption and imidazoacridine's DNA intercalation. This rational design aimed to circumvent resistance mechanisms and improve antibacterial efficacy. The target compound was synthesized via an optimized multistep procedure, rigorously characterized by FTIR, NMR, and mass spectrometry. Biological testing revealed exceptional activity against resistant strains, with MIC values lower than conventional antibiotics against MRSA and Pseudomonas aeruginosa . Interestingly, the hybrid also exhibited promising cytostatic activity against cancer cell lines, suggesting potential dual applications. Molecular docking studies with bacterial enzyme 1CEF revealed strong binding (ΔG = −8.8 kcal/mol) through multiple interactions. This work establishes hybrid molecular design as a powerful strategy against antibiotic resistance. The unexpected anticancer activity further highlights its therapeutic potential, warranting further preclinical development as both an antimicrobial and potential anticancer agent.