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The drastic increase in the emergence of methicillin and vancomycin resistant S. aureus has resulted in almost negligible treatment options available to tackle these drug-resistant strains and therefore, search for newer antibiotics is essential. In this context, a new series of quaternized fused β-carbolines was synthesized and evaluated for its anti-bacterial potential. Several compounds from the series displayed potent anti-bacterial activity against Gram-positive bacteria including the drug-resistant strains with minimal cytotoxicity and promising bactericidal action., (© 2025 Wiley-VCH GmbH.)