The emergence of multidrug-resistant pathogens that are resistant to most currently available antibiotics is a significant clinical problem. The development of new antibacterial agents and novel approaches is therefore extremely important. Due to the emergence of new resistance, a strategy of combination of two different drugs in one molecule has emerged (hybrid molecules). A series of new hybrid structures containing fluoroquinolone (ciprofloxacin) and aminoglycoside (neomycin) antibiotics linked via 1,2,3-triazole moiety were designed and synthesized, and their antibacterial activities were determined against both Gram-negative and Gram-positive bacteria, including resistant strains. selected hybrid structures have high potency against both Gram negative and Gram-positive bacteria including MRSA and strains harboring either the monofunctional APH(3′) enzyme or the bifunctional AAC(6′)/APH(2′′) enzyme. We also show that new hybrids exhibit the dual mode of action by inhibiting both targets: bacterial protein synthesis and topoisomerase/ gyrase.
- Significantly more potent than the parent NeoB, (against Gram-negative bacteria and Gram positive MRSA)
- Hybrids inhibited bacterial protein synthesis with potencies like or better than that of NeoB
- Significant delay of resistance formation in both Gram-negative and Gram positive bacteria to the treatment with hybrid in comparison to that of each drug alone
Applications and Opportunities
- New antibacterial agent