and Activities of TP0480066, a Novel Topoisomerase Inhibitor, against Neisseria gonorrhoeae.

Gonorrhea is a common, sexually transmitted disease caused by Multidrug-resistant is an urgent threat, and the development of a new antimicrobial agent that functions via a new mechanism is strongly desired. We evaluated the and activities of a DNA gyrase/topoisomerase IV inhibitor, TP0480066, which is a novel 8-(methylamino)-2-oxo-1,2-dihydroquinoline derivative. The MICs of TP0480066 were substantially lower than those of other currently or previously used antimicrobials against gonococcal strains demonstrating resistance to fluoroquinolones, macrolides, β-lactams, and aminoglycosides (MICs, ≤0.0005 μg/ml). Additionally, no cross-resistance was observed between TP0480066 and ciprofloxacin. The frequencies of spontaneous resistance to TP0480066 for ATCC 49226 were below the detection limit (<2.4 × 10) at concentrations equivalent to 32× MIC. TP0480066 also showed potent bactericidal activity and efficacy in a mouse model of infection. These data suggest that TP0480066 is a candidate antimicrobial agent for gonococcal infections.