Halogenation of biotin protein ligase inhibitors improves whole cell activity against Staphylococcus aureus

We report the synthesis and evaluation of 5-halogenated-1,2,3-triazoles as inhibitors of biotin protein ligase from Staphylococcus aureus. The halogenated compounds exhibit significantly improved antibacterial activity over their nonhalogenated counterparts. Importantly, the 5-fluoro-1,2,3-triazole compound 4c displays antibacterial activity against S. aureus ATCC49775 with a minimum inhibitory concentration (MIC) of 8 μg/mL.Ashleigh S. Paparella, Kwang Jun Lee, Andrew J. Hayes, Jiage Feng, Zikai Feng, Danielle Cini, Sonali Deshmukh, Grant W. Booker, Matthew C. J. Wilce, Steven W. Polyak and Andrew D. Abel