The development of novel antimicrobial drugs is an essential part of combatting the uprising of antimicrobial resistance. Proper hit-to-lead development is crucially needed. We present a hit-expansion study of -pyrazinyl- and -pyridyl-hydroxybenzamides with a comprehensive determination of structure-activity relationships. The antimicrobial screening revealed high selectivity to staphylococci along with antimycobacterial activity with the best value of 6.25 μg/ml against H37Rv. We proved an inhibition of proteosynthesis and a membrane depolarization of methicillin-resistant . Our results are a good starting point for further development of new antimicrobial compounds, where the next step would be tuning the potential between relatively nonspecific membrane depolarization effect and specific inhibition of proteosynthesis.
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