Position switch of phenylthiazoles: novel compounds with promising anti-MRSA USA300

Abstract

The discovery of novel antibacterial agents holds promise in mitigating the escalating threat of antimicrobial resistance (AMR). Guided by the structure-activity relationships (SAR) of our lead compound 1 against MRSA, we developed novel anti-MRSA compounds with a repositioned lipophilic tail from para to meta position. This strategic modification resulted in compounds 10e and 10l exhibiting equivalent activity to lead compound 1 (MIC = 4 µg/ml) against the highly clinically important strain MRSA USA300. Additionally, both compounds demonstrated a low propensity for resistance development and an acceptable cytotoxicity profile. However, their systemic administration was poorly tolerated. The in vivo study in a murine model revealed modest activity in the skin model but an acceptable effect in controlling systemic dissemination.