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Infections caused by multidrug-resistant bacterial and fungal pathogens represent a significant global health concern, contributing to increased morbidity and mortality rates. Therefore, it is crucial to develop novel compounds targeting drug-resistant microbial strains. Herein, we report the synthesis of amino acid derivatives bearing an incorporated 4-hydroxyphenyl moiety with various substitutions. The resultant novel 3-((4-hydroxyphenyl)amino)propanoic acid derivatives <b>2</b>–<b>37</b> exhibited structure-dependent antimicrobial activity against both ESKAPE group bacteria and drug-resistant <i>Candida</i> species. Furthermore, these derivatives demonstrated substantial activity against <i>Candida auris</i>, with minimum inhibitory concentrations ranging from 0.5 to 64 µg/mL. Hydrazones <b>14</b>–<b>16</b>, containing heterocyclic substituents, showed the most potent and broad-spectrum antimicrobial activity. This activity extended to methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) with MIC values ranging from 1 to 8 µg/mL, vancomycin-resistant <i>Enterococcus faecalis</i> (0.5–2 µg/mL), Gram-negative pathogens (MIC 8–64 µg/mL), and drug-resistant <i>Candida</i> species (MIC 8–64 µg/mL), including <i>Candida auris</i>. Collectively, these findings underscore the potential utility of the novel 3-((4-hydroxyphenyl)amino)propanoic acid scaffold for further development as a foundational platform for novel antimicrobial agents targeting emerging and drug-resistant bacterial and fungal pathogens.