Synthesis and Development of N -2,5-Dimethylphenylthioureido Acid Derivatives as Scaffolds for New Antimicrobial Candidates Targeting Multidrug-Resistant Gram-Positive Pathogens.

The growing antimicrobial resistance to last-line antimicrobials among Gram-positive pathogens remains a major healthcare emergency worldwide. Therefore, the search for new small molecules targeting multidrug-resistant pathogens remains of great importance. In this paper, we report the synthesis and in vitro antimicrobial activity characterisation of novel thiazole derivatives using representative Gram-negative and Gram-positive strains, including tedizolid/linezolid-resistant as well as emerging fungal pathogens. The 4-substituted thiazoles , and with naphthoquinone-fused thiazole derivative with excellent activity against methicillin and tedizolid/linezolid-resistant . Moreover, compounds , and showed favourable activity against vancomycin-resistant . Compounds and showed broad-spectrum antifungal activity against drug-resistant strains, while ester showed good activity against which was greater than fluconazole. Collectively, these data demonstrate that -2,5-dimethylphenylthioureido acid derivatives could be further explored as novel scaffolds for the development of antimicrobial candidates targeting Gram-positive bacteria and drug-resistant pathogenic fungi.