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

oleh: Povilas Kavaliauskas, Birutė Grybaitė, Rita Vaickelionienė, Birutė Sapijanskaitė-Banevič, Kazimieras Anusevičius, Agnė Kriaučiūnaitė, Gabrielė Smailienė, Vidmantas Petraitis, Rūta Petraitienė, Ethan Naing, Andrew Garcia, Vytautas Mickevičius

Format: Article
Diterbitkan: MDPI AG 2023-01-01

Deskripsi

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 <i>S. aureus,</i> as well as emerging fungal pathogens. The 4-substituted thiazoles <b>3h</b>, and <b>3j</b> with naphthoquinone-fused thiazole derivative <b>7</b> with excellent activity against methicillin and tedizolid/linezolid-resistant <i>S. aureus</i>. Moreover, compounds <b>3h</b>, <b>3j</b> and <b>7</b> showed favourable activity against vancomycin-resistant <i>E. faecium</i>. Compounds <b>9f</b> and <b>14f</b> showed broad-spectrum antifungal activity against drug-resistant <i>Candida</i> strains, while ester <b>8f</b> showed good activity against <i>Candida auris</i> which was greater than fluconazole. Collectively, these data demonstrate that <i>N</i>-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.