Phenylthiazoles with potent & optimum selectivity toward .

() is one of the most threatening bacteria globally, causing high mortality and morbidity in humans and animals, and is considered a public health threat that requires urgent and aggressive action. Interruption of the human gut microbiome and the development of antibiotic resistance urgently require development and synthesis of effective alternative antibiotics with minimal effects on the normal gut microbial flora. In this study, cyclization of the aminoguanidine head to the thiazole nucleus while maintaining its other pharmacophoric features leads to selective targeting of as shown in the graphical abstract. The most promising compound, 5, was significantly more efficient than vancomycin and metronidazole against six strains of with MIC values as low as 0.030 μg mL. Additionally, compound 5 was superior to vancomycin and metronidazole, showing no inhibition toward nine tested strains of the normal human gut microbiota (>64 μg mL). The high safety profile of compound 5 was also observed with two cell lines HRT-18 and Vero cells.