Alkoxyphenylthiazoles with broad-spectrum activity against multidrug-resistant gram-positive bacterial pathogens.
ElAwamy M, Mohammad H, Hussien A, Abutaleb NS, Hagras M, Serya RAT, Taher AT, Abouzid KA, Seleem MN, Mayhoub AS.
With the continued rise of antibiotic resistance and reduced susceptibility to almost all front-line antibiotics, multidrug-resistant Gram-positive bacterial infections represent an incessant threat to healthcare providers. This study presents a new series of phenylthiazole compounds where two active moieties were combined into one scaffold. The antibacterial activity of the hybrid structures extended to include several clinically-relevant multi-drug resistant pathogens including methicillin-resistant and vancomycin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, vancomycin-resistant enterococci, cephalosporin-resistant and methicillin-resistant Streptococcus pneumoniae, and Listeria monocytogenes. In addition, the most potent compounds, 16a and 17a, exhibited a fast bactericidal mode of action in vitro with low susceptibility to induce bacterial resistance. In addition to its potent spectrum of activity against Gram-positive bacterial pathogens, compound 17a was found to be metabolically stable in rats, with a half-life of 4 h.