Alkoxyphenyithiazoles with broad-spectrum activity against multidrug-resistant gram-positive bacterial pathogens

作者：ElAwamy Moustafa; Mohammad Haroon; Hussien Abdelrahman; Abutaleb Nader S; Hagras Mohamed; Serya Rabah A T; Taher Azza T; Abouzid Khaled A M; Seleem Mohamed N^*; Mayhoub Abdelrahman S^*

来源：European Journal of Medicinal Chemistry, 2018, 152: 318-328.

DOI：10.1016/j.ejmech.2018.04.049

• Antibiotic resistance
• Vancomycin-resistant Enterococci (VRE)
• Methicillin-resistant Staphylococcus aureus (MRSA)
• Pharmacokinetics

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.

• 出版日期2018-5-25