Arylthiazole antibiotics targeting intracellular methicillin-resistant Staphylococcus aureus (MRSA) that interfere with bacterial cell wall synthesis

作者：Eid Islam; Elsebaei Mohamed M; Mohammad Haroon; Hagras Mohamed; Peters Christine E; Hegazy Youssef A; Cooper Bruce; Pogliano Joe; Pogliano Kit; Abulkhair Hamada S; Seleem Mohamed N^*; Mayhoub Abdelrahman S^*

来源：European Journal of Medicinal Chemistry, 2017, 139: 665-673.

DOI：10.1016/j.ejmech.2017.08.039

• Antibiotic drug resistance
• Caenorhabditis elegans
• Methicillin-resistant Staphylococcus aureus MRSA
• Intracellular infection
• Pharmacokinetics

The promising antibacterial potency of arylthiazole antibiotics is offset by their limited activity against intracellular bacteria (namely methicillin-resistant Staphylococcus aureus (MRSA)), similar to many clinically-approved antibiotics. The failure to target these hidden pathogens is due to the compounds' lack of proper characteristics to accumulate intracellularly. Fine tuning of the size and polar-surface-area of the linking heteroaromatic ring provided a new series of 5-thiazolylarylthiazoles with balanced properties that allow them to sufficiently cross and accumulate inside macrophages infected with MRSA. The most promising compound 4i exhibited rapid bactericidal activity, good metabolic stability and produced over 80% reduction of intracellular MRSA in infected macrophages.

• 出版日期2017-10-20