Chapter Sixteen - Advances in Inhibitors of Penicillin-Binding Proteins and β-Lactamases as Antibacterial Agents

• Autores: Yong He, Jonathan Lawrence, Christopher Liu, Ning Yin
• Localización: Annual reports in medicinal chemistry, ISSN 0065-7743, Vol 49, 2014, págs. 249-266
• Idioma: inglés
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• Resumen

  • Abstract The continued rise of multidrug-resistant bacterial infections poses a significant threat to public health and has prompted the pharmaceutical industry to reinvest in the discovery of new antibiotics with increased potency and expanded spectrum against these lethal pathogens. Although many excellent antibacterial targets exist, the penicillin-binding proteins remain the most clinically successful and most well-understood antibacterial targets currently by researchers. The classic β-lactam motif continues to be a primary driver in this field with Nth generation β-lactams as a major focus of research. In addition, the evolution of β-lactamase (BL) resistance-particularly in Gram-negative pathogens-has pushed the industry to develop both non-β-lactam inhibitors of PBPs as well as direct inhibitors of the BL enzymes themselves, dosed concurrently with a BL antibiotic. This review will summarize the most recent advances in the development of BL and non-β-lactam PBP inhibitors and the development of inhibitors of the serine and metallo-β-lactamase enzymes for treatment of bacterial infections.