Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies

Over the past century, a multitude of derivatives of structural scaffolds with established antimicrobial potential have been prepared and tested, and a variety of new scaffolds have emerged. The effectiveness of antibiotics, however, is in sharp decline because of the emergence of drug-resistant microorganisms. The prevalence of drug resistance, both in clinical and community settings, is a consequence of bacterial ingenuity in altering pathways and/or cell morphology, making it a persistent threat to human health. The fundamental ability of pathogens to survive in a multitude of habitats can be triggered by recognition of chemical signals that warn organisms of exposure to a potentially harmful environment. Host immune defenses, including reactive oxygen intermediates and antibacterial substances, are among the multitude of chemical signals that can subsequently trigger expression of phenotypes better adapted for survival in that hostile environment. Thus, resistance development appears to be unavoidable, which leads to the conclusion that developing an alternative perspective for treatment options is vital. This review will discuss emerging medicinal chemistry approaches for addressing the global multidrug resistance in the 21st century.