Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies

Abstract

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.

Analogues of a Cyclic Antimicrobial Peptide with a Flexible Linker Show Promising Activity against Pseudomonas aeruginosa and Staphylococcus aureus

“…The development of antibiotics is one of the greatest accomplishments in modern medicine, treating potentially fatal infections [ 1 ]. Nevertheless, the widespread use of antibiotics has led to the selection of resistant isolates, which in turn has resulted in the emergence of multi-drug resistant microorganisms capable of surviving treatment with most or all antibiotics [ 2 ]. Of dire importance is the development and prevalence of multidrug resistance in Gram-negative species, such as Klebsiella pneumonia , Acinetobacter baumannii , and Eschericia coli , where pan-resistance is now observed [ 3 ].…”

Cheminformatic Characterization of Natural Antimicrobial Products for the Development of New Lead Compounds

“…However, antibacterial agents have been reported to deviate from these rules as marketed antibacterial drugs have higher molecular weights than other drugs [ 58 , 59 ]. Furthermore, most marketed antibacterial agents like streptogramins, macrolides, and daptomycin, commonly used against Gram-positive bacteria, possess larger MW than those used against Gram-negative groups [ 59 , 60 ]. However, few Gram-negative bacteria drugs are characterized by substantially high MW.…”

Antibacterial activities of honey against Escherichia coli and Staphylococcus aureus: A potential treatment for bacterial infections and alternative to antibiotics

“…Globally, honey has been used to cure infectious diseases due to its potent medicinal activity [4][5] . Given the escalating issue of antimicrobial resistance (AMR), there is an urgent need to promote drug discovery from natural products [6][7][8][9][10] . The inappropriate use of conventional antibiotics in humans, animals, and the environment have all contributed to the development and spread of AMR [11][12][13][14][15][16][17] .…”

“…The inappropriate use of conventional antibiotics in humans, animals, and the environment have all contributed to the development and spread of AMR [11][12][13][14][15][16][17] . Antimicrobial resistance is a global public health problem that should be addressed using various strategies that include promoting drug discovery [7,9,[18][19][20][21][22][23][24] and implementing antimicrobial stewardship programmes [25][26][27][28][29][30][31][32][33][34][35] . Some bacteria including Escherichia coli (E. coli) and Staphylococcus aureus(S. aureus) cause most infections that lead to increased morbidity and mortality [36][37][38][39] .…”