Abstract
Antibiotics are potent pharmacological weapons against bacterial pathogens, nevertheless their efficacy is becoming compromised due to the worldwide emergence and spread of multidrug-resistant bacteria or “superbugs”. Antibiotic resistance is rising to such dangerous levels that the treatment of bacterial infections is becoming a clinical challenge. Therefore, urgent action is needed to develop new generations of antibiotics that will help tackle this increasing and serious public health problem. Due to its essential role in bacterial cell division, the tubulin-like protein FtsZ has emerged as a promising target for the development of novel antibiotics with new mechanisms of action. This review highlights the medicinal chemistry efforts towards the identification of small-molecule FtsZ inhibitors with antibacterial activity in the last three years.
Highlights
The discovery of antibiotics unquestionably represented one of the most remarkable scientific breakthroughs of the twentieth century
PC190723 is a benzamide that has potent antibacterial activity against B. subtilis and several strains of S. aureus, which opened the avenue towards the discovery of a new class of small molecules that target FtsZ and inhibit cell division [37]. Even though it was inactive against a number of Gram-negative strains, this benzamide derivative was able to inhibit the growth of B. subtilis and several species of Staphylococci, including MRSA and multidrug-resistant S. aureus (MDRSA), with minimum inhibitory concentration (MIC) values ranging from 1.41 to 2.81 μM (Table 1) [38]
Of the burden is due to bacteria resistant to antibiotics of last resort [75]
Summary
The discovery of antibiotics unquestionably represented one of the most remarkable scientific breakthroughs of the twentieth century. After many years of success in the fight against infectious diseases, the ever-increasing worldwide emergence and spread of “superbugs” (bacteria resistant to most of the antibiotics in current clinical use) is compromising our ability to treat infections. Urgent action must be taken in order to develop new generations of antimicrobial chemical entities with innovative mechanisms of action that will help revitalize the dwindling antibacterial pipeline [15] An example of these novel unconventional targets is FtsZ (filamenting temperature-sensitive protein Z), which, due to its crucial role in the bacterial cell division, has garnered increasing attention as a promising and exciting point of intervention to develop novel antibiotics [16,17,18,19].
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