Infectious
diseases remain significant health concerns worldwide,
and resistance is particularly common in patients with tuberculosis
caused by Mycobacterium tuberculosis. The development
of anti-infectives with novel modes of action may help overcome resistance.
In this regard, membrane-active agents, which modulate membrane components
essential for the survival of pathogens, present attractive antimicrobial
agents. Key advantages of membrane-active compounds include their
ability to target slow-growing or dormant bacteria and their favorable
pharmacokinetics. Here, we comprehensively review recent advances
in the development of membrane-active chemotypes that target mycobacterial
membranes and discuss clinically relevant membrane-active antibacterial
agents that have shown promise in counteracting bacterial infections.
We discuss the relationship
between the membrane properties and the synthetic requirements within
the chemical scaffold, as well as the limitations of current membrane-active
chemotypes. This review will lay the chemical groundwork for the development
of membrane-active antituberculosis agents and will foster the discovery
of more effective antitubercular agents.
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