Advancing cell wall inhibitors towards clinical applications

Area of Science:

• Natural product chemistry
• Medicinal chemistry
• Microbiology

Background:

• Natural products are a significant source of approved drugs, contributing substantial chemical diversity.
• Recent approvals, such as dalbavancin (a semi-synthetic glycopeptide), highlight the continued importance of natural product-derived antibiotics.
• Dalbavancin functions by inhibiting bacterial peptidoglycan biosynthesis through binding to lipid intermediate II (Lipid II).

Purpose of the Study:

• To review the development of dalbavancin, a Lipid II-binding antibiotic.
• To introduce ongoing research into novel Lipid II-binding natural products and derivatives.
• To focus on the properties of NAI-107 and related lantibiotics.

Main Methods:

• Review of preclinical and clinical development history of dalbavancin.
• Characterization of novel natural products and derivatives.
• Screening efforts for new antibiotic candidates.

Main Results:

• Dalbavancin, a second-generation glycopeptide, was approved, demonstrating the success of natural product-derived drugs.
• The study pipeline includes two additional Lipid II-binding natural products or derivatives.
• Focus is placed on NAI-107 and related lantibiotics identified through recent screening.

Conclusions:

• Natural products remain a crucial resource for developing new antibiotics.
• Continued investigation into Lipid II-binding compounds like lantibiotics shows promise for addressing antibiotic resistance.
• The development pipeline includes promising candidates for future antibacterial therapies.