Using Fragment-Based Approaches to Discover New Antibiotics

Area of Science:

• Drug discovery and development
• Medicinal chemistry
• Antimicrobial resistance

Background:

• Fragment-based lead discovery (FBLD) is a successful strategy for generating drug candidates.
• Conventional high-throughput screening (HTS) has limitations in chemical space sampling and property control.
• Antibiotic development faces challenges due to evolved resistance and strict drug property requirements.

Purpose of the Study:

• To provide an overview of fragment-based approaches for new antibiotic discovery.
• To discuss successful examples of fragment-to-lead development in antibiotics.
• To highlight current challenges and opportunities in FBLD for novel antibiotics.

Main Methods:

• Review of fragment-based screening strategies.
• Analysis of hit-to-lead development case studies for antibiotics.
• Discussion of physicochemical property control in FBLD.

Main Results:

• FBLD enables more efficient exploration of chemical space compared to HTS.
• FBLD allows for better control over drug-like properties of lead candidates.
• Several successful examples of FBLD for antibiotic development were identified.

Conclusions:

• Fragment-based lead discovery is a promising strategy for developing new antibiotics.
• Addressing challenges in FBLD can accelerate the discovery of urgently needed antimicrobial drugs.
• FBLD offers opportunities to overcome the antibiotic resistance crisis.