Recent advances in Fragment-based strategies against tuberculosis

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Infectious Diseases

Background:

• Tuberculosis (TB) is a major global health threat, causing over 1.5 million deaths annually.
• The rise of drug-resistant tuberculosis necessitates the urgent development of new anti-TB drugs.
• Fragment-based drug discovery (FBDD) is a key strategy for identifying novel therapeutic agents.

Purpose of the Study:

• To review recent advancements in FBDD for discovering Mycobacterium tuberculosis inhibitors.
• To highlight progress in various therapeutic pathways targeting TB.
• To discuss hit discovery, hit-to-lead optimization, SAR, and binding modes.

Main Methods:

• Literature review of fragment-based approaches in anti-TB drug discovery.
• Analysis of FBDD strategies including fragment growing, merging, and linking.
• Examination of structure-activity relationships (SAR) and binding modes of identified inhibitors.

Main Results:

• Fragment-based approaches have shown significant progress in identifying novel TB inhibitors.
• Various pathways are being explored for TB treatment using FBDD.
• Successful examples of hit-to-lead optimization and SAR studies are presented.

Conclusions:

• FBDD is a powerful methodology for developing new classes of anti-tuberculosis drugs.
• Continued application of FBDD is vital to address the challenge of drug-resistant TB.
• This review provides insights into the current landscape and future directions of FBDD for TB.