Recent advances in Fragment-based strategies against tuberculosis

Abstract

Tuberculosis remains one of the world's leading infectious disease killers, causing more than 1.5 million of deaths each year. It is therefore a priority to discover and develop new classes of anti-tuberculosis drugs to design new treatments in order to fight the increasing burden of resistant-tuberculosis. Fragment-based drug discovery (FBDD) relies on the identification of small molecule hits, further improved to high-affinity ligands through three main approaches: fragment growing, merging and linking. The aim of this review is to highlight the recent progresses made in fragment-based approaches for the discovery and development of Mycobacterium tuberculosis inhibitors in a wide range of pathways. Hit discovery, hit-to-lead optimization, SAR and binding mode when available are discussed.

Keywords: Fragment-based drug design; Fragments; Review; Tuberculosis.