Fragment-based approaches to TB drugs.
Tuberculosis is an infectious disease associated with significant mortality and morbidity worldwide, particularly in developing countries. The rise of antibiotic resistance in Mycobacterium tuberculosis (Mtb) urgently demands the development of new drug leads to tackle resistant strains. Fragment-based methods have recently emerged at the forefront of pharmaceutical development as a means to generate more effective lead structures, via the identification of fragment molecules that form weak but high quality interactions with the target biomolecule and subsequent fragment optimization. This review highlights a number of novel inhibitors of Mtb targets that have been developed through fragment-based approaches in recent years.
Department of Chemistry,University of Cambridge,Lensfield Road,Cambridge CB2 1EW,UK.
Chiara
C
Marchetti
Department of Chemistry,University of Cambridge,Lensfield Road,Cambridge CB2 1EW,UK.
Daniel S H
DSH
Chan
Department of Chemistry,University of Cambridge,Lensfield Road,Cambridge CB2 1EW,UK.
Anthony G
AG
Coyne
Department of Chemistry,University of Cambridge,Lensfield Road,Cambridge CB2 1EW,UK.
Chris
C
Abell
D001426:Bacterial Proteins / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010453:Peptide Synthases / Q000037:antagonists & inhibitors / Q000187:drug effects; D012097:Repressor Proteins / Q000187:drug effects; D000637:Transaminases / Q000187:drug effects; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
D001426:Bacterial Proteins; C481661:EthR protein, Mycobacterium tuberculosis; D012097:Repressor Proteins; D003577:Cytochrome P-450 Enzyme System; D000637:Transaminases; C102100:BioA protein, bacteria; D010453:Peptide Synthases; C022318:pantothenate synthetase
BioA; EthR; cytochrome P450; fragment-based approaches; medicinal chemistry; pantothenate synthetase; tuberculosis