New anti-tuberculosis agents amongst known drugs.
Mycobacterium tuberculosis has an on-going impact on global public health and new therapeutics to treat tuberculosis are urgently required. The emergence of drug resistant tuberculosis poses a serious threat to the control of this pathogen, and the development of drugs that are active against the resistant strains is vital. A medium-throughput assay using the Alamar Blue reagent was set-up to identify novel inhibitors of M. tuberculosis from a library of known drugs, for which there has already been extensive research investigating their suitability and safety as human therapeutics. Of the 1514 compounds screened, 53 were demonstrated to possess inhibitory properties against M. tuberculosis at a concentration of 5microM or below. Of these, 17 were novel inhibitors while 36 were known tuberculosis drugs or had been previously described as possessing anti-tuberculosis activity. Five compounds were selected as those which represent the most promising starting points for new anti-tuberculosis agents. It was demonstrated that all five were active against intracellular M. tuberculosis in a macrophage model of infection. The anti-tuberculosis agents identified in this screen represent promising new scaffolds on which future drug development efforts can be focused.
Lougheed
Kathryn E A
KE
Division of Mycobacterial Research, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom. kloughe@nimr.mrc.ac.uk
Taylor
Debra L
DL
Osborne
Simon A
SA
Bryans
Justin S
JS
Buxton
Roger S
RS
D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000187:drug effects* / Q000235:genetics; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D054852:Small Molecule Libraries; D014376:Tuberculosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D054852:Small Molecule Libraries
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