Document
ethambutol, 10054-05-4, 1070-11-7, 3577-94-4, 74-55-5; isoniazid, 54-85-3, 62229-51-0, 65979-32-0; mutase, 9047-56-7; quinine, 130-89-2, 130-95-0, 14358-44-2, 549-48-4, 549-49-5, 60-93-5, 7549-43-1; rifampicin, 13292-46-1; uridine diphosphate, 58-98-0; (4-chlorophenyl)-(1-(4-chlorophenyl)-3-hydroxy-5-methyl-1H-pyrazol-4-yl)methanone; 3-(4-iodophenyl)-2-(4-(3,4-dichlorophenyl)thiazol-2-ylamino)propionic acid; Anti-Bacterial Agents; Antitubercular Agents; Enzyme Inhibitors; Intramolecular Transferases, 5.4.-; Phenylalanine, 63-91-2; Pyrazoles; Thiazoles; UDP-galactopyranose mutase, 5.4.99.9
Mycobacteria; Tuberculosis; UDP-galactopyranose mutase inhibitors (4 chlorophenyl) [1 (4 chlorophenyl) 3 hydroxy 5 methyl 1h pyrazol 4 yl]methadone; 3 (4 iodophenyl) 2 [4 (3,4 dichlorophenyl)thiazol 2 ylamino]propionic acid; antimycobacterial agent; ethambutol; isoniazid; mutase; quinine; rifampicin; unclassified drug; uridine diphosphate; uridine diphosphate galactopyranose mutase; uridine diphosphate galactopyranose mutase inhibitor; antimicrobial activity; article; bacterial strain; controlled study; drug cytotoxicity; drug potency; drug synthesis; human; human cell; Klebsiella pneumoniae; macrophage; minimum inhibitory concentration; mycobacteriosis; Mycobacterium; Mycobacterium bovis; Mycobacterium smegmatis; Mycobacterium tuberculosis; nonhuman; priority journal; protein targeting; Anti-Bacterial Agents; Antitubercular Agents; Cell Line; Enzyme Inhibitors; Humans; Intramolecular Transferases; Macrophages; Microbial Sensitivity Tests; Models, Molecular; Mycobacterium; Mycobacterium bovis; Mycobacterium tuberculosis; Phenylalanine; Pyrazoles; Thiazoles
The galactofuran region of the mycobacterial cell wall consists of alternating 5- and 6-linked β-d-galactofuranose (β-d-Gal. f) residues, essential for viability. UDP-galactofuranose (UDP-Gal. f), the donor for Gal. f, is synthesised from UDP-galactopyranose (UDP-Gal. p) by the enzyme UDP-galactopyranose mutase (UGM), which is not found in humans, rendering it a therapeutic target. The in vitro properties, i.e. enzymatic activity, antimycobacterial activity, cellular toxicity, activity in mycobacterial-infected macrophages and activity against non-replicating persistent mycobacteria, of (4-chlorophenyl)-[1-(4-chlorophenyl)-3-hydroxy-5-methyl-1H-pyrazol-4-yl]-methanone and 3-(4-iodophenyl)-2-[4-(3,4-dichlorophenyl)-thiazol-2-ylamino]-propionic acid were studied. The former compound, a pyrazole, was an inhibitor of UGM from Mycobacterium tuberculosis and Klebsiella pneumoniae and was effective against Mycobacterium smegmatis, Mycobacterium bovis BCG and M. tuberculosis but ineffective against other bacterial strains tested. This compound showed potency against mycobacteria in infected macrophages but exhibited moderate cellular toxicity and was ineffective against non-replicating persistent mycobacteria. This is the first report of a compound both with UGM inhibitory properties and broad antimycobacterial activities. The latter compound, an aminothiazole, was active against UGM from K. pneumoniae and M. tuberculosis but was ineffective against M. bovis BCG or M. tuberculosis as well as demonstrating higher cellular toxicity. These data validate the choice of UGM as a target for active antimycobacterial therapy and confirm the pyrazole compound as a viable lead candidate. © 2010 Elsevier B.V. and the International Society of Chemotherapy.
Antimycobacterial activity of UDP-galactopyranose mutase inhibitors
Generically Dependent Continuant
RDF description of Antimycobacterial activity of UDP-galactopyranose mutase inhibitors - http://orbis.uaslp.mx/vivo/individual/scopus2463
International Journal of Antimicrobial Agents
Article
Information Content Entity
Natural Sciences and Engineering Research Council of Canada, NSERC