| Autor: |
Manos-Turvey A; School of Chemistry, Building F11, The University of Sydney, Camperdown, NSW 2006, Australia., Cergol KM, Salam NK, Bulloch EM, Chi G, Pang A, Britton WJ, West NP, Baker EN, Lott JS, Payne RJ |
| Jazyk: |
angličtina |
| Zdroj: |
Organic & biomolecular chemistry [Org Biomol Chem] 2012 Dec 14; Vol. 10 (46), pp. 9223-36. Date of Electronic Publication: 2012 Oct 29. |
| DOI: |
10.1039/c2ob26736e |
| Abstrakt: |
Mycobacterium tuberculosis salicylate synthase (MbtI) catalyses the first committed step in the biosynthesis of mycobactin T, an iron-chelating siderophore essential for the virulence and survival of M. tuberculosis. Co-crystal structures of MbtI with members of a first generation inhibitor library revealed large inhibitor-induced rearrangements within the active site of the enzyme. This plasticity of the MbtI active site was probed via the preparation of a library of inhibitors based on a 2,3-dihydroxybenzoate scaffold with a range of substituted phenylacrylate side chains appended to the C3 position. Most compounds exhibited moderate inhibitory activity against the enzyme, with inhibition constants in the micromolar range, while several dimethyl ester variants possessed promising anti-tubercular activity in vitro. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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