Abstract
Analogues of the natural antibiotic thiolactomycin, with acetylene-based side chains, have the highest recorded in vitro inhibitory activity against the recombinant Mycobacterium tuberculosis beta-ketoacyl-ACP synthase mtFabH condensing enzyme. In particular, 5-[3-(4-acetyl-phenyl)-prop-2-ynyl]-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one exhibited more than an 18-fold increased potency, compared to thiolactomycin, against this key condensing enzyme, involved in M. tuberculosis mycolic acid biosynthesis. Analogues of the antibiotic thiolactomycin, with acetylene-based side chains, have the highest recorded activity against cloned mtFabH condensing enzyme.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylene / analogs & derivatives*
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Acetylene / pharmacology
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Acetyltransferases / antagonists & inhibitors
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Acetyltransferases / metabolism
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Bacterial Proteins / antagonists & inhibitors
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Bacterial Proteins / metabolism
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Fatty Acid Synthase, Type II
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Fatty Acid Synthases / antagonists & inhibitors
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Fatty Acid Synthases / metabolism
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Multienzyme Complexes / antagonists & inhibitors
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Multienzyme Complexes / metabolism
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Mycobacterium tuberculosis / drug effects*
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Mycobacterium tuberculosis / enzymology*
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Thiophenes / chemistry*
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Thiophenes / pharmacology
Substances
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Bacterial Proteins
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Enzyme Inhibitors
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Multienzyme Complexes
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Thiophenes
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thiolactomycin
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Acetyltransferases
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Fatty Acid Synthases
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Fatty Acid Synthase, Type II
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fatty acid synthase I, mycobacteria
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Acetylene