Abstract
Analogues of the antibiotic thiolactomycin, with biphenyl-based 5-substituents, were found to have excellent in vitro inhibitory activity against the recombinant Mycobacterium tuberculosis beta-ketoacyl-ACP synthase mtFabH condensing enzyme. In particular, 5-(4'-benzyloxy-biphen-4-ylmethyl)-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one exhibited approximately a 4-fold increased potency against this key condensing enzyme involved in M. tuberculosis mycolic acid biosynthesis, compared to thiolactomycin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / antagonists & inhibitors*
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3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / metabolism
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Acetyltransferases / antagonists & inhibitors
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Alkylation
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Anti-Bacterial Agents / pharmacology*
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Fatty Acid Synthase, Type II
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Fatty Acid Synthases / antagonists & inhibitors
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Multienzyme Complexes / antagonists & inhibitors
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Mycobacterium tuberculosis / drug effects*
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Mycobacterium tuberculosis / metabolism
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Mycolic Acids / metabolism
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Recombinant Proteins / metabolism
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Thiophenes / pharmacology*
Substances
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Anti-Bacterial Agents
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Multienzyme Complexes
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Mycolic Acids
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Recombinant Proteins
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Thiophenes
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thiolactomycin
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Acetyltransferases
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3-Oxoacyl-(Acyl-Carrier-Protein) Synthase
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Fatty Acid Synthases
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Fatty Acid Synthase, Type II