Abstract
A series of pyridine-2-carboxylic acid derivatives were synthesized according to the leads from the screening, and potent inhibitors have been obtained by structural modification. They have shown submicromolar inhibition of the enzymes (for example, for 9n, IC(50) = 130 nM for EcMetAP1 and IC(50) = 380 nM for ScMetAP1). They represent small-molecule MetAP inhibitors with novel structures different from alkylating fumagillin derivatives and peptidic bestatin-based MetAP inhibitor.
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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Aminopeptidases / antagonists & inhibitors*
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Anti-Bacterial Agents
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Anti-Infective Agents / chemical synthesis*
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Anti-Infective Agents / chemistry
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Anti-Infective Agents / pharmacology
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Binding Sites
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Crystallography, X-Ray
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Escherichia coli / enzymology*
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Methionyl Aminopeptidases
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Models, Molecular
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Protein Binding
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacology
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Saccharomyces cerevisiae / enzymology*
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / chemistry
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Thiazoles / pharmacology
Substances
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Anti-Bacterial Agents
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Anti-Infective Agents
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Enzyme Inhibitors
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Pyridines
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Thiazoles
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Aminopeptidases
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Methionyl Aminopeptidases