Abstract
New amino acids 7-12 were designed and synthesized as candidate inhibitors of human nitric oxide synthase (NOS). The 2-aminopyridine-containing l-amino acids 8 had potent inhibitory activity toward all of the human NOS isozymes. However, the regioisomers 9 and 10, and 2-methylpyridine-containing compound 11 had much lower inhibitory activity. Human NOS isozymes were also inhibited by 7, which lacks an amino group on the pyridine moiety. A computational docking study was carried out to investigate the mechanism of the inhibitory effect.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acids / chemical synthesis
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Amino Acids / chemistry*
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Amino Acids / pharmacology*
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Animals
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Cell Line
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Computer Simulation
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Drug Design*
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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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Humans
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / genetics
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Models, Molecular
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Molecular Structure
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Nitric Oxide Synthase / antagonists & inhibitors*
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Protein Conformation
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Pyridines / chemistry*
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Pyridines / pharmacology*
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / genetics
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Structure-Activity Relationship
Substances
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Amino Acids
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Enzyme Inhibitors
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Isoenzymes
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Pyridines
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Recombinant Proteins
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Nitric Oxide Synthase