Abstract
A head-to-head study of representative examples of N-hydroxyindole-2-carboxylates (NHI) and malonic derivatives (Mal) as LDH-A inhibitors was conducted, comparing the enzyme inhibition potency, cellular uptake, reduction of lactate production in cancer cells and anti-proliferative activity. Among the compounds tested, methyl 1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indole-2-carboxylate (2, NHI-2), a methyl ester belonging to the NHI class, displayed optimal properties in the cell-based assays, proving to be an efficient anti-glycolytic agent against cancer cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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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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HeLa Cells
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Humans
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Indoles / chemical synthesis
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Indoles / chemistry
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Indoles / pharmacology*
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism
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L-Lactate Dehydrogenase / antagonists & inhibitors*
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L-Lactate Dehydrogenase / metabolism
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Lactate Dehydrogenase 5
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Lactic Acid / antagonists & inhibitors
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Lactic Acid / biosynthesis
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Malonates / chemical synthesis
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Malonates / chemistry
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Malonates / pharmacology*
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Models, Molecular
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Molecular Structure
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Indoles
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Isoenzymes
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Malonates
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methyl 1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indole-2-carboxylate
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Lactic Acid
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L-Lactate Dehydrogenase
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Lactate Dehydrogenase 5