Journal
ORGANIC & BIOMOLECULAR CHEMISTRY
Volume 11, Issue 38, Pages 6588-6596Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3ob40870a
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Funding
- NIH [R01GM098453]
- University of Pisa
- University of Illinois
- NIH Ruth L. Kirschstein National Research Service Award [1F30CA168323-01]
- National Science Foundation, Division of Biological Infrastructure [DBI-0100085]
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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.
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