Assessing the differential action on cancer cells of LDH-A inhibitors based on the N-hydroxyindole-2-carboxylate (NHI) and malonic (Mal) scaffolds

Carlotta Granchi, Emilia C. Calvaresi, Tiziano Tuccinardi, Ilaria Paterni, Marco Macchia, Adriano Martinelli, Paul J. Hergenrother, Filippo Minutolo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)6588-6596
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume11
Issue number38
DOIs
StatePublished - Oct 14 2013

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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