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

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

  • Org Biomol Chem. 2013 Oct 14;11(38):6588-96. doi: 10.1039/c3ob40870a.
Carlotta Granchi 1 Emilia C Calvaresi Tiziano Tuccinardi Ilaria Paterni Marco Macchia Adriano Martinelli Paul J Hergenrother Filippo Minutolo
Affiliations

Affiliation

  • 1 Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, I-56126 Pisa, Italy. filippo.minutolo@farm.unipi.it.
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.

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