N-Hydroxyindole-2-carboxylates possessing sulfonamide-substituents at either position 5 or 6 were designed and synthesized. The inhibitory activities of these compounds against isoforms 1 and 5 of human lactate dehydrogenase were analysed, and Ki values of the most efficient inhibitors were determined by standard enzyme kinetic studies. Some of these compounds displayed state-of-the-art inhibitory potencies against isoform 5 (Ki values as low as 5.6 μM) and behaved as competitive inhibitors versus both the substrate and the cofactor.

Synthesis of sulfonamide-containing N-hydroxyindole-2-carboxylates as inhibitors of human lactate dehydrogenase-isoform 5

GRANCHI, CARLOTTA;TUCCINARDI, TIZIANO;BETTI, LAURA;GIANNACCINI, GINO;LUCACCHINI, ANTONIO;MARTINELLI, ADRIANO;MACCHIA, MARCO;MINUTOLO, FILIPPO
2011

Abstract

N-Hydroxyindole-2-carboxylates possessing sulfonamide-substituents at either position 5 or 6 were designed and synthesized. The inhibitory activities of these compounds against isoforms 1 and 5 of human lactate dehydrogenase were analysed, and Ki values of the most efficient inhibitors were determined by standard enzyme kinetic studies. Some of these compounds displayed state-of-the-art inhibitory potencies against isoform 5 (Ki values as low as 5.6 μM) and behaved as competitive inhibitors versus both the substrate and the cofactor.
Granchi, Carlotta; Roy, S; Mottinelli, M; Nardini, E; Campinoti, F; Tuccinardi, Tiziano; Lanza, M; Betti, Laura; Giannaccini, Gino; Lucacchini, Antonio; Martinelli, Adriano; Macchia, Marco; Minutolo, Filippo
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/189004
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