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.
|Autori:||Granchi C; Roy S; Mottinelli M; Nardini E; Campinoti F; Tuccinardi T; Lanza M; Betti L; Giannaccini G; Lucacchini A; Martinelli A; Macchia M; Minutolo F|
|Titolo:||Synthesis of sulfonamide-containing N-hydroxyindole-2-carboxylates as inhibitors of human lactate dehydrogenase-isoform 5|
|Anno del prodotto:||2011|
|Digital Object Identifier (DOI):||10.1016/j.bmcl.2011.10.031|
|Appare nelle tipologie:||1.1 Articolo in rivista|