title: Synthesis of sulfonamide-containing N-hydroxyindole-2-carboxylates as inhibitors of human lactate dehydrogenase-isoform 5.
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 K(i) 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 (K(i) values as low as 5.6 μM) and behaved as competitive inhibitors versus both the substrate and the cofactor.
authors: Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors: Carlotta
authors: C
authors: Granchi
authors: Sarabindu
authors: S
authors: Roy
authors: Marco
authors: M
authors: Mottinelli
authors: Elisa
authors: E
authors: Nardini
authors: Fabio
authors: F
authors: Campinoti
authors: Tiziano
authors: T
authors: Tuccinardi
authors: Mario
authors: M
authors: Lanza
authors: Laura
authors: L
authors: Betti
authors: Gino
authors: G
authors: Giannaccini
authors: Antonio
authors: A
authors: Lucacchini
authors: Adriano
authors: A
authors: Martinelli
authors: Marco
authors: M
authors: Macchia
authors: Filippo
authors: F
authors: Minutolo
mesh_terms: D001665:Binding Sites; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D017434:Protein Structure, Tertiary; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D013449:Sulfonamides; C030374:indole; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C409667:lactate dehydrogenase 1