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.
Bioorganic & medicinal chemistry letters 10/2011; 21(24):7331-6. · 2.65 Impact Factor