Dual Targeting of the Warburg Effect with a Glucose-Conjugated Lactate Dehydrogenase Inhibitor

Effective glucose diet: We report the development and activity of glucose-conjugated LDH-A inhibitors designed for dual targeting of the Warburg effect (elevated glucose uptake and glycolysis) in cancer cells. Glycoconjugation could be applied to inhibitors of many enzymes involved in glycolysis or tumor metabolism

Chemical Science MINIREVIEW View Article Online

Glucose conjugation for the specific targeting and treatment of cance

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

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 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

AGENTI TERAPEUTICI IN GRADO DI RIDURRE LA PRODUZIONE CELLULARE DI ACIDO LATTICO E COMPOSIZIONI FARMACEUTICHE CHE COMPRENDONO TALI COMPOSTI

La presente invenzione riguarda composti in grado di inibire la produzione di lattato (acido lattico) coinvolta nell’angiogenesi dei tessuti cancerosi, nonché nel processo metabolico glicolitico delle cellule tumorali, delle cellule del sistema immunitario in patologie asmatiche, delle cellule vascolari nell’ipertensione polmonare, e nel processo attraverso il quale i protozoi parassiti che provocano la malaria ottengono la maggior parte dell’energia loro necessaria