title: Oxamic acid analogues as LDH-C4-specific competitive inhibitors.
abstract: We performed kinetic studies to determine whether oxamate analogues are selective inhibitors of LDH-C4, owing to their potential usefulness in fertility control and treatment of some cancers. These substances were shown to be competitive inhibitors of LDH isozymes and are able to discriminate among subtle differences that differentiate the active sites of LDH-A4, LDH-B4 and LDH-C4. N-Ethyl oxamate was the most potent inhibitor showing the highest affinity for LDH-C4. However, N-propyl oxamate was the most selective inhibitor showing a high degree of selectivity towards LDH-C4. Non-polar four carbon atoms chains, linear or branched, dramatically diminished the affinity and selectivity towards LDH-C4. N-Propyl oxamate significantly reduced ATP levels, capacitation and mouse sperm motility, in line with results shown by others, suggesting that LDH-C4 plays an essential role in mouse fertility.
authors: Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Prol. Carpio y Plan de Ayala, México, D.F. México. lrodrig@encb.ipn.mx
authors: Lorena
authors: L
authors: Rodríguez-Páez
authors: Miguel Angel
authors: MA
authors: Chena-Taboada
authors: Arturo
authors: A
authors: Cabrera-Hernández
authors: Joaquín
authors: J
authors: Cordero-Martínez
authors: Carlos
authors: C
authors: Wong
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013737:Testis / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; C409673:lactate dehydrogenase C4; D010072:Oxamic Acid