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Oxamic acid analogues as LDH-C4-specific competitive inhibitors

2011; Taylor & Francis; Volume: 26; Issue: 4 Linguagem: Inglês

10.3109/14756366.2011.566221

1475-6374

Lorena Rodríguez‐Páez, Miguel Angel Chena-Taboada, Arturo Cabrera-Hernández, Joaquin Cordero‐Martínez, Carlos Wong,

Aldose Reductase and Taurine

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.