TY - JOUR
T1 - Oxamic acid analogues as LDH-C4-specific competitive inhibitors
AU - Rodríguez-Páez, Lorena
AU - Chena-Taboada, Miguel Angel
AU - Cabrera-Hernández, Arturo
AU - Cordero-Martínez, Joaquín
AU - Wong, Carlos
N1 - Funding Information:
This work was partially supported by research grants from the Secretaría de Investigación y Posgrado del Instituto Politécnico Nacional (SIP-IPN), México. C.W. and L.R.P. are fellows of the COFAA-IPN and of the SNI-CONACYT. M.A.Ch.T., A.C.H. and J.C.M. were fellows of the CONACYT and PIFI-IPN.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - Inhibitors LDH isozymes
KW - LDH-C4 inhibition
KW - Oxamate derivatives
UR - http://www.scopus.com/inward/record.url?scp=79959903969&partnerID=8YFLogxK
U2 - 10.3109/14756366.2011.566221
DO - 10.3109/14756366.2011.566221
M3 - Artículo
C2 - 21438710
SN - 1475-6366
VL - 26
SP - 579
EP - 586
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 4
ER -