Lactate Dehydrogenase Inhibition: Biochemical Relevance and Therapeutical Potential

Author(s): Giuseppina Laganá , Davide Barreca* , Antonella Calderaro , Ersilia Bellocco .

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 18 , 2019

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Abstract:

Lactate dehydrogenase (LHD) is a key enzyme of anaerobic metabolism in almost all living organisms and it is also a functional checkpoint for glucose restoration during gluconeogenesis and single-stranded DNA metabolism. This enzyme has a well preserved structure during evolution and among the species, with little, but sometimes very useful, changes in the amino acid sequence, which makes it an attractive target for the design and construction of functional molecules able to modulate its catalytic potential and expression. Research has focused mainly on the selection of modulator especially as far as LDH isozymes (especially LDH-5) and lactate dehydrogenases of Plasmodium falciparum (pfLDH) are concerned. This review summarizes the recent advances in the design and development of inhibitors, pointing out their specificity and therapeutic potentials.

Keywords: Lactate dehydrogenase, enzyme inhibitors, quinoline derivatives, oxamate and derivatives, galloflavin, bifunctional inhibitors, miRNA and shRNAs.

[1]
White, J.L.; Hackert, M.L.; Buehner, M.; Adams, M.J.; Ford, G.C.; Lentz, P.J., Jr; Smiley, I.E.; Steindel, S.J.; Rossmann, M.G. A comparison of the structures of apo dogfish M4 lactate dehydrogenase and its ternary complexes. J. Mol. Biol., 1976, 102(4), 759-779.
[http://dx.doi.org/10.1016/0022-2836(76)90290-4] [PMID: 940154]
[2]
Grau, U.M.; Trommer, W.E.; Rossmann, M.G. Structure of the active ternary complex of pig heart lactate dehydrogenase with S-lac-NAD at 2.7 A resolution. J. Mol. Biol., 1981, 151(2), 289-307.
[http://dx.doi.org/10.1016/0022-2836(81)90516-7] [PMID: 7338899]
[3]
Piontek, K.; Chakrabarti, P.; Schär, H.P.; Rossmann, M.G.; Zuber, H. Structure determination and refinement of Bacillus stearothermophilus lactate dehydrogenase. Proteins, 1990, 7(1), 74-92.
[http://dx.doi.org/10.1002/prot.340070108] [PMID: 2330370]
[4]
Iwata, S.; Ohta, T. Molecular basis of allosteric activation of bacterial L-lactate dehydrogenase. J. Mol. Biol., 1993, 230(1), 21-27.
[http://dx.doi.org/10.1006/jmbi.1993.1122] [PMID: 8450537]
[5]
Dunn, C.R.; Banfield, M.J.; Barker, J.J.; Higham, C.W.; Moreton, K.M.; Turgut-Balik, D.; Brady, R.L.; Holbrook, J.J. The structure of lactate dehydrogenase from Plasmodium falciparum reveals a new target for anti-malarial design. Nat. Struct. Biol., 1996, 3(11), 912-915.
[http://dx.doi.org/10.1038/nsb1196-912] [PMID: 8901865]
[6]
Read, J.A.; Winter, V.J.; Eszes, C.M.; Sessions, R.B.; Brady, R.L. Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase. Proteins, 2001, 43(2), 175-185.
[http://dx.doi.org/10.1002/1097-0134(20010501)43:2<175:AID-PROT1029>3.0.CO;2-#] [PMID: 11276087]
[7]
Kolappan, S.; Shen, D.L.; Mosi, R.; Sun, J.; McEachern, E.J.; Vocadlo, D.J.; Craig, L. Structures of lactate dehydrogenase A (LDHA) in apo, ternary and inhibitor-bound forms. Acta Crystallogr. D Biol. Crystallogr., 2015, 71, 185-195. Swiderek, K.; Paneth, P. Differences and similarities in binding of pyruvate and L-lactate in the active site of M4 and H4 isoforms of human lactate dehydrogenase. Arch. Biochem. Biophys., 2011, 505, 33-41.
[http://dx.doi.org/10.1016/j.abb.2010.10.010]
[8]
Swiderek, K.; Paneth, P. Differences and similarities in binding of pyruvate and L-lactate in the active site of M4 and H4 isoforms of human lactate dehydrogenase. Arch. Biochem. Biophys., 2011, 505, 33-41.
[http://dx.doi.org/10.1016/j.abb.2010.10.010]
[9]
Quistorff, B.; Grunnet, N. The isoenzyme pattern of LDH does not play a physiological role; except perhaps during fast transitions in energy metabolism. Aging (Albany NY), 2011, 3(5), 457-460.
[http://dx.doi.org/10.18632/aging.100329] [PMID: 21566263]
[10]
He, H.; Lee, M.C.; Zheng, L.L.; Zheng, L.; Luo, Y. Integration of the metabolic/redox state, histone gene switching, DNA replication and S-phase progression by moonlighting metabolic enzymes. Biosci. Rep., 2013, 33(2)e00018
[http://dx.doi.org/10.1042/BSR20120059] [PMID: 23134369]
[11]
Dai, R.P.; Yu, F.X.; Goh, S.R.; Chng, H.W.; Tan, Y.L.; Fu, J.L.; Zheng, L.; Luo, Y. Histone 2B (H2B) expression is confined to a proper NAD+/NADH redox status. J. Biol. Chem., 2008, 283(40), 26894-26901.
[http://dx.doi.org/10.1074/jbc.M804307200] [PMID: 18682386]
[12]
Wang, X.C.; Jiang, L.; Zhou, H.M. Minimal functional unit of lactate dehydrogenase. J. Protein Chem., 1997, 16(3), 227-231.
[http://dx.doi.org/10.1023/A:1026382926299] [PMID: 9155093]
[13]
Wang, Z.Y.; Loo, T.Y.; Shen, J.G.; Wang, N.; Wang, D.M.; Yang, D.P.; Mo, S.L.; Guan, X.Y.; Chen, J.P. LDH-A silencing suppresses breast cancer tumorigenicity through induction of oxidative stress mediated mitochondrial pathway apoptosis. Breast Cancer Res. Treat., 2012, 131(3), 791-800.
[http://dx.doi.org/10.1007/s10549-011-1466-6] [PMID: 21452021]
[14]
Rong, Y.; Wu, W.; Ni, X.; Kuang, T.; Jin, D.; Wang, D.; Lou, W. Lactate dehydrogenase A is overexpressed in pancreatic cancer and promotes the growth of pancreatic cancer cells. Tumour Biol., 2013, 34(3), 1523-1530.
[http://dx.doi.org/10.1007/s13277-013-0679-1] [PMID: 23404405]
[15]
Fan, J.; Hitosugi, T.; Chung, T.W.; Xie, J.; Ge, Q.; Gu, T.L.; Polakiewicz, R.D.; Chen, G.Z.; Boggon, T.J.; Lonial, S.; Khuri, F.R.; Kang, S.; Chen, J. Tyrosine phosphorylation of lactate dehydrogenase A is important for NADH/NAD(+) redox homeostasis in cancer cells. Mol. Cell. Biol., 2011, 31(24), 4938-4950.
[http://dx.doi.org/10.1128/MCB.06120-11] [PMID: 21969607]
[16]
Baker, B.R.; Bramhall, R.R. Irreversible enzyme inhibitors. 189. Inhibition of some dehydrogenases by derivatives of 4-hydroxyquinoline-2 and -3-carboxylic acids. J. Med. Chem., 1972, 15(3), 230-233.
[http://dx.doi.org/10.1021/jm00273a005] [PMID: 5059206]
[17]
Baker, B.R.; Bramhall, R.R. Irreversible enzyme inhibitors. 190. Inhibition of some dehydrogenases by l-substituted-1,4-dihydro-4-quinoline-3-carboxylic acids. J. Med. Chem., 1972, 15(3), 233-235.
[http://dx.doi.org/10.1021/jm00273a006] [PMID: 5059207]
[18]
Baker, B.R.; Bramhall, R.R. Irreversible enzyme inhibitors. 191. Hydrophobic bonding to some dehydrogenases by 6-, 7-, or 8-substituted-4-hydroxyquinoline-3-carboxylic acids. J. Med. Chem., 1972, 15(3), 235-237.
[http://dx.doi.org/10.1021/jm00273a007] [PMID: 5059208]
[19]
Baker, B.R.; Bramhall, R.R. Irreversible enzyme inhibitors. 192. Hydrophobic bonding to some dehydrogenases with 5-substituted-4-hydroxyquinoline-3-carboxylic acids. J. Med. Chem., 1972, 15(3), 237-241.
[http://dx.doi.org/10.1021/jm00273a008] [PMID: 5062068]
[20]
Billiard, J.; Annan, R.; Ariazi, J. Rapid LDH5 inhibition reverses malignant metabolic phenotype and impairs survival of hepatocellular carcinoma cells. Cancer Res, 2013, 73(8 Suppl) Abstract nr 5418.
[http://dx.doi.org/10.1158/1538-7445.AM2013-5418]
[21]
Chai, D.; Colon, M.; Dodson, C.; Duffy, K. J. Chemical compounds. GlaxoSmithKline Llc, 2012.patent number: WO/2013/096153.
[22]
Cortopassi, W.A.; Oliveira, A.A.; Guimarães, A.P.; Rennó, M.N.; Krettli, A.U.; França, T.C.C. Docking Studies on the binding of quinoline derivatives and hematin to lactate dehydrogenase. J. Biomol. Struct. Dyn., 2011, 29, 207-218.
[http://dx.doi.org/10.1080/07391102.2011.10507383] [PMID: 21696234]
[23]
Akagawa, M.; Minematsu, K.; Shibata, T.; Kondo, T.; Ishii, T.; Uchida, K. Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein. Sci. Rep., 2016, 6, 26723.
[http://dx.doi.org/10.1038/srep26723] [PMID: 27230956]
[24]
Manerba, M.; Vettraino, M.; Fiume, L.; Di Stefano, G.; Sartini, A.; Giacomini, E.; Buonfiglio, R.; Roberti, M.; Recanatini, M. Galloflavin (CAS 568–580–589): A novel inhibitor of lactate dehydrogenase. ChemMedChem, 2012, 7(2), 311-317.
[http://dx.doi.org/10.1002/cmdc.201100471] [PMID: 22052811]
[25]
Farabegoli, F.; Vettraino, M.; Manerba, M.; Fiume, L.; Roberti, M.; Di Stefano, G. Galloflavin, a new lactate dehydrogenase inhibitor, induces the death of human breast cancer cells with different glycolytic attitude by affecting distinct signaling pathways. Eur. J. Pharm. Sci., 2012, 47(4), 729-738.
[http://dx.doi.org/10.1016/j.ejps.2012.08.012] [PMID: 22954722]
[26]
Fiume, L.; Vettraino, M.; Carnicelli, D.; Arfilli, V.; Di Stefano, G.; Brigotti, M. Galloflavin prevents the binding of lactate dehydrogenase A to single stranded DNA and inhibits RNA synthesis in cultured cells. Biochem. Biophys. Res. Commun., 2013, 430(2), 466-469.
[http://dx.doi.org/10.1016/j.bbrc.2012.12.013] [PMID: 23237800]
[27]
Choi, S.R.; Beeler, A.B.; Pradhan, A.; Watkins, E.B.; Rimoldi, J.M.; Tekwani, B.; Avery, M.A. Generation of oxamic acid libraries: antimalarials and inhibitors of Plasmodium falciparum lactate dehydrogenase. J. Comb. Chem., 2007, 9(2), 292-300.
[http://dx.doi.org/10.1021/cc060110n] [PMID: 17316052]
[28]
Moreno-Sánchez, R.; Marín-Hernández, Á.; Del Mazo-Monsalvo, I.; Saavedra, E.; Rodríguez-Enríquez, S. Assessment of the low inhibitory specificity of oxamate, aminooxyacetate and dichloroacetate on cancer energy metabolism. Biochim. Biophys. Acta Gen. Subj, 2017, 1861(1ptA). , 3221-3236.
[http://dx.doi.org/10.1016/j.bbagen.2016.08.006]
[29]
Wong, C.; Rodríguez-Páez, L.; Nogueda, B.; Pérez, A.; Baeza, I. Selective inhibition of the sperm-specific lactate dehydrogenase isozyme-C4 by N-isopropyl oxamate. Biochim. Biophys. Acta, 1997, 1343(1), 16-22.
[http://dx.doi.org/10.1016/S0167-4838(97)00090-3] [PMID: 9428654]
[30]
Koslowski, M.; Türeci, O.; Bell, C.; Krause, P.; Lehr, H.A.; Brunner, J.; Seitz, G.; Nestle, F.O.; Huber, C.; Sahin, U. Multiple splice variants of lactate dehydrogenase C selectively expressed in human cancer. Cancer Res., 2002, 62(22), 6750-6755.
[PMID: 12438276]
[31]
Rodríguez-Páez, L.; Chena-Taboada, M.A.; Cabrera-Hernández, A.; Cordero-Martínez, J.; Wong, C. Oxamic acid analogues as LDH-C4-specific competitive inhibitors. J. Enzyme Inhib. Med. Chem., 2011, 26(4), 579-586.
[http://dx.doi.org/10.3109/14756366.2011.566221] [PMID: 21438710]
[32]
Kotlyar, A.B.; Randazzo, A.; Honbo, N.; Jin, Z.Q.; Karliner, J.S.; Cecchini, G. Cardioprotective activity of a novel and potent competitive inhibitor of lactate dehydrogenase. FEBS Lett., 2010, 584(1), 159-165.
[http://dx.doi.org/10.1016/j.febslet.2009.11.022] [PMID: 19913538]
[33]
Dodou, K.; Anderson, R.J.; Small, D.A.; Groundwater, P.W. Investigations on gossypol: past and present developments. Expert Opin. Investig. Drugs, 2005, 14(11), 1419-1434.
[http://dx.doi.org/10.1517/13543784.14.11.1419] [PMID: 16255680]
[34]
Shelley, M.D.; Hartley, L.; Fish, R.G.; Groundwater, P.; Morgan, J.J.G.; Mort, D.; Mason, M.; Evans, A. Stereo-specific cytotoxic effects of gossypol enantiomers and gossypolone in tumour cell lines. Cancer Lett., 1999, 135, 171-180.
[http://dx.doi.org/10.1016/S0304-3835(98)0030-4] [PMID: 10096426]
[35]
Yu, Y. Probing into the mechanism of action, metabolism and toxicity of gossypol by studying its (+)- and (–)- stereoisomers. Ethnopharmacology, 1987, 20, 65-78.
[PMID: 3306161]
[36]
Wu, D. An overview of the clinical pharmacology and therapeutic potential of gossypol as a male contraceptive agent and in gynaecological disease. Drugs, 1989, 38(3), 333-341.
[http://dx.doi.org/10.2165/00003495-198938030-00001] [PMID: 2680434]
[37]
Qian, S.Z.; Wang, Z.G. Gossypol: a potential antifertility agent for males. Annu. Rev. Pharmacol. Toxicol., 1984, 24, 329-360.
[http://dx.doi.org/10.1146/annurev.pa.24.040184.001553] [PMID: 6375548]
[38]
Razakantoanina, V.; Nguyen Kim, P.P.; Jaureguiberry, G. Antimalarial activity of new gossypol derivatives. Parasitol. Res., 2000, 86(8), 665-668.
[http://dx.doi.org/10.1007/PL00008549] [PMID: 10952267]
[39]
Coyle, T.; Levante, S.; Shetler, M.; Winfield, J. In vitro and in vivo cytotoxicity of gossypol against central nervous system tumor cell lines. J. Neurooncol., 1994, 19(1), 25-35.
[http://dx.doi.org/10.1007/BF01051046] [PMID: 7815102]
[40]
Wu, Y.W.; Chik, C.L.; Knazek, R.A. An in vitro and in vivo study of antitumor effects of gossypol on human SW-13 adrenocortical carcinoma. Cancer Res., 1989, 49(14), 3754-3758.
[PMID: 2736516]
[41]
Tuszynski, G.P.; Cossu, G. Differential cytotoxic effect of gossypol on human melanoma, colon carcinoma, and other tissue culture cell lines. Cancer Res., 1984, 44(2), 768-771.
[PMID: 6581864]
[42]
Yu, Y.; Deck, J.A.; Hunsaker, L.A.; Deck, L.M.; Royer, R.E.; Goldberg, E.; Vander Jagt, D.L. Selective active site inhibitors of human lactate dehydrogenases A4, B4, and C4. Biochem. Pharmacol., 2001, 62(1), 81-89.
[http://dx.doi.org/10.1016/S0006-2952(01)00636-0] [PMID: 11377399]
[43]
Vander Jagt, D.L.; Deck, L.M.; Royer, R.E. Gossypol: prototype of inhibitors targeted to dinucleotide folds. Curr. Med. Chem., 2000, 7(4), 479-498.
[http://dx.doi.org/10.2174/0929867003375119] [PMID: 10702620]
[44]
Gomez, M.S.; Piper, R.C.; Hunsaker, L.A.; Royer, R.E.; Deck, L.M.; Makler, M.T.; Vander Jagt, D.L. Substrate and cofactor specificity and selective inhibition of lactate dehydrogenase from the malarial parasite P. falciparum. Mol. Biochem. Parasitol., 1997, 90(1), 235-246.
[http://dx.doi.org/10.1016/S0166-6851(97)00140-0] [PMID: 9497046]
[45]
Ikeda, M. Inhibition kinetics of NAD-linked enzymes by gossypol acetic acid. Andrologia, 1990, 22(5), 409-416.
[http://dx.doi.org/10.1111/j.1439-0272.1990.tb02019.x] [PMID: 2073051]
[46]
Yu, Z.H.; Chan, H.C. Gossypol as a male antifertility agent--why studies should have been continued. Int. J. Androl., 1998, 21(1), 2-7.
[http://dx.doi.org/10.1046/j.1365-2605.1998.00091.x] [PMID: 9639145]
[47]
Yu, Z.H.; Chan, H.C. Gossypol and hypokalemia: a critical review. Adv. Contracept. Deliv. Syst., 1994, 10(1-2), 23-33.
[PMID: 12289957]
[48]
Qian, S.Z.; Jing, G.W.; Wu, X.Y.; Xu, Y.; Li, Y.Q.; Zhou, Z.H. Gossypol related hypokalemia. Clinicopharmacologic studies. Chin. Med. J. (Engl.), 1980, 93(7), 477-482.
[PMID: 6772395]
[49]
Jaroszewski, J.W.; Kaplan, O.; Cohen, J.S. Action of gossypol and rhodamine 123 on wild type and multidrug-resistant MCF-7 human breast cancer cells: 31P nuclear magnetic resonance and toxicity studies. Cancer Res., 1990, 50(21), 6936-6943.
[PMID: 2208159]
[50]
Deck, L.M.; Royer, R.E.; Chamblee, B.B.; Hernandez, V.M.; Malone, R.R.; Torres, J.E.; Hunsaker, L.A.; Piper, R.C.; Makler, M.T.; Vander Jagt, D.L. Selective inhibitors of human lactate dehydrogenases and lactate dehydrogenase from the malarial parasite Plasmodium falciparum. J. Med. Chem., 1998, 41(20), 3879-3887.
[http://dx.doi.org/10.1021/jm980334n] [PMID: 9748363]
[51]
Dutta, P.; Le, A.; Vander Jagt, D.L.; Tsukamoto, T.; Martinez, G.V.; Dang, C.V.; Gillies, R.J. Evaluation of LDH-A and glutaminase inhibition in vivo by hyperpolarized 13C-pyruvate magnetic resonance spectroscopy of tumors. Cancer Res., 2013, 73(14), 4190-4195.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0465] [PMID: 23722553]
[52]
Le, A.; Cooper, C.R.; Gouw, A.M.; Dinavahi, R.; Maitra, A.; Deck, L.M.; Royer, R.E.; Vander Jagt, D.L.; Semenza, G.L.; Dang, C.V. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc. Natl. Acad. Sci. USA, 2010, 107(5), 2037-2042.
[http://dx.doi.org/10.1073/pnas.0914433107] [PMID: 20133848]
[53]
Somei, M. 1-Hydroxyindoles. Heterocycles, 1999, 50, 1157-1211.
[http://dx.doi.org/10.3987/REV-98-SR(H)8]
[54]
Xu, L.; Farthing, A.K.; Dropinski, J.F.; Meinke, P.T.; McCallum, C.; Hickey, E.; Liu, K. Synthesis and antibacterial activity of novel water-soluble nocathiacin analogs. Bioorg. Med. Chem. Lett., 2013, 23(1), 366-369.
[http://dx.doi.org/10.1016/j.bmcl.2012.10.065] [PMID: 23164707]
[55]
Granchi, C.; Roy, S.; Mottinelli, M.; Nardini, E.; Campinoti, F.; Tuccinardi, T.; Lanza, M.; Betti, L.; Giannaccini, G.; Lucacchini, A.; Martinelli, A.; Macchia, M.; Minutolo, F. Synthesis of sulfonamide-containing N-hydroxyindole-2-carboxylates as inhibitors of human lactate dehydrogenase-isoform 5. Bioorg. Med. Chem. Lett., 2011, 21(24), 7331-7336.
[http://dx.doi.org/10.1016/j.bmcl.2011.10.031] [PMID: 22056743]
[56]
Granchi, C.; Roy, S.; De Simone, A.; Salvetti, I.; Tuccinardi, T.; Martinelli, A.; Macchia, M.; Lanza, M.; Betti, L.; Giannaccini, G.; Lucacchini, A.; Giovannetti, E.; Sciarrillo, R.; Peters, G.J.; Minutolo, F. N-Hydroxyindole-based inhibitors of lactate dehydrogenase against cancer cell proliferation. Eur. J. Med. Chem., 2011, 46(11), 5398-5407.
[http://dx.doi.org/10.1016/j.ejmech.2011.08.046] [PMID: 21944286]
[57]
Granchi, C.; Roy, S.; Giacomelli, C.; Macchia, M.; Tuccinardi, T.; Martinelli, A.; Lanza, M.; Betti, L.; Giannaccini, G.; Lucacchini, A.; Funel, N.; León, L.G.; Giovannetti, E.; Peters, G.J.; Palchaudhuri, R.; Calvaresi, E.C.; Hergenrother, P.J.; Minutolo, F. Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells. J. Med. Chem., 2011, 54(6), 1599-1612.
[http://dx.doi.org/10.1021/jm101007q] [PMID: 21332213]
[58]
Shi, Y.; Pinto, B.M. Human lactate dehydrogenase a inhibitors: a molecular dynamics investigation. PLoS One, 2014, 9(1)e86365
[http://dx.doi.org/10.1371/journal.pone.0086365] [PMID: 24466056]
[59]
Di Bussolo, V.; Calvaresi, E.C.; Granchi, C.; Del Bino, L.; Frau, I.; Lang, M.C.; Tuccinardi, T.; Macchia, M.; Martinelli, A.; Hergenrother, P.J.; Minutolo, F. Synthesis and biological evaluation of non-glucose glycoconjugated N-hydroyxindole class LDH inhibitors as anticancer agents. RSC Advances, 2015, 5(26), 19944-19954.
[http://dx.doi.org/10.1039/C5RA00946D] [PMID: 26167277]
[60]
Calvaresi, E.C.; Granchi, C.; Tuccinardi, T.; Di Bussolo, V.; Huigens, R.W., III; Lee, H-Y.; Palchaudhuri, R.; Macchia, M.; Martinelli, A.; Minutolo, F.; Hergenrother, P.J. Dual targeting of the Warburg effect with a glucose-conjugated lactate dehydrogenase inhibitor. ChemBioChem, 2013, 14(17), 2263-2267.
[http://dx.doi.org/10.1002/cbic.201300562] [PMID: 24174263]
[61]
Granchi, C.; Paterni, I.; Rani, R.; Minutolo, F. Small-molecule inhibitors of human LDH5. Future Med. Chem., 2013, 5(16), 1967-1991.
[http://dx.doi.org/10.4155/fmc.13.151] [PMID: 24175747]
[62]
Granchi, C.; Bertini, S.; Macchia, M.; Minutolo, F. Inhibitors of lactate dehydrogenase isoforms and their therapeutic potentials. Curr. Med. Chem., 2010, 17(7), 672-697.
[http://dx.doi.org/10.2174/092986710790416263] [PMID: 20088761]
[63]
Choi, S.R.; Pradhan, A.; Hammond, N.L.; Chittiboyina, A.G.; Tekwani, B.L.; Avery, M.A. Design, synthesis, and biological evaluation of Plasmodium falciparum lactate dehydrogenase inhibitors. J. Med. Chem., 2007, 50(16), 3841-3850.
[http://dx.doi.org/10.1021/jm070336k] [PMID: 17636950]
[64]
Cameron, A.; Read, J.; Tranter, R.; Winter, V.J.; Sessions, R.B.; Brady, R.L.; Vivas, L.; Easton, A.; Kendrick, H.; Croft, S.L.; Barros, D.; Lavandera, J.L.; Martin, J.J.; Risco, F.; García-Ochoa, S.; Gamo, F.J.; Sanz, L.; Leon, L.; Ruiz, J.R.; Gabarró, R.; Mallo, A.; Gómez de las Heras, F. Identification and activity of a series of azole-based compounds with lactate dehydrogenase-directed anti-malarial activity. J. Biol. Chem., 2004, 279(30), 31429-31439.
[http://dx.doi.org/10.1074/jbc.M402433200] [PMID: 15117937]
[65]
Ward, R.A.; Brassington, C.; Breeze, A.L.; Caputo, A.; Critchlow, S.; Davies, G.; Goodwin, L.; Hassall, G.; Greenwood, R.; Holdgate, G.A.; Mrosek, M.; Norman, R.A.; Pearson, S.; Tart, J.; Tucker, J.A.; Vogtherr, M.; Whittaker, D.; Wingfield, J.; Winter, J.; Hudson, K. Design and synthesis of novel lactate dehydrogenase A inhibitors by fragment-based lead generation. J. Med. Chem., 2012, 55(7), 3285-3306.
[http://dx.doi.org/10.1021/jm201734r] [PMID: 22417091]
[66]
Moorhouse, A.D.; Spiteri, C.; Sharma, P.; Zloh, M.; Moses, J.E. Targeting glycolysis: a fragment based approach towards bifunctional inhibitors of hLDH-5. Chem. Commun. (Camb.), 2011, 47(1), 230-232.
[http://dx.doi.org/10.1039/C0CC01166E] [PMID: 20676418]
[67]
Coutinho, J.P.; Cortopassi, W.A.; Oliveira, A.A.; Franca, T.C.C.; Krettli, A.U. Antimalarial activity of potential inhibitors of plasmodium falciparum lactate dehydrogenase enzyme selected by docking studies. PLoS One, 2011, •••e21237
[http://dx.doi.org/10.1371/journal.pone.0021237] [PMID: 21779323]
[68]
Kohlmann, A.; Zech, S.G.; Li, F.; Zhou, T.; Squillace, R.M.; Commodore, L.; Greenfield, M.T.; Lu, X.; Miller, D.P.; Huang, W.S.; Qi, J.; Thomas, R.M.; Wang, Y.; Zhang, S.; Dodd, R.; Liu, S.; Xu, R.; Xu, Y.; Miret, J.J.; Rivera, V.; Clackson, T.; Shakespeare, W.C.; Zhu, X.; Dalgarno, D.C. Fragment growing and linking lead to novel nanomolar lactate dehydrogenase inhibitors. J. Med. Chem., 2013, 56(3), 1023-1040.
[http://dx.doi.org/10.1021/jm3014844] [PMID: 23302067]
[69]
Kotlyar, A.B.; Randazzo, A.; Honbo, N.; Jin, Z.Q.; Karliner, J.S.; Cecchini, G. Cardioprotective activity of a novel and potent competitive inhibitor of lactate dehydrogenase. FEBS Lett., 2010, 584(1), 159-165.
[http://dx.doi.org/10.1016/j.febslet.2009.11.022] [PMID: 19913538]
[70]
Shim, H.; Dolde, C.; Lewis, B.C.; Wu, C-S.; Dang, G.; Jungmann, R.A.; Dalla-Favera, R.; Dang, C.V. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc. Natl. Acad. Sci. USA, 1997, 94(13), 6658-6663.
[http://dx.doi.org/10.1073/pnas.94.13.6658] [PMID: 9192621]
[71]
Qing, G.; Skuli, N.; Mayes, P.A.; Pawel, B.; Martinez, D.; Maris, J.M.; Simon, M.C. Combinatorial regulation of neuroblastoma tumor progression by N-Myc and hypoxia inducible factor HIF-1alpha. Cancer Res., 2010, 70(24), 10351-10361.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-0740] [PMID: 20961996]
[72]
Zhao, D.; Zou, S.W.; Liu, Y.; Zhou, X.; Mo, Y.; Wang, P.; Xu, Y-H.; Dong, B.; Xiong, Y.; Lei, Q-Y.; Guan, K-L. Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer. Cancer Cell, 2013, 23(4), 464-476.
[http://dx.doi.org/10.1016/j.ccr.2013.02.005] [PMID: 23523103]
[73]
Wang, Z.; Wang, D.; Han, S.; Wang, N.; Mo, F.; Loo, T.Y.; Shen, J.; Huang, H.; Chen, J. Bioactivity-guided identification and cell signaling technology to delineate the lactate dehydrogenase A inhibition effects of Spatholobus suberectus on breast cancer. PLoS One, 2013, 8(2)e56631
[http://dx.doi.org/10.1371/journal.pone.0056631] [PMID: 23457597]
[74]
Wang, J.; Wang, H.; Liu, A.; Fang, C.; Hao, J.; Wang, Z. Lactate dehydrogenase A negatively regulated by miRNAs promotes aerobic glycolysis and is increased in colorectal cancer. Oncotarget, 2015, 6(23), 19456-19468.
[http://dx.doi.org/10.18632/oncotarget.3318] [PMID: 26062441]
[75]
Wang, Z-Y.; Loo, T.Y.; Shen, J-G.; Wang, N.; Wang, D-M.; Yang, D-P.; Mo, S-L.; Guan, X-Y.; Chen, J-P. LDH-A silencing suppresses breast cancer tumorigenicity through induction of oxidative stress mediated mitochondrial pathway apoptosis. Breast Cancer Res. Treat., 2012, 131(3), 791-800.
[http://dx.doi.org/10.1007/s10549-011-1466-6] [PMID: 21452021]
[76]
Cui, W.; Lv, W.; Qu, Y.; Ma, R.; Wang, Y-W.; Xu, Y-J.; Wu, D.; Chen, X. Discovery of 2-((3-cyanopyridin-2-yl)thio)acetamides as human lactate dehydrogenase A inhibitors to reduce the growth of MG-63 osteosarcoma cells: Virtual screening and biological validation. Bioorg. Med. Chem. Lett., 2016, 26(16), 3984-3987.
[http://dx.doi.org/10.1016/j.bmcl.2016.06.083] [PMID: 27406795]
[77]
Purkey, H.E.; Robarge, K.; Chen, J.; Chen, Z.; Corson, L.B.; Ding, C.Z.; DiPasquale, A.G.; Dragovich, P.S.; Eigenbrot, C.; Evangelista, M.; Fauber, B.P.; Gao, Z.; Ge, H.; Hitz, A.; Ho, Q.; Labadie, S.S.; Lai, K.W.; Liu, W.; Liu, Y.; Li, C.; Ma, S.; Malek, S.; O’Brien, T.; Pang, J.; Peterson, D.; Salphati, L.; Sideris, S.; Ultsch, M.; Wei, B.; Yen, I.; Yue, Q.; Zhang, H.; Zhou, A. Cell active hydroxylactam inhibitors of human lactate dehydrogenase with oral bioavailability in mice. ACS Med. Chem. Lett., 2016, 7(10), 896-901.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00190] [PMID: 27774125]
[78]
Chen, C-Y.; Feng, Y.; Chen, J-Y.; Deng, H. Identification of a potent inhibitor targeting human lactate dehydrogenase A and its metabolic modulation for cancer cell line. Bioorg. Med. Chem. Lett., 2016, 26(1), 72-75.
[http://dx.doi.org/10.1016/j.bmcl.2015.11.025] [PMID: 26597536]
[79]
Tuccinardi, T.; Poli, G.; Corchia, I.; Granchi, C.; Lapillo, M.; Macchia, M.; Minutolo, F.; Ortore, G.; Martinelli, A. A virtual screening study for lactate dehydrogenase 5 inhibitors by using a pharmacophore-based approach. Mol. Inform., 2016, 35(8-9), 434-439.
[http://dx.doi.org/10.1002/minf.201501026] [PMID: 27546047]


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VOLUME: 26
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Year: 2019
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DOI: 10.2174/0929867324666170209103444
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