Journal of Medicinal Chemistry
ARTICLE
Park, H. W.; Inglese, J.; Cantley, L. C.; Auld, D. S.; Thomas, C. J.
Evaluation of substituted N,N0-diarylsulfonamides as activators of the
tumor cell specific M2 isoform of pyruvate kinase. J. Med. Chem. 2010,
53, 1048–1055.
(30) 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. U.S.A. 2010, 107,
2037–2042.
(31) 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, 175–185.
(32) Somei, M. 1-Hydroxyindoles. Heterocycles 1999, 50, 1157–
1211.
(18) (a) Koukorakis, M. I.; Giatromanolaki, A.; Simopoulos, C.;
Polychronidis, A.; Sivridis, E. Lactate dehydrogenase 5 (LDH5)
relates to up-regulated hypoxia inducible factor pathway and meta-
stasis in colorectal cancer. Clin. Exp. Metastasis 2005, 22, 25–30. (b)
Koukorakis, M. I.; Pitiakoudis, M.; Giatromanolaki, A.; Tsarouha, A.;
Polychronidis, A.; Sivridis, E.; Simopoulos, C. Oxygen and glucose
consumption in gastrointestinal adenocarcinomas: correlation with
markers of hypoxia, acidity and anaerobic glycolysis. Cancer Sci. 2006,
97, 1056–1060. (c) Kolev, Y.; Uetake, H.; Takagi, Y.; Sugihara, K.
Lactate dehydrogenase-5 (LDH-5) expression in human gastric
cancer: association with hypoxia-inducible factor (HIF-1R) pathway,
angiogenic factors production and poor prognosis. Ann. Surg. Oncol.
2008, 15, 2336–2344.
(19) Koukourakis, M. I.; Giatromanolaki, A.; Sivridis, E.; Bougiou-
kas, G.; Didilis, V.; Gatter, K. C.; Harris, A. L. Lactate dehydrogenase-5
(LDH-5) overexpression in non-small-cell lung cancer tissues is linked
to tumour hypoxia, angiogenic factor production and poor prognosis. Br.
J. Cancer 2003, 89, 877–885.
(20) (a) Sørensen, B. S.; Hao, J.; Overgaard, J.; Vorum, H.; Honorꢀe,
B.; Alsner, J.; Horsman, M. R. Influence of oxygen concentration and pH
on expression of hypoxia induced genes. Radiother. Oncol. 2005, 76,
187–193. (b) Sørensen, B. S.; Alsner, J.; Overgaard, J.; Horsman, M. R.
Hypoxia induced expression of endogenous markers in vitro is highly
influenced by pH. Radiother. Oncol. 2007, 83, 362–366.
(21) (a) Lardner, A. The effects of extracellular pH on immune
function. J. Leukocyte Biol. 2001, 69, 522–530. (b) Fischer, K.;
Hoffmann, P.; Voelkl, S.; Meidenbauer, N.; Ammer, J.; Edinger, M.;
Gottfried, E.; Schwarz, S.; Rothe, G.; Hoves, S.; Renner, K.; Timischl, B.;
Mackensen, A.; Kunz-Schughart, L.; Andreesen, R.; Krause, S. W.;
Kreutz, M. Inhibitory effect of tumor cell-derived lactic acid on human
T cells. Blood 2007, 109, 3812–3819.
(22) Fantin, V. R.; St-Pierre, J.; Leder, P. Attenuation of LDH-A
expression uncovers a link between glycolysis, mitochondrial physiol-
ogy, and tumor maintenance. Cancer Cell 2006, 9, 425–434.
(23) Zhou, M.; Zhao, Y.; Ding, Y.; Liu, H.; Liu, Z.; Fodstad, O.;
Riker, A. I.; Kamarajugadda, S.; Lu, J.; Owen, L. B.; Ledoux, S. P.; Tan,
M. Warburg effect in chemosensitivity: targeting lactate dehydrogen-
ase-A re-sensitizes Taxol-resistant cancer cells to Taxol. Mol. Cancer
2010, 9, 33.
(24) Kanno, T.; Sudo, K.; Maekawa, M.; Nishimura, Y.; Ukita, M.;
Fukutake, K. Lactate dehydrogenase M-subunit deficiency: a new type of
hereditary exertional myopathy. Clin. Chim. Acta 1988, 173, 89–98.
(25) Granchi, C.; Bertini, S.; Macchia, M.; Minutolo, F. Inhibitors of
lactate dehydrogenase isoforms and their therapeutic potentials. Curr.
Med. Chem. 2010, 17, 672–697.
(26) Thornburg, J. M.; Nelson, K. K.; Clem, B. F.; Lane, A. N.;
Arumugam, S.; Simmons, A.; Eaton, J. W.; Telang, S.; Chesney, J.
Targeting aspartate aminotransferase in breast cancer. Breast Cancer Res.
2008, 10, R84.
(33) Bagley, M. C.; Dale, J. W.; Merritt, E. A.; Xiong, X. Thiopeptide
antibiotics. Chem. Rev. 2005, 105, 685–714.
(34) Somei, M. Recent advances in the chemistry of 1-hydroxyin-
doles, 1-hydroxytryptophans, and 1-hydroxytryptamines. Adv. Hetero-
cycl. Chem. 2002, 82, 101–155.
(35) Nicolaou, K. C.; Estrada, A. A.; Freestone, G. C.; Lee, S. H.;
Alvarez-Mico, X. New synthetic technology for the construction of N-
hydroxyindoles and synthesis of nocathiacin I model systems. Tetrahe-
dron 2007, 63, 6088–6114.
(36) Bykov, E. E.; Lavrenov, S. N.; Preobrazhenskaya, M. N. Quan-
tum-chemical investigation of the dependence of pKa on the calculated
energy of proton removal for certain derivatives of indole and phenol.
Chem. Heterocycl. Compd. 2006, 42, 42–44.
(37) Entwistle, I. D.; Gilkerson, T.; Johnstone, R. A. W.; Telford,
R. P. Rapid catalytic transfer reduction of aromatic nitro compounds to
hydroxylamines. Tetrahedron 1978, 34, 213–215.
(38) Hume, W. E.; Tokunaga, T.; Nagata, R. A concise and
regioselective synthesis of 6-iodo-4-trifluoromethylisatin, an intermedi-
ate in the synthesis of the novel, non-peptidyl growth hormone
secretagogue SM-130686. Tetrahedron 2002, 58, 3605–3611.
(39) Leadbeater, N. E.; Marco, M. Ligand-free palladium catalysis of
the Suzuki reaction in water using microwave heating. Org. Lett. 2002, 4,
2973–2976.
(40) Demko, Z. P.; Sharpless, K. B. Preparation of 5-substituted 1H-
tetrazoles from nitriles in water. J. Org. Chem. 2001, 66, 7945–7950.
(41) Verdonk, M. L.; Cole, J. C.; Hartshorn, M. J.; Murray, C. W.;
Taylor, R. D. Improved protein-ligand docking using GOLD. Proteins
2003, 52, 609–623.
(42) Conners, R.; Schambach, F.; Read, J.; Cameron, A.; Sessions,
R. B.; Vivas, L.; Easton, A.; Croft, S. L.; Brady, R. L. Mapping the binding
site for gossypol-like inhibitors of Plasmodium falciparum lactate dehy-
drogenase. Mol. Biochem. Parasitol. 2005, 142, 137–148.
(43) DeBerardinis, R. J.; Mancuso, A.; Daikhin, E.; Nissim, I.;
Yudkoff, M.; Wehrli, S.; Thompson, C. B. Beyond aerobic glycolysis:
transformed cells can engage in glutamine metabolism that exceeds the
requirement for protein and nucleotide synthesis. Proc. Natl. Acad. Sci. U.
S.A. 2007, 104, 19345–19350.
(44) Noordhuis, P.; Laan, A. C.; van de Born, K.; Losekoot, N.;
Kathmann, I.; Peters, G. J. Oxaliplatin activity in selected and unselected
human ovarian and colorectal cancer cell lines. Biochem. Pharmacol.
2008, 76, 53–61.
(45) Grieve, W. S. M.; Hey, D. H. Substitution in compounds contain-
ing two or more phenyl groups. II. The nitration of 3-methylbiphenyl. J.
Chem. Soc. 1932, 2245–2247.
(27) Vander Jagt, D. L.; Deck, L. M.; Royer, R. E. Gossypol:
prototype of inhibitors targeted to dinucleotide folds. Curr. Med. Chem
2000, 7, 479–498.
(28) 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.; Gabarrꢀo, R.; Mallo, A.; Gꢀomez 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, 31429–31439.
(29) 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, 3879–3887.
(46) Suryadevara, P. K.; Olepu, S.; Lockman, J. W.; Ohkanda, J.;
Karimi, M.; Verlinde, C. L. M. J.; Kraus, J. M.; Schoepe, J.; Van Voorhis,
W. C.; Hamilton, A. D.; Buckner, F. S.; Gelb, M. H. Structurally simple
inhibitors of lanosterol 14R-demethylase are efficacious in a rodent
model of acute chagas disease. J. Med. Chem. 2009, 52, 3703–3715.
(47) Cesario, C.; Miller, M. J. Pd(0)/InI-mediated allylic additions
to 4-acetoxy-2-azetidinone: new route to highly functionalized carbo-
cyclic scaffolds. Org. Lett. 2009, 11, 1293–1295.
(48) Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat,
T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data
Bank. Nucleic Acids Res. 2000, 28, 235–242.
(49) Swiderek, K.; Panczakiewicz, A.; Bujacz, A.; Bujacz, G.; Paneth,
P. Modeling of isotope effects on binding oxamate to lactic dehydro-
genase. J. Phys. Chem. B 2009, 113, 12782–12789.
1611
dx.doi.org/10.1021/jm101007q |J. Med. Chem. 2011, 54, 1599–1612