New synthetic inhibitors of fatty acid synthase with anticancer activity

Journal of Medicinal Chemistry

Volumn 55, Issue 11, 2012, Pages 5013-5023

  Turrado, Carlos ^a   Puig, Teresa ^b,e   García Cárceles, Javier ^a   Artola, Marta ^a   Benhamú, Bellinda ^a   Ortega Gutiérrez, Silvia ^a   Relat, Joana ^c   Oliveras, Gloria ^b,e   Blancafort, Adriana ^b,e   Haro, Diego ^c   Marrero, Pedro F ^c   Colomer, Ramón ^d   López Rodríguez, María L ^a  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^b GIRONA BIOMEDICAL RESEARCH INSTITUTE IDIBGI   (Spain)

^c UNIVERSITY OF BARCELONA   (Spain)

^d Centro Nacional de Investigaciones Oncológicas   (Spain)

^e UNIVERSITY OF GIRONA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

1,2 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]BENZENE; 1,2 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]CYCLOHEXANE; 1,2 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]ETHANE; 1,2 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]NAPHTHALENE; 1,3 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY] 5,6,7,8 TETRAHYDRONAPHTHALENE; 1,3 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]BENZENE; 1,3 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]NAPHTHALENE; 1,4 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY] 1,2,3,4 TETRAHYDRONAPHTHALENE; 1,4 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY] 5,6,7,8 TETRAHYDRONAPHTHALENE; 1,4 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]BENZENE; 1,4 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]NAPHTHALENE; 1,5 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]NAPHTHALENE; 1,6 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]NAPHTHALENE; 1,7 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]NAPHTHALENE; 1,8 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]NAPHTHALENE; 2 METHOXY 1,4 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]BENZENE; 2 METHYL 1,4 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]BENZENE; 2,3 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]NAPHTHALENE; 2,5 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY] 1,1' BIPHENYL; 2,6 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]NAPHTHALENE; 2,7 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]NAPHTHALENE; 4 CARBOXY 5 OCTYL 3 METHYLENEBUTYROLACTONE; 4,4' BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY] 1,1' BIPHENYL; ANTINEOPLASTIC AGENT; CERULENIN; EPIGALLOCATECHIN GALLATE; FATTY ACID SYNTHASE INHIBITOR; METHYL 1,4 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY] 2 NAPHTHOATE; METHYL 2,5 BIS[(3,4,5 TRIHYDROXYBENZOYL)OXY]BENZOATE; POLYPHENOL DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG MECHANISM; DRUG SYNTHESIS; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; MALE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; TUMOR CELL; WEIGHT REDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CARNITINE O-PALMITOYLTRANSFERASE; CELL LINE, TUMOR; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME ACTIVATION; FATTY ACID SYNTHETASE COMPLEX; HUMANS; MALE; MICE; MICE, INBRED C57BL; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; POLYPHENOLS; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR, ERBB-2; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP; WEIGHT LOSS;

EID: 84862293778     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2016045     Document Type: Article

References (30)

1. Abramson, H. N. The lipogenesis pathway as a cancer target J. Med. Chem. 2011, 54, 5615-5638
2. Kuhajda, F. P.; Jenner, K.; Wood, F. D.; Hennigar, R. A.; Jacobs, L. B.; Dick, J. D.; Pasternack, G. R. Fatty acid synthesis: a potential selective target for antineoplastic therapy Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 6379-6383
3. Liu, H.; Liu, J.-Y.; Wu, X.; Zhang, J.-T. Biochemistry, molecular biology, and pharmacology of fatty acid synthase, an emerging therapeutic target and diagnosis/prognosis marker Int. J. Biochem. Mol. Biol. 2010, 18, 69-89
4. Migita, T.; Ruiz, S.; Fornari, A.; Fiorentino, M.; Priolo, C.; Zadra, G.; Inazuka, F.; Grisanzio, C.; Palescandolo, E.; Shin, E.; Fiore, C.; Xie, W.; Kung, A. L.; Febbo, P. G.; Subramanian, A.; Mucci, L.; Ma, J.; Signoretti, S.; Stampfer, M.; Hahn, W. C.; Finn, S.; Loda, M. Fatty acid synthase: a metabolic enzyme and candidate oncogene in prostate cancer J. Natl. Cancer Inst. 2009, 101, 519-532
5. Omura, S. The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis Bacteriol. Rev. 1976, 40, 681-697
6. Lupu, R.; Menendez, J. A. Pharmacological inhibitors of fatty acid synthase (FASN)-catalyzed endogenous fatty acid biogenesis: a new family of anti-cancer agents? Curr. Pharm. Biotechnol. 2006, 7, 483-493
7. Kuhajda, F. P.; Pizer, E. S.; Li, J. N.; Mani, N. S.; Frehywot, G. L.; Townsend, C. A. Synthesis and antitumor activity of an inhibitor of fatty acid synthase Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 3450-3454
8. Rendina, A. R.; Cheng, D. Characterization of the inactivation of rat fatty acid synthase by C75: inhibition of partial reactions and protection by substrates Biochem. J. 2005, 388, 895-903
9. Yang, N.; Kays, J. S.; Skillman, T. R.; Burris, L.; Seng, T. W.; Hammond, C. C75 [4-methylene-2-octyl-5-oxo-tetrahydro-furan-3-carboxylic acid] activates carnitine palmitoyltransferase-1 in isolated mitochondria and intact cells without displacement of bound malonyl CoA J. Pharmacol. Exp. Ther. 2005, 312, 127-133
10. Nicot, C.; Napal, L.; Relat, J.; Gonzalez, S.; Llebaria, A.; Woldegiorgis, G.; Marrero, P. F.; Haro, D. C75 activates malonyl-CoA sensitive and insensitive components of the CPT system Biochem. Biophys. Res. Commun. 2004, 325, 660-664
11. Thupari, J. N.; Landree, L. E.; Ronnett, G. V.; Kuhajda, F. P. C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 9498-9502
12. Kridel, S. J.; Axelrod, F.; Rozenkrantz, N.; Smith, J. W. Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity Cancer Res. 2004, 64, 2070-2075
13. Yang, C. S.; Wang, X.; Lu, G.; Picinich, S. C. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance Nature Rev. Drug Discovery 2009, 9, 429-439
14. Wang, X.; Tian, W. Green tea epigallocatechin gallate: a natural inhibitor of fatty-acid synthase Biochem. Biophys. Res. Commun. 2001, 288, 1200-1206
15. Brusselmans, K.; De Schrijver, E.; Heyns, W.; Verhoeven, G.; Swinnen, J. V. Epigallocatechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells Int. J. Cancer 2003, 106, 856-862
16. Vergote, D.; Cren-Olive, C.; Chopin, V.; Toillon, R. A.; Rolando, C.; Hondermarck, H.; Le Bourhis, X. (-)-Epigallocatechin (EGC) of green tea induces apoptosis of human breast cancer cells but not of their normal counterparts Breast Cancer Res. Treat. 2002, 76, 195-201
17. Puig, T.; Vazquez-Martin, A.; Relat, J.; Petriz, J.; Menendez, J. A.; Porta, R.; Casals, G.; Marrero, P. F.; Haro, D.; Brunet, J.; Colomer, R. Fatty acid metabolism in breast cancer cells: differential inhibitory effects of epigallocatechin gallate (EGCG) and C75 Breast Cancer Res. Treat. 2008, 109, 471-479
18. Nakagawa, K.; Miyazawa, T. Chemiluminescence-high-performance liquid chromatographic determination of tea catechin, (-)-epigallocatechin 3-gallate, at picomole levels in rat and human plasma Anal. Biochem. 1997, 248, 41
19. Colomer, R; Puig, T.; Brunet, J.; López-Rodríguez, M. L.; Benhamú, B.; Ortega-Gutiérrez, S.; Turrado, C. PCT/EP2008/058099, WO 2009/000864 A1, 2009.
20. Puig, T.; Turrado, C.; Benhamú, B.; Aguilar, H.; Relat, J.; Ortega-Gutiérrez, S.; Casals, G.; Marrero, P. F.; Urruticoechea, A.; Haro, D.; López-Rodríguez, M. L.; Colomer, R. Novel inhibitors of fatty acid synthase with anticancer activity Clin. Cancer Res. 2009, 15, 7608-7615
21. Ren, Y.; Himmeldirk, K.; Chen, X. Synthesis and structure-activity relationship study of antidiabetic penta- O -galloyl- d -glucopyranose and its analogs J. Med. Chem. 2006, 49, 2829-2837
22. Nakazono, M.; Ma, L.; Zaitsu, K. Synthesis of poly(3,4,5- trihydroxybenzoate ester)dendrimers and their chemiluminescence Tetrahedron Lett. 2002, 43, 8185-8189
23. Feldman, K. S.; Sambandam, A.; Bowers, K. E.; Appel, H. M. Probing the role of polyphenol oxidation in mediating insect-pathogen interactions. Galloyl-derived electrophilic traps for the Lymantria dispar nuclear polyhedrosis virus matrix protein polyhedrin J. Org. Chem. 1999, 64, 5794-5803
24. Kündig, E. P.; Enriquez-Garcia, A. Diastereoselective and enantioselective reduction of tetralin-1,4-dione. Beilstein J. Org. Chem. 2008, 4, doi: 10.3762/bjoc.4.37.
25. Fieser, L. F.; Fieser, M. The synthesis from β-naphthohydroquinone of a tautomer of 4-benzyl-1,2-naphthoquinone J. Am. Chem. Soc. 1939, 61, 596-608
26. Adams, S. P.; Whitlock, H. W., Jr. Synthesis, conformation, and complexation behavior of 2,9,18,25-tetraoxa[8.8](1,4)naphthalenophane J. Org. Chem. 1971, 46, 3474-3478
27. 2 complexes to dihydroxydiones of tetracene and perylene: novel electron acceptors showing n-type semiconducting behavior Org. Lett. 2009, 11, 149-152
28. Menendez, J. A.; Vellon, L.; Mehmi, I.; Oza, B. P.; Ropero, S.; Colomer, R.; Lupu, R. Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 10715-10720
29. Gooding, O. W.; Vo, L.; Bhattacharyya, S.; Labadie, J. W. Use of statistical design of experiments in the optimization of amide synthesis utilizing polystyrene-supported N -hydroxybenzotriazole resin J. Comb. Chem. 2002, 4, 576-583
30. Loftus, T. M.; Jaworsky, D. E.; Frehywot, G. L.; Townsend, C. A.; Ronnett, G. V.; Lane, M. D.; Kuhajda, F. P. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors Science 2000, 288, 2379-2381