Discovery of a new binding site on human choline kinase α1: Design, synthesis, crystallographic studies, and biological evaluation of asymmetrical bispyridinium derivatives

Journal of Medicinal Chemistry

Volumn 57, Issue 2, 2014, Pages 507-515

  Rubio Ruiz, Belén ^a   Figuerola Conchas, Ainoa ^b,c   Ramos Torrecillas, Javier ^d   Capitán Cañadas, Fermín ^a   Ríos Marco, Pablo ^e   Carrasco, Ma Paz ^e   Gallo, Miguel Ángel ^a   Espinosa, Antonio ^a   Marco, Carmen ^e   Ruiz, Concepción ^d   Entrena, Antonio ^a   Hurtado Guerrero, Ramon ^b,c   Conejo García, Ana ^a  

^a UNIVERSITY OF GRANADA   (Spain)

^b INSTITUTO DE QUÍMICA FÍSICA ROCASOLANO   (Spain)

^c FUNDACIÓN ARAID   (Spain)

^d UNIVERSITY OF GRANADA   (Spain)

^e UNIVERSITY OF GRANADA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

4 (4 CHLORO N METHYLANILINO) 1 [4 ((4 DIMETHYLAMINOPYRIDINIUM 1 YL)METHYL)BENZYL]PYRIDINIUM DIBROMIDE; 4 (4 CHLORO N METHYLANILINO) 1 [4 ((4 PYRROLIDINOPYRIDINIUM 1 YL)METHYL)BENZYL]PYRIDINIUM DIBROMIDE; 4 (4 CHLORO N METHYLANILINO) 1 [4 ((4 PYRROLIDINOPYRIDINIUM 1 YL)METHYL)PHENETHYL)BENZYL]PYRIDINIUM DIBROMIDE; 4 (4 CHLORO N METHYLANILINO) 1 [4 ((4 PYRROLIDINOPYRIDINIUM 1 YL)METHYL)PHENYL)BENZYL]PYRIDINIUM DIBROMIDE; 4 (4 CHLORO N METHYLANILINO) 1 [4 ((4 PYRROLIDINOPYRIDINIUM 1 YL)METHYL)PHENYL)BUTYL)BENZYL]PYRIDINIUM DIBROMIDE; 4 (4 CHLORO N METHYLANILINO) 1 [4 (4 ((4 DIMETHYLAMINOPYRIDINIUM 1 YL)METHYL)PHENYL)BENZYL]PYRIDINIUM DIBROMIDE; 4 (4 CHLORO N METHYLANILINO) 1 [4 (4 ((4 DIMETHYLAMINOPYRIDINIUM 1YL)METHYL)PHENETHYL)BENZYL]PYRIDINIUM DIBROMIDE; 4 (4 CHLORO N METHYLANILINO) 1 [4 (4 (4 ((4 DIMETHYLAMINOPYRIDINIUM 1 YL)METHYL)PHENYL)BUTYL)BENZYL]PYRIDINIUM DIBROMIDE; 4 (DIMETHYLAMINO) 1 [4 ((4 PYRROLIDINOPYRIDINIUM 1 YL)METHYL)BENZYL]PYRIDINIUM DIBROMIDE; 4 (DIMETHYLAMINO) 1 [4 (4 ((4 PYRROLIDINOPYRIDINIUM 1 YL)METHYL)PHENETHYL)BENZYL]PYRIDINIUM DIBROMIDE; 4 (DIMETHYLAMINO) 1 [4 (4 ((4 PYRROLIDINOPYRIDINIUM 1 YL)METHYL)PHENYL)BENZYL]PYRIDINIUM DIBROMIDE; 4 (DIMETHYLAMINO) 1 [4 (4 (4 ((4 PYRROLIDINOPYRIDINIUM 1 YL)METHYL)PHENYL)BUTYL)BENZYL]PYRIDINIUM DIBROMIDE; ANTINEOPLASTIC AGENT; CASPASE 3; CHOLINE KINASE; CHOLINE KINASE ALPHA 1; PYRIDINIUM DERIVATIVE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CELL ACTIVATION; CELL CYCLE ARREST; CELL CYCLE PROGRESSION; CONCENTRATION RESPONSE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DRUG BINDING SITE; DRUG DESIGN; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVATION; ENZYME INHIBITION; FEMALE; HELA CELL; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BINDING SITES; CASPASE 3; CELL PROLIFERATION; CHOLINE KINASE; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME ACTIVATION; HELA CELLS; HUMANS; MOLECULAR DOCKING SIMULATION; PYRIDINES;

EID: 84893101859     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm401665x     Document Type: Article

References (26)

1. Gibellini, F.; Smith, T. K. The Kennedy pathway: De novo synthesis of phosphatidylethanolamine and phosphatidylcholine IUBMB Life 2010, 62, 414-428
2. Aoyama, C.; Liao, H.; Ishidate, K. Structure and function of choline kinase isoforms in mammalian cells Prog. Lipid Res. 2004, 43, 266-281 (Pubitemid 38299195)
3. Glunde, K.; Bhujwalla, Z. M.; Ronen, S. M. Choline metabolism in malignant transformation Nat. Rev. Cancer 2011, 11, 835-848
4. Campos, J. M.; Sánchez-Martín, R. M.; Conejo-García, A.; Entrena, A.; Gallo, M. A.; Espinosa, A. (Q)SAR studies to design new human choline kinase inhibitors as antiproliferative drugs Curr. Med. Chem. 2006, 13, 1231-1248
5. Campos, J.; Núñez, M. C.; Conejo-García, A.; Sánchez-Martín, R. M.; Hernández-Alcoceba, R.; Rodríguez-González, A.; Lacal, J. C.; Gallo, M. A.; Espinosa, A. QSAR-derived choline kinase inhibitors: How rational can antiproliferative drug design be? Curr. Med. Chem. 2003, 10, 1095-1112 (Pubitemid 36758224)
6. Conejo-García, A.; Bañez-Coronel, M.; Sánchez- Martín, R.; Rodríguez-González, A.; Ramos, A.; Ramírez de Molina, A.; Espinosa, A.; Gallo, M. A.; Campos, J.; Lacal, J. C. Influence of the linker in bispyridium compounds on the inhibition of human choline kinase J. Med. Chem. 2004, 47, 5433-5440 (Pubitemid 39386296)
7. Malito, E.; Sekulic, N.; Too, W. C.; Konrad, M.; Lavie, A. Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine J. Mol. Biol. 2006, 364, 136-151 (Pubitemid 44649251)
8. Rubio-Ruiz, B.; Conejo-García, A.; Ríos-Marco, P.; Carrasco-Jiménez, M. P.; Segovia, J.; Marco, C.; Gallo, M. A.; Espinosa, A.; Entrena, A. Design, synthesis, theoretical calculations and biological evaluation of new non-symmetrical choline kinase inhibitors Eur. J. Med. Chem. 2012, 50, 154-162
9. Sahún-Roncero, M.; Rubio-Ruiz, B.; Saladino, G.; Conejo-García, A.; Espinosa, A.; Velázquez-Campoy, A.; Gervasio, F. L.; Entrena, A.; Hurtado-Guerrero, R. The mechanism of allosteric coupling in choline kinase α1 revealed by the action of a rationally designed inhibitor Angew. Chem., Int. Ed. 2013, 52, 4582-4586
10. Sahún-Roncero, M.; Rubio-Ruiz, B.; Conejo-Garcia, A.; Velazquez-Campoy, A.; Entrena, A.; Hurtado-Guerrero, R. Determination of potential scaffolds for human choline kinase α1 by chemical deconvolution studies ChemBioChem 2013, 14, 1291-1295
11. Conejo-García, A.; Campos, J.; Sánchez, R. M.; Rodríguez-González, A.; Lacal, J. C.; Gallo, M. A.; Espinosa, A. Choline kinase inhibitory effect and antiproliferative activity of new 1,1′,1″-(benzene-1,3,5-triylmethylene)tris[4-[(disubstituted)amino] pyridinium] tribromides Eur. J. Med. Chem. 2003, 38, 109-116 (Pubitemid 36197859)
12. Hong, B. S.; Allali-Hassani, A.; Tempel, W.; Finerty, P. J., Jr.; MacKenzie, F.; Dimov, S.; Vedadi, M.; Park, H.-W. Crystal structures of human choline kinase isoforms in complex with hemicholinium-3: Single amino acid near the active site influences inhibitor sensitivity J. Biol. Chem. 2012, 285, 16330-16340
13. Gruber, J.; See Too, W. C.; Wong, M. T.; Lavie, A.; McSorley, T.; Konrad, M. Balance of human choline kinase isoforms is critical for cell cycle regulation: Implications for the development of choline kinase-targeted cancer therapy FEBS J. 2012, 279, 1915-1928
14. Pennati, M.; Campbell, A. J.; Curto, M.; Binda, M.; Cheng, Y.; Wang, L. Z.; Curtin, N.; Golding, B. T.; Griffin, R. J.; Hardcastle, I. R.; Herderson, A.; Zaffaroni, N.; Newell, D. R. Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: A possible role for survivin down-regulation Mol. Cancer Ther. 2005, 4, 1328-1337
15. Galluzzi, L.; Vitale, I.; Abrams, J. M.; Alnemri, E. S.; Baehrecke, E. H.; Blagosklonny, M. V.; Dawson, T. M.; Dawson, V. L.; El-Deiry, W. S.; Fulda, S.; Gottlieb, E.; Green, D. R.; Hengartner, M. O.; Kepp, O.; Knight, R. A.; Kumar, S.; Lipton, S. A.; Lu, X.; Madeo, F.; Malorni, W.; Mehlen, P.; Nuñez, G.; Peter, M. E.; Piacentini, M.; Rubinsztein, D. C.; Shi, Y.; Simon, H.-U.; Vandenabeele, P.; White, E.; Yuan, J.; Zhivotovsky, B.; Melino, G.; Kroemer, G. Molecular definitions of cell death subroutines: Recommendations of the Nomenclature Committee on Cell Death 2012 Cell Death Differ. 2012, 19, 107-120
16. Schrödinger Suite 2012; Schrödinger LLC: New York, 2012.
17. The PyMOL Molecular Graphics System, version 1.4; Schrödinger, LLC: New York, 2011.
18. Jiménez-López, J. M.; Carrasco, M. P.; Segovia, J. L.; Marco, C. Hexadecylphosphocholine inhibits phosphatidylcholine biosynthesis and the proliferation of HepG2 cells Eur. J. Biochem. 2002, 269, 4649-4655
19. Kabsch, W. XDS Acta Crystallogr. 2010, D66, 125-132
20. Collaborative Computational Project, Number 4 The CCP4 suite: Programs for protein crystallography Acta Crystallogr. 1994, D50, 760-763
21. Emsley, P.; Cowtan, K. Coot: Model-building tools for molecular graphics Acta Crystallogr. 2004, D60, 2126-2132 (Pubitemid 41742764)
22. Laskowski, R. A.; Moss, D. S.; Thornton, J. M. Main-chain bond lengths and bond angles in protein structures J. Mol. Biol. 1993, 231, 1049-1067 (Pubitemid 23209879)
23. Mossman, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays J. Immunol. Methods 1983, 65, 55-63
24. Vermes, I.; Haanen, C.; Steffens-Nakken, H.; Reutelingsperger, C. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V J. Immunol. Methods 1995, 184, 39-51
25. Gu, Q.; Xing, J. Z.; Huang, M.; Zhang, X.; Chen, J. Nanoformulation of paclitaxel to enhance cancer therapy J. Biomater. Appl. 2013, 2, 298-307
26. Smith, P. K.; Krohn, R. I.; Hermanson, G. T.; Mallia, A. K.; Gartner, F. H.; Provenzano, M. D.; Fujimoto, E. K.; Goeke, N. M.; Bolson, B. J.; Klenk, D. C. Measurement of protein using bicinchoninic acid Anal. Biochem. 1985, 150, 76-85 (Pubitemid 16258399)