Establishment of a structure-activity relationship of 1 H-imidazo[4,5-c]quinoline-based kinase inhibitor NVP-BEZ235 as a lead for African sleeping sickness

Journal of Medicinal Chemistry

Volumn 57, Issue 11, 2014, Pages 4834-4848

  Seixas, João D ^a,b   Luengo Arratta, Sandra A ^a,b   Diaz, Rosario ^b   Saldivia, Manuel ^b   Rojas Barros, Domingo I ^b   Manzano, Pilar ^c   Gonzalez, Silvia ^c   Berlanga, Manuela ^c   Smith, Terry K ^d   Navarro, Miguel ^b   Pollastri, Michael P ^a  

^a NORTHEASTERN UNIVERSITY   (United States)

^b INSTITUTO DE PARASITOLOGÍA Y BIOMEDICINA LÓPEZ NEYRA   (Spain)

^c GLAXOSMITHKLINE   (Spain)

^d UNIVERSITY OF ST ANDREWS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DACTOLISIB; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE;

AFRICAN TRYPANOSOMIASIS; ANTIPROTOZOAL ACTIVITY; ARTICLE; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DRUG EXPOSURE; DRUG POTENCY; DRUG SELECTIVITY; DRUG SOLUBILITY; ENZYME INHIBITION; HOST CELL; HUMAN; HUMAN CELL; LIPIDOMICS; NONHUMAN; PHENOTYPE; PHOSPHOLIPIDOMICS; PHYSICAL CHEMISTRY; STRUCTURE ACTIVITY RELATION; TRYPANOSOMA BRUCEI;

CYTOTOXINS; HEP G2 CELLS; HUMANS; IMIDAZOLES; MOLECULAR DOCKING SIMULATION; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHOLIPIDS; QUINOLINES; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP; TOR SERINE-THREONINE KINASES; TRYPANOCIDAL AGENTS; TRYPANOSOMA BRUCEI BRUCEI; TRYPANOSOMIASIS, AFRICAN;

EID: 84902491235     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500361r     Document Type: Article

References (31)

1. World Health Organization. Sustaining the drive to overcome the global impact of neglected tropical diseases. http://apps.who.int/iris/bitstream/10665/ 77950/1/9789241564540-eng.pdf (accessed April 22, 2014).
2. Jacobs, R. T.; Nare, B.; Phillips, M. A. State of the art in African trypanosome drug discovery Curr. Top. Med. Chem. 2011, 11, 1255-1274
3. Target Product Profile for Human African Trypanosomiasis. http://www.dndi.org/diseases-projects/diseases/hat/target-product-profile.html (accessed March 23, 2013).
4. Pollastri, M. P.; Campbell, R. K. Target repurposing for neglected diseases Future Med. Chem. 2011, 3, 1307-1315
5. Page, T. H.; Smolinska, M.; Gillespie, J.; Urbaniak, A. M.; Foxwell, B. M. Tyrosine kinases and inflammatory signalling Curr. Mol. Med. 2009, 9, 69-85
6. Ito, K.; Caramori, G.; Adcock, I. M. Therapeutic potential of phosphatidylinositol 3-kinase inhibitors in inflammatory respiratory disease J. Pharmacol. Exp. Ther. 2007, 321, 1-8 (Pubitemid 46456952)
7. Chahrour, O.; Cairns, D.; Omran, Z. Small molecule kinase inhibitors as anti-cancer therapeutics Mini-Rev. Med. Chem. 2012, 12, 399-411
8. Hopkins, A. L.; Groom, C. R. The druggable genome Nat. Rev. Drug. Discovery 2002, 1, 727-730 (Pubitemid 37361545)
9. Johannessen, L. E.; Ringerike, T.; Molnes, J.; Madshus, I. H. Epidermal growth factor receptor efficiently activates mitogen-activated protein kinase in HeLa cells and Hep2 cells conditionally defective in clathrin-dependent endocytosis Exp. Cell Res. 2000, 260, 136-145
10. Naula, C.; Parsons, M.; Mottram, J. C. Protein kinases as drug targets in trypanosomes and Leishmania Biochim. Biophys. Acta 2005, 1754, 151-159 (Pubitemid 41797695)
11. Oduor, R. O.; Ojo, K. K.; Williams, G. P.; Bertelli, F.; Mills, J.; Maes, L.; Pryde, D. C.; Parkinson, T.; Van Voorhis, W. C.; Holler, T. P. Trypanosoma brucei glycogen synthase kinase-3, a target for anti-trypanosomal drug development: A public-private partnership to identify novel leads PLoS Neglected Trop. Dis. 2011, 5, e1017
12. Diaz-Gonzalez, R.; Kuhlmann, F. M.; Galan-Rodriguez, C.; Madeira da Silva, L.; Saldivia, M.; Karver, C. E.; Rodriguez, A.; Beverley, S. M.; Navarro, M.; Pollastri, M. P. The susceptibility of trypanosomatid pathogens to PI3/mTOR kinase inhibitors affords a new opportunity for drug repurposing PLoS Neglected Trop. Dis. 2011, 5, e1297
13. Ochiana, S. O.; Pandarinath, V.; Wang, Z.; Kapoor, R.; Ondrechen, M. J.; Ruben, L.; Pollastri, M. P. The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing Eur. J. Med. Chem. 2013, 62, 777-784
14. Patel, G.; Karver, C. E.; Behera, R.; Guyett, P. J.; Sullenberger, C.; Edwards, P.; Roncal, N. E.; Mensa-Wilmot, K.; Pollastri, M. P. Kinase scaffold repurposing for neglected disease drug discovery: Discovery of an efficacious, lapatanib-derived lead compound for trypanosomiasis J. Med. Chem. 2013, 56, 3820-3832
15. Katiyar, S.; Kufareva, I.; Behera, R.; Thomas, S. M.; Ogata, Y.; Pollastri, M.; Abagyan, R.; Mensa-Wilmot, K. Lapatinib-binding protein kinases in the African trypanosome: identification of cellular targets for kinase-directed chemical scaffolds PLoS One 2013, 8, e56150
16. Maira, S.-M.; Stauffer, F.; Brueggen, J.; Furet, P.; Schnell, C.; Fritsch, C.; Brachmann, S.; Chène, P.; De Pover, A.; Schoemaker, K.; Fabbro, D.; Gabriel, D.; Simonen, M.; Murphy, L.; Finan, P.; Sellers, W.; García-Echeverría, C. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity Mol. Cancer Ther. 2008, 7, 1851-1863
17. Cheng, H.; Li, C.; Bailey, S.; Baxi, S. M.; Goulet, L.; Guo, L.; Hoffman, J.; Jiang, Y.; Johnson, T. O.; Johnson, T. W.; Knighton, D. R.; Li, J.; Liu, K. K. C.; Liu, Z.; Marx, M. A.; Walls, M.; Wells, P. A.; Yin, M.-J.; Zhu, J.; Zientek, M. Discovery of the highly potent PI3K/mTOR dual inhibitor PF-04979064 through structure-based drug design ACS Med. Chem. Lett. 2012, 4, 91-97
18. Wager, T. T.; Hou, X.; Verhoest, P. R.; Villalobos, A. Moving beyond rules: The development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties ACS Chem. Neurosci. 2010, 1, 435-449
19. Engelhardt, H.; Kofink, C.; McConnell, D. Preparation of heterocyclic carboxylic acid amides as PDK1 inhibitors. Patent WO2011131741A1, 2011.
20. Stauffer, F.; Maira, S.-M.; Furet, P.; García-Echeverría, C. Imidazo[4,5-c]quinolines as inhibitors of the PI3K/PKB-pathway Bioorg. Med. Chem. Lett. 2008, 18, 1027-1030 (Pubitemid 351187880)
21. Valko, K.; Bevan, C.; Reynolds, D. Chromatographic hydrophobicity index by fast-gradient RP-HPLC: A high-throughput alternative to log P/log D Anal. Chem. 1997, 69, 2022-2029 (Pubitemid 127698689)
22. Bhattachar, S. N.; Wesley, J. A.; Seadeek, C. Evaluation of the chemiluminescent nitrogen detector for solubility determinations to support drug discovery J. Pharm. Biomed. Anal. 2006, 41, 152-157
23. Wager, T. T.; Chandrasekaran, R. Y.; Hou, X.; Troutman, M. D.; Verhoest, P. R.; Villalobos, A.; Will, Y. Defining desirable central nervous system drug space through the alignment of molecular properties, in vitro ADME, and safety attributes ACS Chem. Neurosci. 2010, 1, 420-434
24. Heffron, T. P.; Salphati, L.; Alicke, B.; Cheong, J.; Dotson, J.; Edgar, K.; Goldsmith, R.; Gould, S. E.; Lee, L. B.; Lesnick, J. D.; Lewis, C.; Ndubaku, C.; Nonomiya, J.; Olivero, A. G.; Pang, J.; Plise, E. G.; Sideris, S.; Trapp, S.; Wallin, J.; Wang, L.; Zhang, X. The design and identification of brain penetrant inhibitors of phosphoinositide 3-kinase α J. Med. Chem. 2012, 55, 8007-8020
25. Hall, B. S.; Gabernet-Castello, C.; Voak, A.; Goulding, D.; Natesan, S. K.; Field, M. C. TbVps34, the trypanosome orthologue of Vps34, is required for Golgi complex segregation J. Biol. Chem. 2006, 281, 27600-27612 (Pubitemid 44401785)
26. Barquilla, A.; Crespo, J. L.; Navarro, M. Rapamycin inhibits trypanosome cell growth by preventing TOR complex 2 formation Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 14579-14584
27. de Jesus, T. C.; Tonelli, R. R.; Nardelli, S. C.; da Silva Augusto, L.; Motta, M. C.; Girard-Dias, W.; Miranda, K.; Ulrich, P.; Jimenez, V.; Barquilla, A.; Navarro, M.; Docampo, R.; Schenkman, S. Target of rapamycin (TOR)-like 1 kinase is involved in the control of polyphosphate levels and acidocalcisome maintenance in Trypanosoma brucei J. Biol. Chem. 2010, 285, 24131-24140
28. Meng, F.; Zhu, X.; Li, Y.; Xie, J.; Wang, B.; Yao, J.; Wan, Y. Efficient copper-catalyzed direct amination of aryl halides using aqueous ammonia in water Eur. J. Org. Chem. 2010, 2010, 6149-6152
29. Hirumi, H.; Hirumi, K. Continuous cultivation of Trypanosoma brucei blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers J. Parasitol. 1989, 75, 985-989 (Pubitemid 20099178)
30. Bligh, E. G.; Dyer, W. J. A rapid method of total lipid extraction and purification Can. J. Biochem. Physiol. 1959, 37, 911-917
31. Richmond, G. S.; Gibellini, F.; Young, S. A.; Major, L.; Denton, H.; Lilley, A.; Smith, T. K. Lipidomic analysis of bloodstream and procyclic form Trypanosoma brucei Parasitology 2010, 137, 1357-1392