Several human cyclin-dependent kinase inhibitors, structurally related to roscovitine, as new anti-malarial agents

Molecules

Volumn 19, Issue 9, 2014, Pages 15237-15257

  Houzé, Sandrine ^a   Hoang, Nha Thu ^b   Lozach, Olivier ^c   Le Bras, Jacques ^a   Meijer, Laurent ^c,d   Galons, Hervé ^d,e   Demange, Luc ^b,f  

^a CNR du Paludisme   (France)

^b UNIVERSITÉ PARIS DESCARTES   (France)

^c CNRS   (France)

^d Centre de Perharidy   (France)

^e Laboratoire de Pharmacochimie   (France)

^f UNIVERSITÉ DE NICE SOPHIA ANTIPOLIS   (France)

Author keywords

2 6 9 trisubstituted purines; Buchwald Hartwig amination; Cyclin dependent kinases CDKs; PfCDKs; Plasmodium falciparum; Roscovitine

Indexed keywords

ANTIMALARIAL AGENT; CYCLIN DEPENDENT KINASE; PROTEIN KINASE INHIBITOR; PURINE DERIVATIVE; ROSCOVITINE;

ANTAGONISTS AND INHIBITORS; CHEMISTRY; ELECTROSPRAY MASS SPECTROMETRY; HUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY;

ANTIMALARIALS; CYCLIN-DEPENDENT KINASES; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; PROTEIN KINASE INHIBITORS; PURINES; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION;

EID: 84907432562     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules190915237     Document Type: Article

References (76)

1. World Malaria Report 2013; WHO Press: Geneva, Switzerland, 2013. Available online: http://www.who.int (accessed on 22 September 2014
2. Robert, V.; Boudin, C. Biologie de la transmission homme-moustique du plasmodium. Bull. Soc. Pathol. Exot. 2003, 96, 6-20.
3. Park, D.J.; Lukens, A.K.; Neafsey, D.E.; Schaffner, S.F.; Chang, H.-H.; Valim, C.; Ribacke, U.; van Tyne, D.; Galinsky, K.; Galligan, M.; et al. Sequence-Based association and selection scans identify drug resistance loci in the plasmodium falciparum malaria parasite. Proc. Natl. Acad. Sci. USA 2012, 109, 13052-13057.
4. Fairhurst, R.M.; Nayyar, G.M.; Breman, J.G.; Hallett, R.; Vennerstrom, J.L.; Duong, S.; Ringwald, P; Wellems, T.E.; Plowe, C.V.; Dondorp, A.M. Artemisinin-resistant malaria: Research challenges, opportunities, and public health implications. Am. J. Trop. Med. Hyg. 2012, 87, 231-241.
5. Wittlin, S.; Ekland, E.; Craft, J.C.; Lotharius, J.; Bathurst, I.; Fidock, D.A.; Fernandes, P. In vitro and in vivo activity of solithromycin (CEM-101) against plasmodium species. Antimicrob. Agents Chemother. 2012, 56, 703-707.
6. Aureggi, V.; Ehmke, V.; Wieland, J.; Schweizer, W.B.; Bernet, B.; Bur, D.; Meyer, S.; Rottmann, M.; Freymond, C.; Brun, R.; et al. Potent inhibitors of malarial aspartic proteases, the plasmepsins, by hydroformylation of substituted 7-azanorbornenes. Chem. Eur. J. 2012, 19, 155-164.
7. Rodrigues, T.; Lopes, F.; Moreira, R. Inhibitors of the mitochondrial electron transport chain and de novo pyrimidine biosynthesis as antimalarials: the present status. Curr. Med. Chem. 2010, 17, 926-956.
8. Rotella, D.P. Recent results in protein kinase inhibition for tropical diseases. Bioorg. Med. Chem. Lett. 2012, 22, 6788-6793.
9. Doerig, C. Protein kinases as targets for anti-parasitic chemotherapy. Biochim. Biophys. Acta 2004, 1697, 155-168.
10. Doerig, C.; Billker, O.; Pratt, D.; Endicott, J. Protein kinases as targets for antimalarial intervention: Kinomics, structure-based design, transmission-blockade, and targeting host cell enzymes. Biochim. Biophys. Acta 2005, 1754, 132-150.
11. Doerig, C.; Meijer, L. Antimalarial drug discovery: Targeting protein kinases. Expert Opin. Ther. Targets 2007, 11, 279-290.
12. Noguchi, Y.; Yasuda, Y.; Tashiro, M.; Kataoka, T.; Kitamura, Y.; Kandeel, M.; Kitade, Y. Synthesis of carbocyclic pyrimidine nucleosides and their inhibitory activities against Plasmodium falciparum thymidylate kinase. Parasitol. Int. 2013, 62, 368-371.
13. Taylor, H.M.; McRobert, L.; Grainger, M.; Sicard, A.; Dluzewski, A.R.; Hopp, C.S.; Holder, A.A.; Baker, D.A. The malaria parasite cyclic GMP-dependent protein kinase plays a central role in blood-stage schizogony. Eukaryot. Cell 2010, 9, 37-45.
14. Chapman, T.M.; Osborne, S.A.; Bouloc, N.; Large, J.M.; Wallace, C.; Birchall, K.; Ansell, K.H.; Jones, H.M.; Taylor, D.; Clough, B.; et al. Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1). Bioorg. Med. Chem. Lett. 2013, 23, 3064-3069.
15. Chapman, T.M.; Osborne, S.A.; Wallace, C.; Birchall, K.; Bouloc, N.; Jones, H.M.; Ansell, K.H.; Taylor, D.L.; Clough, B.; Green, J.L.; et al. Optimization of an imidazopyridazine series of inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1). J. Med. Chem. 2014, 57, 3570-3587.
16. Nag, S.; Chouhan, D.K.; Balaji, S.N.; Chakraborty, A.; Lhouvum, K.; Bal, C.; Sharon, A.; Trivedi, V. Comprehensive screening of heterocyclic compound libraries to identify novel inhibitors for PfRIO-2 kinase through docking and substrate competition studies. Med. Chem. Res. 2013, 22, 4737-4744.
17. Malumbres, M.; Barbacid, M. Mammalian cyclin-dependent kinases. Trends Biochem. Sci. 2005, 30, 630-641.
18. Malumbres, M.; Harlow, E.; Hunt, T.; Hunter, T.; Lahti, J.M.; Manning, G.; Morgan, D.O.; Tsai, L.-H.; Wolgemuth, D.J. Cyclind-Dependent kinases: A family portrait. Nat. Cell Biol. 2009, 11, 1275-1276.
19. Carassou, P.; Meijer, L.; le Moulec, S.; Aoun, J.; Bengrine-Lefevre, L. Cell-Cycle and molecular targets: CDK inhibition. Bull. Cancer 2012, 99, 163-171.
20. Malumbres, M.; Barbacid, M. Cell cycle, CDKs and cancer: A changing paradigm. Nat. Rev. Cancer 2009, 9, 153-166.
21. Meijer, L. The cell division cycle and its regulation. Bull. Cancer 2006, 93, 41-53.
22. Borgne, A.; Golsteyn, R.M. The role of cyclin-dependent kinases in apoptosis. Prog. Cell Cycle Res. 2003, 5, 453-459.
23. Garriga, J.; Grana, X. Cellular control of gene expression by T-type cyclin/CDK9 complexes. Gene 2004, 337, 15-23.
24. Cruz, J.; Tsai, L.H. CDK5 deregulation in the pathogenesis of Alzheimer?s disease. Trends Mol. Med. 2004, 10, 452-458.
25. Sadleir, K.R.; Vassar, R. CDK5 protein inhibition and A?42 increase BACE1 protein level in primary neurons by a post-transcriptional mechanism: Implications of CDK5 as a therapeutic target for Alzheimer disease. J. Biol. Chem. 2012, 287, 7224-7235.
26. Kitani, K.; Oguma, S.; Nishiki, T.-I.; Ohmori, I.; Galons, H.; Matsui, H.; Meijer, L.; Tomizawa, K. A CDK5 inhibitor enhances the induction of insulinsecretion by exendin-4 both in vitro and in vivo. J. Physiol. Sci. 2007, 54, 235-239.
27. Knockaert, M.; Greengard, P.; Meijer, L. Pharmacological inhibitors of cyclin dependent kinases. Trends Pharmacol. Sci. 2002, 23, 417-425.
28. Graeser, R.; Wernli, B.; Franklin, R.M.; Kappes, B. Plasmodium falciparum protein kinase 5 and the malarial nuclear division cycles. Mol. Biochem. Parasitol. 1996, 82, 37-49.
29. Bracchi-Ricard, V.; Barik, S.; Delvecchio, C.; Doerig, C.; Chakrabarti, R.; Chakrabarti, D. PfPK6, a novel cyclin-dependent kinase/mitogen-activated protein kinase-related protein kinse from Plasmodium falciparum. Biochem. J. 2000, 347, 255-263.
30. Li, J.L.; Robson, K.J.; Chen, J.L.; Targett, G.A.; Baker, D.A. Pfmrk, a MO15-related protein kinase from Plasmodium falciparum. Gene cloning, sequence, stage-specific expression and chromosome localization. Eur. J. Biochem. 1996, 241, 805-813.
31. Li, Z.; le Roch, J.A.; Geyer, C.L.; Woodard, S.T.; Prigge, J.; Koh, C.; Doerig, N.C. Waters, influence of human p16(INK4) and p21 (CIP) on the in vitro activity of recombinant Plasmodium falciparum cyclin-dependent protein kinases. Biochem. Biophys. Res. Commun. 2001, 288, 1207-1211.
32. Le Roch, K.; Sestier, C.; Dorin, D.; Waters, N.; Kappes, B.;Chakrabarti, D.; Meijer, L.; Doerig, C. Activation of a Plasmodium falciparum cdc-2related kinase by heterogenous p25 and cyclin H: Functional characterization of a P. falciparum cyclin homologue. J. Biol. Chem. 2000, 275, 8952-8958.
33. Wiese, M. Leishmania MAP kinases-Familiar proteins in an unusual context. Int. J. Parasitol. 2007, 37, 1053-1062.
34. Woodward, C.L.; Li, Z.; Kathcart, A.K.; Terrell, J.; Gerena, L.; Lopez-Sanchez, M.; Kyle, D.E.; Bhattacharjee, A.K.; Nichols, D.A.; Ellis, W.; et al. Oxindole-Based compounds are selective inhibitors of Plasmodium falciparum cyclin dependent protein kinases. J. Med. Chem. 2003, 46, 3877-3882.
35. Holton, S.; Merckx, A.; Burgess, D.; Doerig, C.; Noble, M. Structures of P. falciparum PfPK5 test the CDK regulation paradigm and suggest mechanisms of small molecule inhibition. Structure 2003, 11, 1329-1337.
36. Bhattacharjee, A.K.; Geyer, J.A.; Woodard, C.L.; Kathcart, A.K.; Nichols, D.A.; Prigge, S.T.; Li, Z.; Mott, B.T.; Waters, N.C. A three-dimensional in silico pharmacophore model inhibition of Plasmodium falciparum cyclin-dependent kinases and discovery of different classes of novel Pfmrk specific inhibitors. J. Med. Chem. 2004, 47, 5418-5426.
37. Geyer, J.A.; Keenan, S.M.; Woodard, C.L.; Thompson, P.A.; Gerena, L.; Nichols, D.A.; Gutteridge, C.E.; Waters, N.C. Selective inhibition of Pfmrk, a Plasmodium falciparum CDK, by antimalarial 1,3-diaryl-2-propenone. Bioorg. Med. Chem. Lett. 2009, 19, 1982-1985.
38. Woodard, C.L.; Keenan, S.M.; Gerena, L.; Welsh, W.J.; Geyer, J.A.; Waters, N.C. Evaluation of broad spectrum protein kinase inhibitors to probe the architecture of the malarial cyclin dependent protein kinase Pfmrk. Bioorg. Med. Chem. Lett. 2007, 17, 4961-4966.
39. Legraverend, M.; Grierson, D.S. The purines: Potent and versatile small molecule inhibitors and modulators of key biological targets. Bioorg. Med. Chem. 2006, 14, 3987-4006.
40. Haystead, T.A. The purinome, a complex mix of drug and toxicity targets. Curr. Top. Med. Chem. 2006, 6, 1117-1127.
41. Meijer, L.; Raymond, E. Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials. Acc. Chem. Res. 2003, 36, 417-425.
42. Bach, S.; Knockaert, M.; Reinhardt, J.; Lozach, O.; Schmitt, S.; Baratte, B.; Koken, M.; Coburn, S.P.; Tang, L.; Jiang, T.; et al. Roscovitine targets, protein kinases and pyridoxal kinase. J. Biol. Chem. 2005, 280, 31208-31219.
43. Brain, J.; Plater, L.; Elliott, M.; Shpiro, N.; Hastie, C.J.; Mac Lauchlan, H.; Klevernic, I.; Arthur, J.S.; Alessi, D.R.; Cohen, P. The selectivity of protein kinase inhibitors: A further update. Biochem. J. 2007, 408, 297-315.
44. Oumata, N.; Bettayeb, K.; Ferandin, Y.; Demange, L.; Lopez-Giral, A.; Goddard, M.-L.; Myriabthopoulos, V.; Mikros, E.; Flajolet, M.; Greengard, P.; et al. Roscovitine-derived, dual-specificity inhibitors of cyclin-dependent kinases and casein kinases 1. J. Med. Chem. 2008, 51, 5229-5242.
45. Demange, L.; Nait Abdellah, F.; Lozach, O.; Ferandin, Y.; Gresh, N.; Meijer, L.; Galons, H. Potent inhibitors of CDK5 derived from roscovitine: Synthesis, biological evaluation and molecular modelling. Bioorg. Med. Chem. Lett. 2013, 23, 125-131.
46. Demange, L.; Lozach, O.; Ferandin, Y.; Hoang, N.-T.; Meijer, L.; Galons, H. Synthesis and evaluation of new potent inhibitors of CK1 and CDK5, two kinases involved in Alzheimer?s disease. Med. Chem. Res. 2013, 22, 3247-3258.
47. Demange, L.; Oumata, N.; Quinton, J.; Bouaziz, S.; Lozach, O.; Meijer, L.; Galons, H. Synthesis of 6-pyridylaminopurines. Heterocycles 2008, 75, 1735-1743.
48. Surry, D.S.; Buchwald, S.L. Selective palladium-catalyzed arylation of ammonia: Synthesis of anilines as well as symmetrical and unsymmetrical di-and triarylamines. J. Am. Chem. Soc. 2007, 129, 10354-10355.
49. Tang, L.; Li, M.-H.; Cao, P.; Wang, F.; Chang, W.-R.; Bach, S.; Reinhardt, J.; Ferandin, Y.; Galons, H.; Wan, Y.; et al. Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives. J. Biol. Chem. 2005, 280, 31220-31229.
50. Otyepka, M.; Krystof, V.; Havlicek, L.; Siglerova, V.; Strnad, M.; Koca, J. Docking-Based development of purine-like inhibitors of cyclin-dependent kinase-2. J. Med. Chem. 2000, 43, 2506-2513.
51. Dhariwala, F.A.; Rajadhyaksha, M.S. An unusual member of the Cdk family: Cdk5. Cell. Mol. Neurobiol. 2008, 28, 351-369.
52. Utreras, E.; Futatsugi, A.; Rudrabhatla, P.; Keller, J.; Iadarola, M.J.; Pant, H.C.; Kulkarni, A.B. Tumor necrosis factor-? regulates cyclin-dependent inase 5 activity during pain signaling through transcriptional activation of p35. J. Biol. Chem. 2009, 284, 2275-2284.
53. Wei, F.-Y.; Nagashima, K.; Ohshima, T.; Saheki, Y.; Lu, Y.-F.; Matsushita, M.; Yamada, Y.; Mikoshiba, K.; Seino, Y.; Matsui, H.; et al. Cdk5-Dependent regulation of glucose-stimulated insulin secretion. Nat. Med. 2005, 11, 1104-1108.
54. Heathcore, D.A.; Patel, H.; Kroll, S.H.B.; Hazel, P.; Periyasamy, M.; Alikian, M.; Kanneganti, S.K.; Jogelakar, A.S.; Schreiper, B.; Barbazanges, M.; et al. A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2 and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration. J. Med. Chem. 2010, 53, 8508-8522.
55. Laha, J.K.; Zhang, X.; Qiao, L.; Liu, M.; Chatterjee, S.; Robinson, S.; Kosic, K.S.; Cuny, G.D. Structure-activity relationship study of 2,4-diaminothiazoles as Cdk5/p25 kinase inhibitors. Bioorg. Med. Chem. Lett. 2011, 21, 2098-2101.
56. Shiradkar, M.; Thomas, J.; Kanase, V.; Dighe, R. Studying synergism of methyl linked cyclohexyl thiophenes with triazole: Synthesis and their cdk5/p25 inhibition activity. Eur. J. Med. Chem. 2011, 46, 2066-2074.
57. Flajolet, M.; He, G.; Heiman, M.; Lin, A.; Nairn, A.C.; Greengard, P. Regulation of Alzheimer?s disease amyloid-beta formation by casein kinase I. Proc. Natl. Acad. Sci. USA 2007, 104, 4159-4164.
58. Meijer, L.; Thunnissen, A.M.; White, A.M.; Garnier, M.; Nikolic, M.; Tsai, L.H.; Walter, J.; Cleverley, K.E.; Salinas, P.C.; Wu, Y.Z.; et al. Inhibition of the cyclin dependent kinases, GSK-3beta and CK1 by hymenialdisine, a marine sponge constituent. Chem. Biol. 2000, 7, 51-63.
59. Perez, D.I.; Gil, C.; Martinez, A. Proteine kinases CK1 and CK2 as new targets for neurodegenerative diseases. Med. Res. Rev. 2011, 31, 924-954.
60. Wegiel, J.; Gong, C.X.; Hwang, Y.W. The role of DYRK 1A in neurodegenerative diseases. FEBS J. 2011, 278, 239-245.
61. Smith, B.; Medda, F.; Gokhale, V.; Dunckley, T.; Hulme, C. Recent advances in the design, synthesis, and biological evaluation of selective DYRK1A inhibitors: A new avenue for a disease modifying treatment of Alzheimer?s. ACS Chem. Neurosci. 2012, 3, 857-872.
62. Dedbab, M.; Carreaux, F.; Renault, S.; Soundararajan, M.; Fedorov, O.; Filippakopoulos, P.; Lozach, O.; Babault, L.; Tahtouh, T.; Baratte, B.; et al. Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B. Modulation of alternative pre-RNA splicing. J. Med. Chem. 2011, 54, 4172-4186.
63. Tahtouh, T.; Elkins, J.M.; Filippakopoulos, P.; Soundarararjan, M.; Burgy, G.; Durieu, E.; Cochet, C.; Schmid, R.S.; Lo, D.C.; Delhommel, F.; et al. Selectivity, co-crystal structures and neuroprotective properties of Leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid Leucettamine B. J. Med. Chem. 2012, 55, 9312-9330.
64. Neagoie, C.; Vedrenne, E.; Buron, F.; Mérour, J.Y.; Rosca, S.; Bourg, S.; Lozach, O.; Meijer, L.; Baldeytou, B.; Lansiaux, A.; et al. Synthesis of chromeno[3,4-b]indoles as lamellarin D analogs: A novel DYRK 1A inhibitor class. Eur. J. Med. Chem. 2012, 49, 379-396.
65. Beniddir, M.A.; le Borgne, E.; Iorga, B.I.; Loaec, N.; Lozach, O.; Meijer, L.; Awang, K.; Litaudon, M. Acridone alkaloids from glycosmis chlorosperma as DYRK1A inhibitors. J. Nat. Prod. 2014, 77, 1117-1122.
66. Dehbi, O.; Tikad, A.; Bourg, S.; Bonnet, P.; Lozach, O.; Meijer, L.; Aadil, M.; Akssira, M.; Guillaumet, G.; Routier, S. Synthesis and optimization of an original V-shaped collection of 4-7-disubstituted pyrido[3,2-d]pyrimidines as CDK5 and DYRK1A inhibitors. Eur. J. Med. Chem. 2014, 80, 352-363.
67. Pan, Y.; Wang, Y.; Bryant, S.H. Pharmacophore and 3D-QSAR characterization of 6-arylquinazolin-4-amines as cdc-2 like kinase 4 (Clk4) and dual specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) inhibitors. J. Chem. Inf. Model. 2013, 53, 938-947.
68. Elagawany, M.; Ibrahim, M.A.; Ali Ahmed, H.E.; El-Etrawy, A.S.; Ghiaty, A.; Abdel-Samii, Z.K.; El-Feky, S.A.; Bajorath, J. Design, synthesis, and molecular modeling of pyridazinone and phthalazinone derivatives as protein kinases inhibitors. Bioorg. Med. Chem. Lett. 2013, 23, 2007-2013.
69. Desjardins, R.E.; Canfield, C.J.; Haynes, J.D.; Chulay, J.D. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob. Agents Chemother. 1979, 16, 710-718.
70. Harmse, L.; van Zyl, R.; Gray, N.; Schultz, P.; Leclerc, S.; Meijer, L.; Doerig, C.; Havlik, I. Structure-Activity relationships and inhibitory effects of various purine derivatives on the in vitro growth of Plasmoduim falciparum. Biochem. Pharmacol. 2001, 62, 341-348.
71. Too, K.; Brown, D.M.; Bongard, E.; Yardley, V.; Vivas, L.; Loakes, D. Anti-Malarial activity of N6-modified purine analogues. Bioorg. Med. Chem. 2007, 15, 5551-5562.
72. Legraverend, M.; Ludwig, O.; Bisagni, E.; Leclerc, S.; Meijer, L.; Giocanti, N.; Sadri, R.; Favaulon, V. Synthesis and in vitro evaluation of novel 2,6,9-trisubstituted purines acting as cyclin-dependent kinase inhibitors. Bioorg. Med. Chem. 1999, 7, 1281-1293.
73. Bettayeb, K.; Oumata, N.; Echalier, A.; Ferandin, Y.; Endicott, J.; Galons, H.; Meijer, L. CR8 a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. Oncogene 2008, 27, 5797-5807.
74. Reinhardt, J.; Ferandin, Y.; Meijer, L. Purification of GSK-3 by affinity chromatography on immobilized axin. Protein Expres. Purif. 2000, 20, 394-404.
75. Kaddouri, H.; Nakache, S.; Houzé, S.; Mentré, F.; le Bras, J. Drug susceptibility of Plasmodium falciparum clinical isolates from africa using plasmodium lactate dehydrogenase immunodetection assay and inhibitory emax model for precise IC50 measurement. Antimicrob. Agents Chemother. 2006, 50, 3343-3349.
76. ICEstimator Version 1.2. Available online: http://www.antimalarial-icestimator.net (accessed on 22 September 2014).