9- and 11-substituted 4-azapaullones are potent and selective inhibitors of African trypanosoma

European Journal of Medicinal Chemistry

Volumn 83, Issue , 2014, Pages 274-283

  Maiwald, Franziska ^a   Benítez, Diego ^b   Charquero, Diego ^b   Dar, Mahin Abad ^c   Erdmann, Hanna ^c   Preu, Lutz ^a   Koch, Oliver ^d   Hölscher, Christoph ^c   Loaëc, Nadège ^e   Meijer, Laurent ^e   Comini, Marcelo A ^b   Kunick, Conrad ^a  

^a TECHNICAL UNIVERSITY OF BRAUNSCHWEIG   (Germany)

^b INSTITUT PASTEUR DE MONTEVIDEO   (Uruguay)

^c RESEARCH CENTER BORSTEL   (Germany)

^d TU DORTMUND UNIVERSITY   (Germany)

^e Centre de Perharidy   (France)

Author keywords

Chalcones; Cinnamides; Human trypanosomiasis; Nagana; Paullones; Trypanosoma brucei brucei

Indexed keywords

11 (3 OXO 3 PHENYPROP 1 EN 1 YL) 7,12 DIHYDROPYRIDO [2',3',2,3]AZEPINO [4,5 B]INDOL 6(5H) ON; 3 (6 OXO 5,6,7,12 TETRAHYDROPYRIDO[2',3',2,3]AZEPINO[4,5 B]INDOL 11 YL) N PHENYLACRYLAMIDE; 4 AZAPAULLONE DERIVATIVE; ANTIPROTOZOAL AGENT; UNCLASSIFIED DRUG; 11 (3 OXO 3 PHENYLPROP 1 EN 1 YL) 7,12 DIHYDROPYRIDO[2',3':2,3]AZEPINO[4,5 B]INDOL 6(5H) ONE; 11 IODO 7,12 DIHYDROPYRIDO[2',3':2,3]AZEPINO[4,5 B]INDOL 6(5H) ONE; 2 AMINOPYRIDINE 3 CARBOXYLIC ACID ETHYL ESTER; 3 (6 OXO 5,6,7,12 TETRAHYDROPYRIDO[2',3':2,3]AZEPINO[4,5 B]INDOL 11 YL) N PHENYLACRYLAMIDE; 5 HYDROXY 8 OXO 8,9 DIHYDRO 7H PYRIDO[2,3 B]AZEPINE 6 CARBOXYLIC ACID ETHYL ESTER; 5 [2 (2 IODOPHENYL)HYDRAZONO] 6,7 DIHYDRO 5H PYRIDO[2,3 B]AZEPINE 8(9H) ONE; 6,7,8,9 TETRAHYDRO 5H PYRIDO[2,3 B]AZEPINE 5,8 DIONE; ANTITRYPANOSOMAL AGENT; PAULLONE DERIVATIVE; BENZAZEPINE DERIVATIVE; PAULLONE;

AFRICAN TRYPANOSOMIASIS; ANTIPROTOZOAL ACTIVITY; ARTICLE; HECK REACTION; NONHUMAN; POLYMERIZATION; SUBSTITUTION REACTION; TRYPANOSOMA BRUCEI; ANIMAL CELL; BONE MARROW DERIVED MACROPHAGE; CELL VIABILITY; CONFORMATIONAL TRANSITION; DRUG DESIGN; DRUG SCREENING; DRUG SYNTHESIS; EC50; FLOW CYTOMETRY; GROWTH INHIBITION; LEISHMANIA MAJOR; LIGAND BINDING; MOUSE; PROTON NUCLEAR MAGNETIC RESONANCE; ANIMAL; CELL LINE; CELL PROLIFERATION; CHEMISTRY; DRUG EFFECTS; HUMAN; MACROPHAGE; PARASITOLOGY; PHYSIOLOGY; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TRYPANOSOMA BRUCEI BRUCEI;

ANIMALS; BENZAZEPINES; CELL LINE; CELL PROLIFERATION; DRUG DESIGN; HUMANS; MACROPHAGES; MICE; STRUCTURE-ACTIVITY RELATIONSHIP; TRYPANOCIDAL AGENTS; TRYPANOSOMA BRUCEI BRUCEI; TRYPANOSOMIASIS, AFRICAN;

EID: 84903307583     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2014.06.020     Document Type: Article

References (56)

1. W.H.O Trypanosomiasis, Human African (Sleeping Sickness), Factsheet 259 2013 http://www.who.int/mediacentre/factsheets/fs259/en/
2. A. MacLeod, A. Tait, and C.M.R. Turner The population genetics of Trypanosoma brucei and the origin of human infectivity Phil. Trans. R. Soc. Lond. B B 356 2001 1035 1044
3. O. Balmer, J.S. Beadell, W. Gibson, and A. Caccone Phylogeography and taxonomy of Trypanosoma brucei PLoS Negl. Trop. Dis. 5 2011 e961
4. I. Goodhead, P. Capewell, J.W. Bailey, T. Beament, M. Chance, S. Kay, S. Forrester, A. MacLeod, M. Taylor, H. Noyes, and N. Hall Whole-genome sequencing of Trypanosoma brucei reveals introgression between subspecies that is associated with virulence mBio 4 2013 e00197-13
5. R.E. Symula, J.S. Beadell, M. Sistrom, K. Agbebakun, O. Balmer, W. Gibson, S. Aksoy, and A. Caccone Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistance PLoS Negl. Trop. Dis. 6 2012 e1728
6. H.V. Xong, L. Vanhamme, M. Chamekh, C.E. Chimfwembe, J. Van Den Abbeele, A. Pays, N. Van Meirvenne, R. Hamers, P. De Baetselier, and E. Pays A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense Cell 95 1998 839 846
7. P.H. Holmes, E. Katunguka-Rwakishaya, J.J. Bennison, G.J. Wassink, and J.J. Parkins Impact of nutrition on the pathophysiology of bovine trypanosomiasis Parasitology 120 Suppl 2000 S73 S85
8. R.C. Ezeokonkwo, I.O. Ezeh, C.N. Iheagwam, W.E. Agu, and R.I.S. Agbede Efficacy of Kelamidium in the prevention and treatment of Trypanosoma brucei brucei infection in albino rats Comp. Clin. Pathol. 22 2013 219 226
9. C. Gadelha, J.M. Holden, H.C. Allison, and M.C. Field Specializations in a successful parasite: what makes the bloodstream-form African trypanosome so deadly? Mol. Biochem. Parasitol. 179 2011 51 58
10. A.H. Fairlamb Chemotherapy of human African trypanosomiasis: current and future prospects Trends Parasitol. 19 2003 488 494
11. F.E. Graf, P. Ludin, T. Wenzler, M. Kaiser, R. Brun, P.P. Pyana, P. Büscher, H.P. de Koning, D. Horn, and P. Mäser Aquaporin 2 mutations in Trypanosoma brucei gambiense field isolates correlate with decreased susceptibility to pentamidine and melarsoprol PLoS Negl. Trop. Dis. 7 2013 e2475
12. M.L. Stewart, R.J. Burchmore, C. Clucas, C. Hertz-Fowler, K. Brooks, A. Tait, A. Macleod, C.M. Turner, H.P. De Koning, P.E. Wong, and M.P. Barrett Multiple genetic mechanisms lead to loss of functional TbAT1 expression in drug-resistant trypanosomes Eukaryot. Cell. 9 2010 336 343
13. A.C. Likeufack, R. Brun, A. Fomena, and P. Truc Comparison of the in vitro drug sensitivity of Trypanosoma brucei gambiense strains from West and Central Africa isolated in the periods 1960-1995 and 1999-2004 Acta Trop. 100 2006 11 16
14. N. Maina, K.J. Maina, P. Mäser, and R. Brun Genotypic and phenotypic characterization of Trypanosoma brucei gambiense isolates from Ibba, South Sudan, an area of high melarsoprol treatment failure rate Acta Trop. 104 2007 84 90
15. L.D.B. Kinabo Pharmacology of existing drugs for animal trypanosomiasis Acta Trop. 54 1993 169 183
16. V. Delespaux, D. Geysen, P. Van den Bossche, and S. Geerts Molecular tools for the rapid detection of drug resistance in animal trypanosomes Trends Parasitol. 24 2008 236 242
17. Diseases, treatment, therapy H. Mehlhorn Enzyclopedic Reference of Parasitology 2 ed. 2001 Springer-Verlag Berlin 178 180
18. E.O. Mungube, H.S. Vitouley, E. Allegye-Cudjoe, O. Diall, Z. Boucoum, B. Diarra, Y. Sanogo, T. Randolph, B. Bauer, K.H. Zessin, and P.H. Clausen Detection of multiple drug-resistant Trypanosoma congolense populations in village cattle of south-east Mali Parasit. Vectors 5 2012 155
19. C. Reichwald, O. Shimony, U. Dunkel, N. Sacerdoti-Sierra, C.L. Jaffe, and C. Kunick 2-(3-Aryl-3-oxopropen-1-yl)-9-tert-butyl-paullones: a new antileishmanial chemotype J. Med. Chem. 51 2008 659 665
20. J. Ryczak, M. Papini, A. Lader, A. Nasereddin, D. Kopelyanskiy, L. Preu, C.L. Jaffe, and C. Kunick 2-Arylpaullones are selective antitrypanosomal agents Eur. J. Med. Chem. 64 2013 396 400
21. C.F. McGrath, N. Pattabiraman, G.E. Kellogg, T. Lemcke, C. Kunick, E.A. Sausville, D.W. Zaharevitz, and R. Gussio Homology model of the CDK1/cyclin B complex J. Biomol. Struct. Dyn. 22 2005 493 502
22. T. Pies, K.-J. Schaper, M. Leost, D.W. Zaharevitz, R. Gussio, L. Meijer, and C. Kunick CDK1-inhibitory activity of paullones depends on electronic properties of 9-substituents Arch. Pharm. Pharm. Med. Chem. 337 2004 486 492
23. N. Tolle, and C. Kunick Paullones as inhibitors of protein kinases Curr. Top. Med. Chem. 11 2011 1320 1332
24. K. Wieking, M. Knockaert, M. Leost, D.W. Zaharevitz, L. Meijer, and C. Kunick Synthesis of paullones with aminoalkyl side chains Arch. Pharm. Pharm. Med. Chem. 335 2002 311 317
25. X. Xie, T. Lemcke, R. Gussio, D.W. Zaharevitz, M. Leost, L. Meijer, and C. Kunick Epoxide-containing side chains enhance antiproliferative activity of paullones Eur. J. Med. Chem. 40 2005 655 661
26. C. Kunick, K. Lauenroth, K. Wieking, X. Xie, C. Schultz, R. Gussio, D. Zaharevitz, M. Leost, L. Meijer, A. Weber, F.S. Jorgensen, and T. Lemcke Evaluation and comparison of 3D-QSAR CoMSIA models for CDK1, CDK5, and GSK-3 inhibition by paullones J. Med. Chem. 47 2004 22 36
27. C. Kunick, K. Lauenroth, M. Leost, L. Meijer, and T. Lemcke 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 Bioorg. Med. Chem. Lett. 14 2004 413 416
28. C. Reichwald, O. Shimony, N. Sacerdoti-Sierra, C.L. Jaffe, and C. Kunick A new Heck reaction modification using ketone Mannich bases as enone precursors: parallel synthesis of anti-leishmanial chalcones Bioorg. Med. Chem. Lett. 18 2008 1985 1989
29. L. Flohé The trypanothione system and the opportunities it offers to create drugs for the neglected kinetoplast diseases Biotechnol. Adv. 30 2012 294 301
30. L.S. Torrie, S. Wyllie, D. Spinks, S.L. Oza, S. Thompson, J.R. Harrison, I.H. Gilbert, P.G. Wyatt, A.H. Fairlamb, and J.A. Frearson Chemical validation of trypanothione synthetase: a potential drug target for human trypanosomiasis J. Biol. Chem. 284 2009 36137 36145
31. M.A. Comini, S.A. Guerrero, S. Haile, U. Menge, H. Lünsdorf, and L. Flohé Validation of Trypanosoma brucei trypanothione synthetase as drug target Free Radic. Biol. Med. 36 2004 1289 1302
32. L. Flohé The trypanothione system and its implications in the therapy of trypanosomatid diseases Int. J. Med. Microbiol. 302 2012 216 220
33. M.A. Comini, U. Menge, J. Wissing, and L. Flohé Trypanothione synthesis in crithidia revisited J. Biol. Chem. 280 2005 6850 6860
34. P.K. Fyfe, S.L. Oza, A.H. Fairlamb, and W.N. Hunter Leishmania trypanothione synthetase-amidase structure reveals a basis for regulation of conflicting synthetic and hydrolytic activities J. Biol. Chem. 283 2008 17672 17680
35. O. Koch, D. Cappel, M. Nocker, T. Jäger, L. Flohé, C. Sotriffer, and P.M. Selzer Molecular dynamics reveal binding mode of glutathionylspermidine by trypanothione synthetase PLoS One 8 2013 e56788
36. S. Zimmermann, M. Oufir, A. Leroux, R. Krauth-Siegel, K. Becker, M. Kaiser, R. Brun, M. Hamburger, and M. Adams Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei Bioorg. Med. Chem. 21 2013 7202 7209
37. M.D. Urbaniak Casein kinase 1 isoform 2 is essential for bloodstream form Trypanosoma brucei Mol. Biochem. Parasitol. 166 2009 183 185
38. A.-M. Egert-Schmidt, J. Dreher, U. Dunkel, S. Kohfeld, L. Preu, H. Weber, J.E. Ehlert, B. Mutschler, F. Totzke, C. Schächtele, M.H.G. Kubbutat, K. Baumann, and C. Kunick Identification of 2-anilino-9-methoxy-5,7-dihydro-6H- pyrimido[5,4-d][1]benz¬azepin-6-ones as dual PLK1/VEGF-R2 kinase inhibitor chemotypes by structure-based lead generation J. Med. Chem. 53 2010 2433 2442
39. F.F. Blicke The Mannich reaction Org. React. 1 1942 303 341
40. J. Eriksson, O. Åberg, and B. Långström Synthesis of [11C]/[13C]acrylamides by palladium-mediated carbonylation Eur. J. Org. Chem. 2007 2007 455 461
41. N. Kuhnert, and A. Le-Gresley Synthesis and capsule formation of upper rim substituted tetra-acrylamido calix[4]arenes Org. Biomol. Chem. 3 2005 2175 2182
42. H.H. Fox Synthetic tuberculostats. II. Amino- and hydroxypyridine carboxylic acid derivatives J. Org. Chem. 17 1952 547 554
43. S.L. Oza, M.R. Ariyanayagam, N. Aitcheson, and A.H. Fairlamb Properties of trypanothione synthetase from Trypanosoma brucei Mol. Biochem. Parasitol. 131 2003 25 33
44. R.L. Krauth-Siegel, and M. Comini Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism Biochim. Biophys. Acta 1780 2008 1236 1248
45. M.C. Taylor, H. Kaur, B. Blessington, J.M. Kelly, and S.R. Wilkinson Validation of spermidine synthase as a drug target in African Trypanosomes Biochem. J. 409 2008 563 569
46. L. Flohé In search of trypanocidal drugs P.M. Selzer, Drug Discovery in Infectious Diseases: From Molecular Targets to Drug Candidates 2009 Wiley-VCH Weinheim 211 226
47. S. Biebinger, L.E. Wirtz, P. Lorenz, and C. Clayton Vectors for inducible expression of toxic gene products in bloodstream and procyclic Trypanosoma brucei Mol. Biochem. Parasitol. 85 1997 99 112
48. H. Hirumi, and K. Hirumi Continuous cultivation of Trypanosoma brucei blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers J. Parasitol. 75 1989 985 989
49. K. Bettayeb, N. Oumata, A. Echalier, Y. Ferandin, J.A. Endicott, H. Galons, and L. Meijer CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases Oncogene 27 2008 5797 5807
50. T. Tahtouh, J.M. Elkins, P. Filippakopoulos, M. Soundararajan, G. Burgy, E. Durieu, C. Cochet, R.S. Schmid, D.C. Lo, F. Delhommel, A.E. Oberholzer, L.H. Pearl, F. Carreaux, J.P. Bazureau, S. Knapp, and L. Meijer Selectivity, cocrystal structures and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B J. Med. Chem. 55 2012 9312 9330
51. A. Primot, B. Baratte, M. Gompel, A. Borgne, S. Liabeuf, J.L. Romette, F. Costantini, and L. Meijer Purification of GSK-3 by affinity chromatography on immobilised axin Protein Expr. Purif. 20 2000 394 404
52. J. Reinhardt, Y. Ferandin, and L. Meijer Purification of CK1 by affinity chromatography on immobilised axin Protein Expr. Purif. 54 2007 101 109
53. C. Hölscher, G. Köhler, U. Müller, H. Mossmann, G.A. Schaub, and F. Brombacher Defective nitric oxide effector functions lead to extreme susceptibility of Trypanosoma cruzi-infected mice deficient in gamma interferon receptor or inducible nitric oxide synthase Infect. Immun. 66 1998 1208 1215
54. Molecular Operating Environment (MOE), 2013.08; Chemical Computing Group Inc., 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7, 2013.
55. G. Jones, P. Willett, R.C. Glen, A.R. Leach, and R. Taylor Development and validation of a genetic algorithm for flexible docking J. Mol. Biol. 267 1997 727 748
56. J.W. Liebeschuetz, J.C. Cole, and O. Korb Pose prediction and virtual screening performance of GOLD scoring functions in a standardized test J. Comput. Aided Mol. Des. 26 2012 737 748