1,2,4-Oxadiazoles identified by virtual screening and their non-covalent inhibition of the human 20s proteasome

Current Medicinal Chemistry

Volumn 20, Issue 18, 2013, Pages 2351-2362

  Marechal X ^a   Genin, E ^b   Qin, L ^a   Sperandio, O ^c   Montes, M ^c   Basse, N ^a   Richy, N ^b   Miteva, M A ^c   Reboud Ravaux, M ^a   Vidal, J ^b   Villoutreix, B O ^c  

^a SORBONNE UNIVERSITÉ   (France)

^b Chimie et Photonique Moleculaires Rennes   (France)

^c INSERM   (France)

Author keywords

Chymotrypsin like subsite S5 binding; Cytotoxicity; Non covalent inhibitors; Oxadiazoles; Proteasome; Virtual screening

Indexed keywords

1,2,4 OXADIAZOLE DERIVATIVE; BORTEZOMIB; CALPAIN; CATHEPSIN B; CATHEPSIN B INHIBITOR; CHYMOTRYPSIN; LIGAND; PROTEASOME; PROTEASOME INHIBITOR; SALINOSPORAMIDE A;

ANTINEOPLASTIC ACTIVITY; ARTICLE; COMPUTER MODEL; CONTROLLED STUDY; CRYSTAL STRUCTURE; CYTOTOXICITY; DRUG BINDING; DRUG EFFECT; DRUG HALF LIFE; DRUG INHIBITION; DRUG SCREENING; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; FEMALE; HELA CELL; HUMAN; HUMAN CELL; IC 50; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOLECULAR MODEL; PROCESS OPTIMIZATION; STEREOCHEMISTRY;

CELL SURVIVAL; DRUG DESIGN; HEK293 CELLS; HELA CELLS; HUMANS; MOLECULAR DOCKING SIMULATION; OXADIAZOLES; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEASOME INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84877939655     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867311320180006     Document Type: Article

References (60)

1. Adams, J.; Kauffman, M. Development of the proteasome inhibitor Velcade (Bortezomib). Cancer Invest., 2004, 22 (2), 304-311.
2. Richardson, P. G.; Mitsiades, C.; Hideshima, T.; Anderson, K. C. Bortezomib: proteasome inhibition as an effective anticancer therapy. Annu. Rev. Med., 2006, 57, 33-47.
3. Genin, E.; Reboud-Ravaux, M.; Vidal, J. Proteasome inhibitors: recent advances and new perspectives in medicinal chemistry. Curr. Top. Med. Chem., 2010, 10 (3), 232-256.
4. O'Connor, O. A.; Stewart, A. K.; Vallone, M.; Molineaux, C. J.; Kunkel, L. A.; Gerecitano, J. F.; Orlowski, R. Z. A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin. Cancer Res., 2009, 15 (22), 7085-7091.
5. Moreau, P.; Richardson, P. G.; Cavo, M.; Orlowski, R. Z.; San Miguel, J. F.; Palumbo, A.; Harousseau, J.-L. Proteasome inhibitors in multiple myeloma: 10 years later. Blood, 2012, 120 (5), 947-959.
6. Potts, B. C.; Albitar, M. X.; Anderson, K. C.; Baritaki, S.; Berkers, C.; Bonavida, B.; Chandra, J.; Chauhan, D.; Cusack, J. C.; Fenical, W.; Ghobrial, I. M.; Groll, M.; Jensen, P. R.; Lam, K. S.; Lloyd, G. K.; McBride, W.; McConkey, D. J.; Miller, C. P.; Neuteboom, S. T. C.; Oki, Y.; Ovaa, H.; Pajonk, F.; Richardson, P. G.; Roccaro, A. M.; Sloss, C. M.; Spear, M. A.; Valashi, E.; Younes, A.; Palladino, M. A. Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr. Cancer Drug Targets, 2011, 11 (3), 254-284.
7. Kupperman, E.; Lee, E. C.; Cao, Y.; Bannerman, B.; Fitzgerald, M.; Berger, A.; Yu, J.; Yang, Y.; Hales, P.; Bruzzese, F.; Liu, J.; Blank, J.; Garcia, K.; Tsu, C.; Dick, L.; Fleming, P.; Yu, L.; Manfredi, M.; Rolfe, M.; Bolen, J. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res., 2010, 70 (5), 1970-1980.
8. Zhou, H.-J.; Aujay, M. A.; Bennett, M. K.; Dajee, M.; Demo, S. D.; Fang, Y.; Ho, M. N.; Jiang, J.; Kirk, C. J.; Laidig, G. J.; Lewis, E. R.; Lu, Y.; Muchamuel, T.; Parlati, F.; Ring, E.; Shenk, K. D.; Shields, J.; Shwonek, P. J.; Stanton, T.; Sun, C. M.; Sylvain, C.; Woo, T. M.; Yang, J. Design and Synthesis of an Orally Bioavailable and Selective Peptide Epoxyketone Proteasome Inhibitor (PR-047). J. Med. Chem., 2009, 52 (9), 3028-3038.
9. Piva, R.; Ruggeri, B.; Williams, M.; Costa, G.; Tamagno, I.; Ferrero, D.; Giai, V.; Coscia, M.; Peola, S.; Massaia, M.; Pezzoni, G.; Allievi, C.; Pescalli, N.; Cassin, M.; di Giovine, S.; Nicoli, P.; de Feudis, P.; Strepponi, I.; Roato, I.; Ferracini, R.; Bussolati, B.; Camussi, G.; Jones-Bolin, S.; Hunter, K.; Zhao, H.; Neri, A.; Palumbo, A.; Berkers, C.; Ovaa, H.; Bernareggi, A.; Inghirami, G. CEP-18770: a novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood, 2008, 111 (5), 2765-2775.
10. Meiners, S.; Ludwig, A.; Stangl, V.; Stangl, K. Proteasome inhibitors: Poisons and remedies. Med. Res. Rev., 2008, 28 (2), 309-327.
11. Bonuccelli, G.; Sotgia, F.; Capozza, F.; Gazzerro, E.; Minetti, C.; Lisanti, M. P. Localized treatment with a novel FDA-Approved proteasome inhibitor blocks the degradation of dystrophin and dystrophin-associated proteins in mdx mice. Cell Cycle, 2007, 6 (10), 1242-1248.
12. Schwartz, A. L.; Ciechanover, A. Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. Annu. Rev. Pharmacol. Toxicol., 2009, 49, 73-96.
13. Lin, G.; Li, D.; de Carvalho, L. P.; Deng, H.; Tao, H.; Vogt, G.; Wu, K.; Schneider, J.; Chidawanyika, T.; Warren, J. D.; Li, H.; Nathan, C. Inhibitors selective for mycobacterial versus human proteasomes. Nature, 2009, 461 (7264), 621-626.
14. Steverding, D.; Wang, X.; Potts, B. C.; Palladino, M. A. Trypanocidal activity of beta-lactone-gamma-lactam proteasome inhibitors. Planta Med., 2012, 78 (2), 131-134.
15. Lindenthal, C.; Weich, N.; Chia, Y. S.; Heussler, V.; Klinkert, M. Q. The proteasome inhibitor MLN-273 blocks exoerythrocytic and erythrocytic development of Plasmodium parasites. Parasitology, 2005, 131 (Pt 1), 37-44.
16. Li, H.; Ponder, E. L.; Verdoes, M.; Asbjornsdottir, K. H.; Deu, E.; Edgington, L. E.; Lee, J. T.; Kirk, C. J.; Demo, S. D.; Williamson, K. C.; Bogyo, M. Validation of the proteasome as a therapeutic target in Plasmodium using an epoxyketone inhibitor with parasitespecific toxicity. Chem. Biol., 2012, 19 (12), 1535-1545.
17. Groll, M.; Goetz, M.; Kaiser, M.; Weyher, E.; Moroder, L. TMC-95-based inhibitor design provides evidence for the catalytic versatility of the proteasome. Chem. Biol., 2006, 13 (6), 607-614.
18. Kaiser, M.; Groll, M.; Siciliano, C.; Assfalg-Machleidt, I.; Weyher, E.; Kohno, J.; Milbradt, A. G.; Renner, C.; Huber, R.; Moroder, L. Binding mode of TMC-95A analogues to eukaryotic 20S proteasome. ChemBioChem, 2004, 5 (9), 1256-1266.
19. Kaiser, M.; Milbradt, A. G.; Siciliano, C.; Assfalg-Machleidt, I.; Machleidt, W.; Groll, M.; Renner, C.; Moroder, L. TMC-95A analogues with endocyclic biphenyl ether group as proteasome inhibitors. Chem. Biodiversity, 2004, 1 (1), 161-173.
20. Kaiser, M.; Siciliano, C.; Assfalg-Machleidt, I.; Groll, M.; Milbradt, A. G.; Moroder, L. Synthesis of a TMC-95A Ketomethylene Analogue by Cyclization via Intramolecular Suzuki Coupling. Org. Lett., 2003, 5 (19), 3435-3437.
21. Kaiser, M.; Groll, M.; Renner, C.; Huber, R.; Moroder, L. The core structure of TMC-95A is a promising lead for reversible proteasome inhibition. Angew. Chem., Int. Ed., 2002, 41 (5), 780-783.
22. Lin, S.; Yang, Z.-Q.; Kwok, B. H. B.; Koldobskiy, M.; Crews, C. M.; Danishefsky, S. J. Total synthesis of TMC-95A and-B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR. J. Am. Chem. Soc., 2004, 126 (20), 6347-6355.
23. Basse, N.; Piguel, S.; Papapostolou, D.; Ferrier-Berthelot, A.; Richy, N.; Pagano, M.; Sarthou, P.; Sobczak-Thepot, J.; Reboud-Ravaux, M.; Vidal, J. Linear TMC-95-based proteasome inhibitors. J. Med. Chem., 2007, 50 (12), 2842-2850.
24. Groll, M.; Gallastegui, N.; Maréchal, X.; Le Ravalec, V.; Basse, N.; Richy, N.; Genin, E.; Huber, R.; Moroder, L.; Vidal, J.; Reboud-Ravaux, M. 20S Proteasome inhibition: designing noncovalent linear peptide mimics of the natural product TMC-95A. ChemMedChem, 2010, 1701-1705.
25. Maréchal, X.; Pujol, A.; Richy, N.; Genin, E.; Basse, N.; Reboud-Ravaux, M.; Vidal, J. Noncovalent inhibition of 20S proteasome by pegylated dimerized inhibitors. Eur. J. Med. Chem., 2012, 52, 322-327.
26. Koguchi, Y.; Kohno, J.; Nishio, M.; Takahashi, K.; Okuda, T.; Ohnuki, T.; Komatsubara, S. TMC-95A, B, C, and D, novel proteasome inhibitors produced by Apiospora montagnei Sacc. TC 1093. Taxonomy, production, isolation, and biological activities. J. Antibiot., 2000, 53 (2), 105-109.
27. Formicola, L.; Marechal, X.; Basse, N.; Bouvier-Durand, M.; Bonnet-Delpon, D.; Milcent, T.; Reboud-Ravaux, M.; Ongeri, S. Novel fluorinated pseudopeptides as proteasome inhibitors. Bioorg. Med. Chem. Lett., 2009, 19 (1), 83-86.
28. Furet, P.; Imbach, P.; Furst, P.; Lang, M.; Noorani, M.; Zimmermann, J.; Garcia-Echeverria, C. Modeling of the binding mode of a non-covalent inhibitor of the 20S proteasome. Application to structure-based analogue design. Bioorg. Med. Chem. Lett., 2001, 11 (10), 1321-1324.
29. Furet, P.; Imbach, P.; Noorani, M.; Koeppler, J.; Laumen, K.; Lang, M.; Guagnano, V.; Fuerst, P.; Roesel, J.; Zimmermann, J.; Garcia Echeverria, C. Entry into a new class of potent proteasome inhibitors having high antiproliferative activity by structure-based design. J. Med. Chem., 2004, 47 (20), 4810-4813.
30. Blackburn, C.; Gigstad, K. M.; Hales, P.; Garcia, K.; Jones, M.; Bruzzese, F. J.; Barrett, C.; Liu, J. X.; Soucy, T. A.; Sappal, D. S.; Bump, N.; Olhava, E. J.; Fleming, P.; Dick, L. R.; Tsu, C.; Sintchak, M. D.; Blank, J. L. Characterization of a new series of non-covalent proteasome inhibitors with exquisite potency and selectivity for the 20S beta 5-subunit. Biochem. J., 2010, 430, 461-476.
31. Blackburn, C.; Barrett, C.; Blank, J. L.; Bruzzese, F. J.; Bump, N.; Dick, L. R.; Fleming, P.; Garcia, K.; Hales, P.; Hu, Z. G.; Jones, M.; Liu, J. X.; Sappal, D. S.; Sintchak, M. D.; Tsu, C.; Gigstad, K. M. Optimization of a series of dipeptides with a P3 threonine residue as non-covalent inhibitors of the chymotrypsin-like activity of the human 20S proteasome. Bioorg. Med. Chem. Lett., 2010, 20 (22), 6581-6586.
32. Gallastegui, N.; Beck, P.; Arciniega, M.; Huber, R.; Hillebrand, S.; Groll, M. Hydroxyureas as Noncovalent Proteasome Inhibitors. Angew. Chem. Int. Ed., 2012, 51 (1), 247-249.
33. Basse, N.; Montes, M.; Marechal, X.; Qin, L.; Bouvier-Durand, M.; Genin, E.; Vidal, J.; Villoutreix, B. O.; Reboud-Ravaux, M. Novel organic proteasome inhibitors identified by virtual and in vitro screening. J. Med. Chem., 2010, 53 (1), 509-513.
34. Miteva, M. A.; Lee, W. H.; Montes, M. O.; Villoutreix, B. O. Fast structure-based virtual ligand screening combining FRED, DOCK, and Surflex. J. Med. Chem., 2005, 48 (19), 6012-6022.
35. Sauton, N.; Lagorce, D.; Villoutreix, B.; Miteva, M. MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening. BMC Bioinformatics, 2008, 9 (1), 184.
36. Jain, A. N. Surflex-Dock 2.1: Robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search. J. Comput. Aided Mol. Des., 2007, 21 (5), 281-306.
37. Unno, M.; Mizushima, T.; Morimoto, Y.; Tomisugi, Y.; Tanaka, K.; Yasuoka, N.; Tsukihara, T. The structure of the mammalian 20S proteasome at 2.75 A resolution. Structure, 2002, 10 (5), 609-618.
38. Lagorce, D.; Sperandio, O.; Galons, H.; Miteva, M.; Villoutreix, B. FAF-Drugs2: Free ADME/tox filtering tool to assist drug discovery and chemical biology projects. BMC Bioinformatics, 2008, 9 (1), 396.
39. Lipinski, C. A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods, 2000, 44 (1), 235-249.
40. Taboureau, O.; Baell, J. B.; Fernández-Recio, J.; Villoutreix, B. O. Established and emerging trends in computational drug discovery in the structural genomics era. Chem. Biol., 2012, 19 (1), 29-41.
41. Leite, T. B.; Gomes, D.; Miteva, M. A.; Chomilier, J.; Villoutreix, B. O.; Tuffery, P. Frog: a FRee Online druG 3D conformation generator. Nucleic Acids Res., 2007, 35 (Web Server issue), W568-72.
42. Lagorce, D.; Pencheva, T.; Villoutreix, B. O.; Miteva, M. A. DGAMMOS: a new tool to generate 3d conformation of small molecules using distance geometry and automated molecular mechanics optimization for in silico screening. BMC Chem. Biol., 2009, 9, 6.
43. von Grotthuss, M.; Pas, J.; Rychlewski, L. Ligand-Info, searching for similar small compounds using index profiles. Bioinformatics, 2003, 19 (8), 1041-1042.
44. Volkamer, A.; Kuhn, D.; Grombacher, T.; Rippmann, F.; Rarey, M. Combining global and local measures for structure-based druggability predictions. J.Chem. Inf. Model., 2012, 52 (2), 360-372.
45. Pérot, S.; Sperandio, O.; Miteva, M. A.; Camproux, A. C.; Villoutreix, B. O. Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery. Drug Discov. Today, 2010, 15 (15-16), 656-667.
46. Thomsen, R.; Christensen, M. H. MolDock: a new technique for high-Accuracy molecular docking. J. Med. Chem., 2006, 49 (11), 3315-3321.
47. Khanum, S. A.; Khanum, N. F.; Shashikanth, M. Synthesis and anti-inflammatory activity of 2-Aryloxy methyl oxazolines. Bioorg. Med. Chem. Lett., 2008, 18 (16), 4597-4601.
48. Bedford, C. D.; Howd, R. A.; Dailey, O. D.; Miller, A.; Nolen, H. W., III; Kenley, R. A.; Kern, J. R.; Winterle, J. S. Nonquaternary cholinesterase reactivators. 3. 3(5)-Substituted 1,2,4-oxadiazol-5(3)-Aldoximes and 1,2,4-oxadiazole-5(3)-thiocarbohydroximates as reactivators of organophosphonate-inhibited eel and human acetylcholinesterase in vitro. J. Med. Chem., 1986, 29 (11), 2174-2183.
49. Hamzé, A.; Hernandez, J.-F.; Fulcrand, P.; Martinez, J. Synthesis of various 3-substituted 1,2,4-oxadiazole-containing chiral 3-And-Amino acids from Fmoc-protected aspartic acid. J. Org. Chem., 2003, 68 (19), 7316-7321.
50. Flora, K. P.; van't Riet, B.; Wampler, G. L. Antitumor activity of amidoximes (hydroxyurea analogs) in murine tumor systems. Cancer Res., 1978, 38 (5), 1291-1295.
51. Koufaki, M.; Kiziridi, C.; Nikoloudaki, F.; Alexis, M. N. Design and synthesis of 1,2-dithiolane derivatives and evaluation of their neuroprotective activity. Bioorg. Med. Chem. Lett., 2007, 17 (15), 4223-4227.
52. Jochims, J. C. 1, 2, 4-Oxadiazoles. In Comprehensive Heterocyclic Chemistry II Katritzky, A. R.; Rees, C. W.; Scriven, E. V. F., Eds. Pergamon: 1996, 4, 179-228.
53. Hemming, K. 1, 2, 4-Oxadiazoles. In Science of Synthesis: Houben-Weyl Methods of Molecular Transformations, Storr, R. C.; Gilchrist, T. L. Eds. Thieme: 2004, 13, 127-184.
54. Kayukova, L. A. Synthesis of 1, 2, 4-oxadiazoles. Pharm. Chem. J., 2005, 39 (10), 539-547.
55. Stewart, W. E.; Siddall, T. H. Nuclear magnetic resonance studies of amides. Chem. Rev., 1970, 70 (5), 517-551.
56. Reich, H. J. WindNMR: dynamic NMR spectra for Windows. J. Chem. Educ., 1995, 72 (12), 1086.
57. Borissenko, L.; Groll, M. 20S proteasome and its inhibitors: Crystallographic knowledge for drug development. Chem. Rev., 2007, 107 (3), 687-717.
58. Boström, J.; Hogner, A.; Llinàs, A.; Wellner, E.; Plowright, A. T. Oxadiazoles in medicinal chemistry. J. Med. Chem., 2012, 55 (5), 1817-1830.
59. Rydzewski, R. M.; Burrill, L.; Mendonca, R.; Palmer, J. T.; Rice, M.; Tahilramani, R.; Bass, K. E.; Leung, L.; Gjerstad, E.; Janc, J. W.; Pan, L. Optimization of subsite binding to the 5 subunit of the human 20S proteasome using vinyl sulfones and 2-keto-1,3,4-oxadiazoles: syntheses and cellular properties of potent, selective proteasome inhibitors. J. Med. Chem., 2006, 49 (10), 2953-2968.
60. Groll, M.; Berkers, C. R.; Ploegh, H. L.; Ovaa, H. Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome. Structure, 2006, 14 (3), 451-456.