New potent acetylcholinesterase inhibitors in the tetracyclic triterpene series

Journal of Medicinal Chemistry

Volumn 50, Issue 22, 2007, Pages 5311-5323

  Sauvaître, Thibault ^a   Barlier, Mireille ^a   Herlem, Denyse ^a   Gresh, Nohad ^b   Chiaroni, Angèle ^a   Guenard, Daniel ^a   Guillou, Catherine ^a  

^a CNRS   (France)

^b Laboratoire de Pharmacochimie   (France)

Author keywords

[No Author keywords available]

Indexed keywords

10 [1 (DIMETHYLAMINO)ETHYL] 1,4A,5,7,7A,9,9A,10,11,12,12A,12B,13,14,14A,14B HEXADECAHYDRO 11 HYDROXY 9A,12A,14B TRIMETHYL 3 (1 METHYLETHYL)OXAZINE 8H INDENO[5',4':4,5]CYCLOHEPTA[1,2 F][3,1]BENZOXAZIN 8 ONE; 10 [1 (DIMETHYLAMINO)ETHYL] 11 HYDROXY 3,9A,12A,14B TETRAMETHYL 1,4A,5,7,7A,9,9A,10,11,12,12A,12B,13,14,14A,14B HEXADECAHYDRO 8H INDENO[5',4':4',5']CYCLOHEPTA[1',2',:3,4]BENZO[1,2 D][1,3]OXAZIN 8 ONE; BUXUS BALEARICA EXTRACT; CHOLINESTERASE; CHOLINESTERASE INHIBITOR; DONEPEZIL; GALANTAMINE; MEMANTINE; N 3 BENZOYLCYCLOXOBUXIDINE F; N 3 ISOBUTYRYLCYCLOXOBUXIDINE F; NATURAL PRODUCT; OXAZINE DERIVATIVE; RIVASTIGMINE; TRITERPENOID; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ARTICLE; CATALYSIS; COMPLEX FORMATION; COMPUTER PROGRAM; CONFORMATION; DRUG BINDING; DRUG ISOLATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME INHIBITION; HIGH THROUGHPUT SCREENING; IC 50; INHIBITION KINETICS; LIGAND BINDING; MOLECULAR DOCKING; MOLECULAR MODEL; NONHUMAN; REACTION OPTIMIZATION; STRUCTURE ACTIVITY RELATION; THREE DIMENSIONAL IMAGING; X RAY ANALYSIS; X RAY CRYSTALLOGRAPHY;

ACETYLCHOLINESTERASE; ANIMALS; BENZOXAZINES; BINDING SITES; BUTYRYLCHOLINESTERASE; CATALYTIC DOMAIN; CATTLE; CHOLINESTERASE INHIBITORS; CRYSTALLOGRAPHY, X-RAY; ELECTROPHORUS; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; SPECIES SPECIFICITY; STRUCTURE-ACTIVITY RELATIONSHIP; TORPEDO; TRITERPENES;

EID: 35848934607     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070536w     Document Type: Article

References (60)

1. Walsh, D. M.; Selkoe, D. J. Deciphering the molecular basis of memory failure in Alzheimer's disease. Neuron 2004, 44, 181-193.
2. Hardy, J.; Selkoe, D. J. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 2002, 297, 353-356.
3. Tolnay, M.; Probst, A. Review: tau protein pathology in Alzheimer disease and related disorders. Neuropathol. Appl. Neurobiol. 1999, 25, 171-187.
4. (a) Bartus, R. T.; Dean, R. L., 3rd; Beer, B.; Lippa, A. S. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982, 217, 408-414.
5. (b) Dunnett, S. B.; Fibiger, H. C. Role of forebrain cholinergic system in learning and memory: relevance to the cognitive deficits of aging and Alzheimer's dementia. Prog. Brain Res. 1993, 98, 413-420.
6. (c) Bartus, R. T. On neurodegenerative diseases, models and treatment strategies: Lessons learned and lessons forgotten a generation following the cholinergic hypothesis. Exp. Neurol. 2000, 163, 495-529.
7. Sugimoto, H. Donepezil hydrochloride: A treatment drug for Alzheimer's disease. Chem. Rec. 2001, 1, 63-73.
8. Jann, M. W. Rivastigmine, a new-generation Cholinesterase inhibitor for the treatment of Alzheimer's disease. Pharmacotherapy 2000, 20, 1-12.
9. (a) Marco-Contelles, J.; Carreiras, M. d. C.; Rodriguez, C.; Villarroya, M.; Garcia, A. G. Synthesis and pharmacology of Galantamine. Chem. Rev. 2006, 106, 116-133.
10. (b) Robinson, D. M.; Plosker, G. L. Galantamine extended release. CNS Drugs 2006, 20, 673-681.
11. Rogawski, M. A.; Wenk, G. L. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev. 2003, 9, 275-308.
12. Soreq, H.; Seidman, S. Acetylcholinesterase: New roles for an old actor. Nat. Rev. Neurosci. 2001, 2, 8-17.
13. Silman, I.; Sussman, J. L. Acetylcholinesterase: Classical and nonclassical functions and pharmacology. Curr. Opin. Pharmacol. 2005, 5, 1-10.
14. Johnson, G.; Moore, S. W. The adhesion function on acetylcholinesterase is located at the peripheral anionic site. Biochem. Biophys. Res. Commun. 1999, 258, 758-762.
15. Giacobini, E. Cholinesterase: New roles in brain function and Alzheimer's disease. Neurochem. Res. 2003, 25, 512-522.
16. Blasina, M. F.; Faria, A. C.; Gardino, P. F.; Hokoc, J. N.; Almeida, O. M.; de Mello, F. G.; Arruti, C.; Dajas, F. Evidence of non-cholinergic function of acetylcholinesterase during development of chicken retina as shown by fasciculin. Cell Tissue Res. 2000, 299, 173-174.
17. Munoz, F. J.; Aldunate, R.; inestrosa, N. C. Peripheral binding site is involved in the neurotrophic activity of acetylcholinesterase. NeuroReport 1999, 26, 3621-3625.
18. Sharma, K. V.; Koenigsberger, C.; Brimijoin, S.; Gigbee, J. W. Direct evidence for an adhesive function in the noncholinergic role of acetylcholinesterase in neurite outgrowth. J. Neurosci. Res. 2001, 63, 165-175.
19. Inestrosa, N. C.; Alarcon, R. Molecular interactions of acetylcholinesterase with senile plaques. J. Physiol. (Paris) 1998, 92, 314-344.
20. (a) Inestrosa, N. C; Alvarez, A.; Calderon, F. Acetylcholienesterase is a senile plaque component that promotes assembly of amyloid β-peptide into Alzheimer's filaments. Mol. Psychiatry 1996, 1, 359-361.
21. (b) De Ferrari, G. V.; Canales, M. A; Shin, I.; Weiner, L. V.; Silman, I.; Inestrosa, N. C. A structural motif that promotes amyloid β-peptide fibril formation. Biochemistry 2001, 40, 10447-10457.
22. De Ferrari, G. V.; Canales, M. A.; Shin, I.; Weiner, L. M.; Silman, I.; Inestrosa, N. C. A structural motif of acetylcholinesterase that promotes amyloid β-peptide fibril formation. Biochemistry 2001, 40, 10447-10457.
23. Bartolini, M.; Bertucci, C.; Cavrini, C.; Andrisano, V. β-Amyloid aggregation induced by human cholinesterase: Inhibition studies. Biochem. Pharmacol. 2003, 65, 407-416.
24. (a) Mary, A.; Renko, D. Z.; Guillou, C.; Thai, C. Potent acetylcholinesterase inhibitors: Design, synthesis and structure-activity relationships of galanthamine bis-ligands. Bioorg. Med. Chem. 1998, 6, 1835-1850.
25. (b) Guillou, C.; Mary, A.; Renko, D. Z.; Gras, E.; Thal, C. Potent acetylcholinesterase inhibitors: Design, synthesis and structure-activity relationships of alkylene linked bis-galanthamine and galanthaminium salts. Bioorg. Med. Chem. Letters 2000, 10, 637-639.
26. (c) Greenblatt, H. M.; Guillou, C.; Guenard, D., Argaman, A.; Botti, S.; Badet, B.; Thal, C.; Silman, I.; Sussman; J. L. The complex of a bivalent derivative of galanthamine with Torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: Implications for structure-based drug design. J. Am. Chem. Soc. 2004, 126, 15405-15411.
27. Vincent, D.; Mathou, T. Inhibiting action of boxwood (Buxus sempervirens and Buxus balearica) on the Cholinesterase of serum. C. R. Hebd. Seances Acad. Sci. 1945, 220, 474-476.
28. Vincent, D.; Sero, I.; Laurent, R. Données pharmacologiques sur le buis. Therapie 1948, 3, 29-32.
29. (a) Choudhary, M. I.; Shahnaz, S.; Parveen, S.; Khalid, A.; Ayatollahi, S. A. M.; Atta-ur-Rahman; Parvez, M. New triterpenoid alkaloid cholinesterase inhibitors from Buxus hyrcana. J. Nat. Prod. 2003, 66, 739-742.
30. (b) Atta-ur-Rahman; Parveen, S.; Khalid, A.; Farooq, A.; Ayatollahi, S. A. M.; Choudhary, M. I. Acetylcholinesterase inhibiting triterpenoidal alkaloids from Buxus hyrcana. Heterocycles 1998, 49, 481-488.
31. Atta-ur-Rahman Parveen, S.; Khalid, A.; Farooq, A.; Choudhary, M. I. Acetyl and butyrylcholinesterase-inhibiting triterpenoids from Buxus papillosa. Phytochemistry 2001, 58, 963-968.
32. Atta-ur-Rahman; Zaheer ul, H.; Feroz, F.; Khalid, A.; Nawaz, S. A.; Khan, M. R.; Choudhary, M. I. Cholinesterase-inhibiting new steroidal alkaloids from Sarcococca hookeriana of Nepalese origin. Helv. Chim. Acta 2004, 87, 439-448.
33. Atta-ur-Rahman; Feroz, F.; Zaheer ul, H.; Nawaz, S. A.; Khan, M. R.; Choudhary, M. I. New steroidal alkaloids from sarcococca. Nat. Prod. Res. 2003, 17, 235-241.
34. Kalauni, S. K.; Choudhary, M. I.; Khalid, A.; Manandhar, M. D.; Shaheen, F.; Atta-ur-Rahman; Gewali, M. B. New Cholinesterase inhibiting steroidal alkaloids from the leaves of Sarcococca coriacea of Nepalese origin. Chem. Pharm. Bull. 2002, 50, 1423-1426.
35. Herlem, D. These: Alkaloids from Buxus balearica Willd (Buxacées) - Isolation and structural determination; Science Faculty of Paris: Paris, 1967.
36. Compound 1 has been previously prepared by pyrolysis at 210°C under 0.01 mmHg in the presence of tetramethylammonium hydroxide. Herlem-Gaulier, D.; Kuong-Huu-Lainé, F.; Goutarel, R.; Magdeleine, M. J. Alcaloïdes stéroïdiques LXXII. Alcaloïdes du groupe des cylcloxobuxidines retirés du Buxus balearica Willd: N-3-iso-Butyryl cycloxobuxidine-F (baléabuxidine), N-3-isobutyryl cycloxobuxidine-H, N-3-benzoyl cycloxobuxidine-F et cycloxobuxoxazine-C. Bull. Soc. Chim. Fr. 1968, 2, 763-773.
37. Shaw, J. T.; Corbett, W. L.; Layman, D. L.; Cuny, G. D.; Kerschner, J. Fused s-triazino heterocycles. XV. 13H-4,6,7,13a,13c- pentaazabenzo[hi]chrysene, 13H,4,7,13a,13c- tetraazabenzo [hi]chrysene and 7H-3,7,10,10b-tetraazacyclohepta[de] naphtalene, three new ring systems J. Heterocycl. Chem. 1988, 25, 1837-1840.
38. Mary, A.; Zafiarisoa, D.; Guillou, C.; Thal, C. Selective N-demethylation of galanthamine via a nonclassical Polonovski reaction. Tetrahedron Lett. 1997, 38, 5151-5152.
39. Ellman, G. L.; Courtney, K. D.; Andres, V.; Featherstone, R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7, 88-95.
40. Giacobini, E. Butyrylcholinesterase its functions and inhibitors; Martin Dunitz: 2003.
41. Kuhl D. E.; Koeppe R. A.; Snyder, S. E.; Minoshima, S., Frey, K. A.; Kilbourn, M. R. Ann. Neurol. 2006, 59, 13-20.
42. Khalid, A.; Zaheer-ul-Haq Anjum, S.; Riaz Khan, M.; Atta-ur-Rahman, Choudhary, M. I. Kinetic and structure-activity relationship studies on pregnane-type steroidal alkaloids that inhibit cholinesterases. Bioorg. Med. Chem. 2004, 12, 1995-2003.
43. Robaire, B.; Kato, G. Effect of edrophonium, eserine, decamethonium, D-tubocurarine, and gallamine on the kinetics of membrane-bound and solubilized Eel acetylcholinesterase. Mol. Pharmacol. 1975, 11, 722-734.
44. Harel, M.; Schalk, I.; Ehret-Sabattier, L.; Bouet, F.; Goeldner, M.; Hirth, C.; Axelsen, P.; Silman, I.; Sussman, J. L. Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Proc. Nat. Acad. Sci. U.S.A. 1993, 90, 9031-9035.
45. Khalid, A.; Azim, M. K.; Parveen, S.; Atta-ur-Rahman, Choudhary, M. I. Structural basis of acetylcholinesterase inhibition by triterpenoidal alkaloids. Biochem. Biophys. Res. Comm. 2005, 331, 1528-32.
46. For a recent application, see: Roux, C.; Gresh, N.; Perera, L. E.; Piquemal, J.-P.; Salmon, L. Binding of 5-phospho-D-arabinonohydroxamate and 5-phospho-D-arabinonate inhibitors to zinc phosphomannose isomerase from Candida albicans studied by polarizable molecular mechanics and quantum mechanics. J. Comput. Chem. 2007, 28, 938-957.
47. Wu, H. J.; Roux, B. Calculation of absolute protein-ligand binding free energy from computer simulation. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 6825-6830.
48. (a) Chipot, C.; Pearlman, D. A. Free energy calculations. The long and winding gilded road. Mol. Simul. 2002, 28, 1-12.
49. (b) Chipot, C.; Rozanska, X.; Dixit, S. B. Can free energy calculations be fast and accurate at the same time? Binding of low-affinity, nonpeptide inhibitors to the SH2 domain of the src protein. J. Comp.-Aided Mol. Des. 2005, 19, 765-770.
50. Raves, M. L.; Harel, M.; Pang, Y. P.; Silman, I.; Kozikowski, A. P.; Sussman, J. L. 3D structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A. Nat. Struct. Biol. 1997, 4, 57-63.
51. Sussman, J. L.; Harel, M.; Frolow, F.; Varon, L.; Toker, L.; Futerman, A. H.; Silman, I., Purification and crystallization of a dimeric form of acetylcholinesterase from Torpedo californica subsequent to solubilization with phosphatidylinositol-specific phospholipase C. J. Mol. Biol. 1988, 203, 821-823.
52. Accelrys Inc., 9685 Scranton Rd., San Diego, CA 92121-3752.
53. Plocki, S.; Tavarès-Camarinha, F.; Ahamada-Himidi, A.; Aoun, D.; Dong, C. Z.; Massicot, F.; Huet, J.; Adolphe-Pierre, S.; Chau, F.; Ombetta, J. E.; Gresh, N.; Godfroid, J. J.; Heymans, F. Inhibition of secretory phospholipase A2. Molecular modeling, design, and synthesis of less lipophilic derivatives of 4,5-dihydro-3-(4-tetradecyl-oxybenzyl)-1,2,4H oxadiazol-5-one specific for group 11 enzyme. Eur. J. Org. Chem. 2005, 2747-2757.
54. Honig, B.; Sharp, K.; Yang, A. S. Macroscopic models of aqueous solutions: Biological and chemical applications. J. Phys. Chem. 1993, 97, 1101-1109.
55. CCDC 651096 contains the Supplementary Crystallographic data for compound 1. These data can be obtained free of charge via www.ccdc.cam.ac.uk or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K. (fax: +44-(0)1223-336033, E-mail: deposit@ccdc.cam.ac.uk).
56. Otwinowski, Z.; Minor, W. Processing of X-ray Diffraction Data Collected in Oscillation Model, Methods in Enzymology, Volume 276: Macromolecular Crystallography, part A; Carter, C. W., Jr., Sweet, R. M., Eds.; Academic Press: New York, 1997; pp 307-326.
57. Sheldrick, G. M. SHELXS86. Acta Cryst. A 1990, 46, 467-473.
58. Sheldrick, G. M. SHELX97, Program for the Refinement of Crystal Structures; Univ. of Göttingen: Germany, 1997.
59. (a) Spek, A. L.; Platon, A multipurpose crystallographic tool; Utrecht University: Utrecht, The Netherlands,
60. (b) Spek, A. L. Single-crystal structure validation with the program Platon. J. Appl. Cryst. 2003, 36, 7-13.