Indole alkaloids and semisynthetic indole derivatives as multifunctional scaffolds aiming the inhibition of enzymes related to neurodegenerative diseases - a focus on Psychotria L. genus

Current Topics in Medicinal Chemistry

Volumn 14, Issue 8, 2014, Pages 1056-1075

  Klein Júnior, Luiz Carlos ^a   Passos, Carolina dos Santos ^a,b   Moraes, Aline Pereira ^c   Wakui, Vinicius Galvão ^c   Konrath, Eduardo Luis ^a   Nurisso, Alessandra ^b   Carrupt, Pierre Alain ^b   de Oliveira, Cecilia Maria Alves ^c   Kato, Lucilia ^c   Henriques, Amélia Teresinha ^a  

^a FEDERAL UNIVERSITY OF RIO GRANDE DO SUL   (Brazil)

^b UNIVERSITY OF GENEVA   (Switzerland)

^c FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

Author keywords

Cholinesterases inhibition; Indole alkaloids; Indole derivatives; Molecular docking; Monoamine oxidases inhibition; Multi target scaffolds; Neurodegenerative diseases; Psychotria

Indexed keywords

5 (1H INDOL 3 YLMETHYL) 2 THIOXOIMIDAZOLIDIN 4 ONE; 5 (1H INDOL 3 YLMETHYL) 2 THIOXOIMIDAZOLIN 4 ONE; 5 (1H INDOL 3 YLMETHYL) 3 METHYL 2 THIOXOIMIDAZOLIDIN 4 ONE; 5 (1H INDOL 3 YLMETHYL)IMIDAZOLIDINE 2,4 DIONE; 5 (1HINDOL 3 YLMETHYL) 3 METHYL 2 THIOXOIMIDAZOLIDIN 4 ONE; ACETYLCHOLINESTERASE; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME A; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME B; BAHIENOSIDE A; BUFOTENINE; CHOLINESTERASE; DESOXYCORDIOFOLINE; INDOLE ALKALOID; INDOLE DERIVATIVE; METHYL 2 (AMINO N (2 (4 METHYLCYCLOHEX 3 ENYL)PROPAN 2 YL)METHANETHIOAMINO) 3 (1H INDOL 3 YL)PROPANOATE; METHYL 2 (AMINO N (2 (4 METHYLCYCLOHEX 3 ENYL)PROPAN 2 YL)METHANETHIOAMINO) 3 (1H INDOL 3 YL)PROPANOATE); UNCLASSIFIED DRUG; AMINE OXIDASE (FLAVIN CONTAINING); CENTRAL NERVOUS SYSTEM AGENTS; CHOLINESTERASE INHIBITOR; MONOAMINE OXIDASE INHIBITOR;

ADULT; ANIMAL EXPERIMENT; ARTICLE; COLORIMETRY; DEGENERATIVE DISEASE; DRUG ISOLATION; ENZYMATIC ASSAY; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN EXPERIMENT; IC 50; LIQUID CHROMATOGRAPHY; MALE; MOLECULAR DOCKING; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PSYCHOTRIA; RAT; CHEMICAL STRUCTURE; CHEMISTRY; METABOLISM; NEURODEGENERATIVE DISEASES;

CENTRAL NERVOUS SYSTEM AGENTS; CHOLINESTERASE INHIBITORS; CHOLINESTERASES; HUMANS; INDOLE ALKALOIDS; INDOLES; MOLECULAR STRUCTURE; MONOAMINE OXIDASE; MONOAMINE OXIDASE INHIBITORS; NEURODEGENERATIVE DISEASES; PSYCHOTRIA;

EID: 84903740289     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/1568026614666140324142409     Document Type: Article

References (114)

1. Ballard, C.; Gauthier, S.; Corbett, A.; Brayne, C.; Aarsland, D.; Jones, E. Alzheimer's disease. Lancet, 2011, 377(9770), 1019-1031.
2. Rizzo, S.; Bisi, A.; Bartolini, M.; Mancini, F.; Belluti, F.; Gobbi, S.; Andrisano, V.; Rampa, A. Multi-target strategy to address Alzheimer's disease: design, synthesis and biological evaluation of new tacrine-based dimers. Eur. J. Med. Chem., 2011, 46(9), 4336-4343.
3. Goedert, M.; Spillantini, M.G. A century of Alzheimer's disease. Science, 2006, 314(5800), 777-781.
4. Craig, L.A.; Hong, N.S.; McDonald, R.J. Revisiting the cholinergic hypothesis in the development of Alzheimer's disease. Neurosci. Biobehav. Rev., 2011, 35(6), 1397-1409.
5. Shen, Z.X. Brain cholinesterases: II. The molecular and cellular basis of Alzheimer's disease. Med. Hypotheses, 2004, 63(2), 308-321.
6. Terry, A.V., Jr.; Buccafusco, J.J. The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J. Pharmacol. Exp. Ther., 2003, 306(3), 821-827.
7. 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(2), 495-529.
8. Zahodne, L.B.; Fernandez, H.H. Pathophysiology and treatment of psychosis in Parkinson's disease: a review. Drugs Aging, 2008, 25(8), 665-682.
9. Williams-Gray, C.H.; Foltynie, T.; Lewis, S.J.; Barker, R.A. Cognitive deficits and psychosis in Parkinson's disease: a review of pathophysiology and therapeutic options. CNS Drugs, 2006, 20(6), 477-505.
10. Cavalli, A.; Bolognesi, M.L.; Minarini, A.; Rosini, M.; Tumiatti, V.; Recanatini, M.; Melchiorre, C. Multi-target-directed ligands to combat neurodegenerative diseases. J. Med. Chem., 2008, 51(3), 347-372.
11. Bolognesi, M.L.; Simoni, E.; Rosini, M.; Minarini, A.; Tumiatti, V.; Melchiorre, C. Multitarget-directed ligands: innovative chemical probes and therapeutic tools against Alzheimer's disease. Curr. Top Med.Chem., 2011, 11(22), 2797-2806.
12. Geldenhuys, W.J.; Youdim, M.B.; Carroll, R.T.; Van der Schyf, C.J. The emergence of designed multiple ligands for neurodegenerative disorders. Prog. Neurobiol, 2011, 94(4), 347-359.
13. Novaroli, L.; Daina, A.; Bertolini, F.; Di Giovanni, S.; Bravo, J.; Reist, M.; Carrupt, P.-A. Identification of Novel Multifunctional Compounds for the Treatment of Some Aging Related Neurodegenerative Diseases. Chimia, 2005, 59(6), 315-320.
14. Youdim, M.B.H.; Buccafusco, J.J. Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders. Trends Pharmacol. Sci., 2005, 26(1), 27-35.
15. Konrath, E.L.; Passos, C.S.; Klein-Júnior, L.C.; Henriques, A.T. Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer's disease. J. Pharm. Pharmacol, 2013., 65(12), 1701-1725.
16. Brierley, D.I.; Davidson, C. Developments in harmine pharmacology--implications for ayahuasca use and drug-dependence treatment. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2012, 39(2), 263-272.
17. Wang, Y.H.; Samoylenko, V.; Tekwani, B.L.; Khan, I.A.; Miller, L.S.; Chaurasiya, N.D.; Rahman, M.M.; Tripathi, L.M.; Khan, S.I.; Joshi, V.C.; Wigger, F.T.; Muhammad, I. Composition, standardization and chemical profiling of Banisteriopsis caapi, a plant for the treatment of neurodegenerative disorders relevant to Parkinson's disease. J. Ethnopharmacol, 2010, 128(3), 662-671.
18. Herraiz, T. Analysis of the bioactive alkaloids tetrahydro-beta-carboline and beta-carboline in food. J. Chromatogr. A, 2000, 881(1-2), 483-499.
19. Cao, R.; Peng, W.; Wang, Z.; Xu, A. Beta-Carboline alkaloids: biochemical and pharmacological functions. Curr. Med. Chem., 2007, 14(4), 479-500.
20. Samoylenko, V.; Rahman, M.M.; Tekwani, B.L.; Tripathi, L.M.; Wang, Y.H.; Khan, S.I.; Khan, I.A.; Miller, L.S.; Joshi, V.C.; Muhammad, I. Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson's disease. J. Ethnopharmacol, 2010, 127(2), 357-367.
21. Herraiz, T.; Chaparro, C. Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids act as potent and reversible inhibitors. Biochem. Biophys. Res. Commun., 2005, 326(2), 378-386.
22. Herraiz, T.; Chaparro, C. Human monoamine oxidase enzyme inhibition by coffee and p-carbolines norharman and harman isolated from coffee. Life Sciences, 2006, 78(8), 795-802.
23. Saidemberg, D.M.; Ferreira, M.A.B.; Takahashi, T.N.; Gomes, P.C.; Cesar-Tognoli, L.M.M.; da Silva-Filho, L.C.; Tormena, C.F.; da Silva, G.V.J.; Palma, M.S. Monoamine oxidase inhibitory activities of indolylalkaloid toxins from the venom of the colonial spider Parawixia bistriata: Functional characterization of PwTX-I. Toxicon, 2009, 54(6), 717-724.
24. Son, S.-Y.; Ma, J.; Kondou, Y.; Yoshimura, M.; Yamashita, E.; Tsukihara, T. Structure of human monoamine oxidase A at 2.2-Å resolution: The control of opening the entry for substrates/inhibitors. Proc. Natl. Acad. Sci. U S A, 2008, 105(15), 5739-5744.
25. Reniers, J.; Robert, S.; Frederick, R.; Masereel, B.; Vincent, S.; Wouters, J. Synthesis and evaluation of p-carboline derivatives as potential monoamine oxidase inhibitors. Bioorg. Med. Chem., 2011, 19(1), 134-144.
26. Passos, C.S.; Simões-Pires, C.A.; Nurisso, A.; Soldi, T.C.; Kato, L.; De Oliveira, C.M.A.; De Faria, E.O.; Marcourt, L.; Gottfried, C; Carrupt, P.A.; Henriques, A.T. Indole alkaloids of Psychotria as multifunctional cholinesterases and monoamine oxidases inhibitors. Phytochemistry, 2013, 86, 8-20.
27. Yu, A.M.; Idle, J.R.; Krausz, K.W.; Kupfer, A.; Gonzalez, F.J. Contribution of individual cytochrome P450 isozymes to the O-demethylation of the psychotropic beta-carboline alkaloids harma-line and harmine. J. Pharmacol. Exp. Ther., 2003, 305(1), 315-322.
28. Riba, J.; Valle, M.; Urbano, G.; Yritia, M.; Morte, A.; Barbanoj, M.J. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics. J. Pharmacol. Exp. Ther., 2003, 306(1), 73-83.
29. Riba, J.; McIlhenny, E.H.; Valle, M.; Bouso, J.C.; Barker, S.A. Metabolism and disposition of N,N-dimethyltryptamine and har-mala alkaloids after oral administration of ayahuasca. Drug Test. Anal, 2012, 4(7-8), 610-616.
30. Freeman, S.; Alder, J.F. Arylethylamine psychotropic recreational drugs: A chemical perspective. Eur. J. Med. Chem., 2002, 37(7), 527-539.
31. Moron, J.A.; Campillo, M.; Perez, V.; Unzeta, M.; Pardo, L. Molecular determinants of MAO selectivity in a series of indolylmeth-ylamine derivatives: biological activities, 3D-QSAR/CoMFA analysis, and computational simulation of ligand recognition. J. Med. Chem., 2000, 43(9), 1684-1691.
32. Lewellyn, K.; Bialonska, D.; Chaurasiya, N.D.; Tekwani, B.L.; Zjawiony, J.K. Synthesis and evaluation of aplysinopsin analogs as inhibitors of human monoamine oxidase A and B. Bioorg. Med. Chem. Lett., 2012, 22(15), 4926-4929.
33. Orhan, G.; Orhan, I.; Öztekin-Subutay, N.; Ak, F.; Şener, B. Contemporary anticholinesterase pharmaceuticals of natural origin and their synthetic analogues for the treatment of Alzheimer's disease. Recent Pat. CNS Drug Discov.,2009, 4(1), 43-51.
34. Takahashi, J.; Hijikuro, I.; Kihara, T.; Murugesh, M.G.; Fuse, S.; Tsumura, Y.; Akaike, A.; Niidome, T.; Takahashi, T.; Sugimoto, H. Design, synthesis and evaluation of carbamate-modified (-)-N1-phenethylnorphysostigmine derivatives as selective butyrylcholinesterase inhibitors. Bioorg. Med. Chem. Lett.,2010, 20(5), 1721-1723.
35. Ul-Haq, Z.; Mahmood, U.; Jehangir, B. Ligand-based 3D-QSAR studies of physostigmine analogues as acetylcholinesterase inhibitors. Chem. Biol. Drug Des., 2009, 74(6), 571-581.
36. Zhan, Z.J.; Bian, H.L.; Wang, J.W.; Shan, W.G. Synthesis of physostigmine analogues and evaluation of their anticholinesterase activities. Bioorg. Med. Chem. Lett., 2010, 20(5), 1532-1534.
37. Yu, Q.; Holloway, H.W.; Flippen-Anderson, J.L.; Hoffman, B.; Brossi, A.; Greig, N.H. Methyl analogues of the experimental Alzheimer drug phenserine: Synthesis and structure/activity relationships for acetyl- and butyrylcholinesterase inhibitory action. J. Med. Chem., 2001, 44(24), 4062-4071.
38. Shinada, M.; Narumi, F.; Osada, Y.; Matsumoto, K.; Yoshida, T.; Higuchi, K.; Kawasaki, T.; Tanaka, H.; Satoh, M. Synthesis of phenserine analogues and evaluation of their cholinesterase inhibitory activities. Bioorg. Med. Chem., 2012, 20(16), 4901-4914.
39. Yu, Q.S.; Holloway, H.W.; Utsuki, T.; Brossi, A.; Greig, N.H. Synthesis of novel phenserine-based-selective inhibitors of butyrylcholinesterase for Alzheimer's disease. J. Med. Chem.,1999, 42(10), 1855-1861.
40. Takahashi, J.; Hijikuro, I.; Kihara, T.; Murugesh, M.G.; Fuse, S.; Kunimoto, R.; Tsumura, Y.; Akaike, A.; Niidome, T.; Okuno, Y.; Takahashi, T.; Sugimoto, H. Design, synthesis, evaluation and QSAR analysis of N1-substituted norcymserine derivatives as selective butyrylcholinesterase inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(5), 1718-1720.
41. Yu, Q.S.; Zhu, X.; Holloway, H.W.; Whittaker, N.F.; Brossi, A.; Greig, N.H. Anticholinesterase activity of compounds related to geneserine tautomers. N-oxides and 1,2-oxazines. J. Med. Chem., 2002, 45(17), 3684-3691.
42. Becher, P.G.; Beuchat, J.; Gademann, K.; Juttner, F. Nostocar-boline: isolation and synthesis of a new cholinesterase inhibitor from Nostoc 78-12A. J. Nat. Prod., 2005, 68(12), 1793-1795.
43. Becher, P.G.; Baumann, H.I.; Gademann, K.; Jüttner, F. The cya-nobacterial alkaloid nostocarboline: an inhibitor of acetylcholinesterase and trypsin. J. App. Phycol, 2009, 21(1), 103-110.
44. Schott, Y.; Decker, M.; Rommelspacher, H.; Lehmann, J. 6-Hydroxy- and 6-methoxy-p-carbolines as acetyl- and butyrylcho-linesterase inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(22), 5840-5843.
45. Geissler, T.; Brandt, W.; Porzel, A.; Schlenzig, D.; Kehlen, A.; Wessjohann, L.; Arnold, N. Acetylcholinesterase inhibitors from the toadstool Cortinarius infractus. Bioorg. Med. Chem., 2010, 18(6), 2173-2177.
46. Torres, J.M.; Lira, A.F.; Silva, D.R.; Guzzo, L.M.; Sant'Anna, CM.; Kummerle, A.E.; Rumjanek, V.M. Structural insights into cholinesterases inhibition by harmane beta-carbolinium derivatives: a kinetics-molecular modeling approach. Phytochemistry, 2012, 81, 24-30.
47. Cardoso, C.L.; Castro-Gamboa, I.; Siqueira Silva, D.H.; Furlan, M.; Epifanio, R.D.A.; Da Cunha Pinto, Â.; De Rezende, CM.; Lima, J.A.; Da Silva Bolzani, V. Indole glucoalkaloids from Chi-marrhis turbinata and their evaluation as antioxidant agents and acetylcholinesterase inhibitors. J. Nat. Prod., 2004, 67(11), 1882-1885.
48. Pereira, D.M.; Ferreres, F.; Oliveira, J.M.A.; Gaspar, L.; Faria, J.; Valentão, P.; Sottomayor, M.; Andrade, P.B. Pharmacological effects of Catharanthus roseus root alkaloids in acetylcholinesterase inhibition and cholinergic neurotransmission. Phytomedicine, 2010, 17(8-9), 646-652.
49. Bremer, B.; Eriksson, T. Time three of Rubiaceae: phylogeny and dating the family, subfamilies, and tribes. Int. J. Plant Sci., 2009, 170, 766-793.
50. Davis, A.P.; Bridson, D.; Jarvis, C; Govaerts, R. The typification and characterization of the genus Psychotria L. (Rubiaceae). Bot. J. Linn. Soc, 2001, 135(1), 35-42.
51. Moraes, T.M.S.; Rabelo, G.R.; Alexandrino, C.R.; Silva Neto, S.J.; Da Cunha, M. Comparative leaf anatomy and micromorphology of Psychotria species (Rubiaceae) from the Atlantic Rainforest. Acta Bot. Bras., 2011, 25(1), 178-190.
52. Steyermark, J.A. In The Botany of Guayana Highland - Part IX. Maguire, B.M.a.C, Ed., 1972; Vol. 23, pp 404-717.
53. Andersson, L. Relationships and generic circumscriptions in the Psychotria complex (Rubiaceae, Psychotrieae). Syst. Geogr. Pl., 2002, 72, 167-202.
54. Brand, G.; Henriques, A.T.; Passos, C.S.; Baldoqui, D.C; Santin, S.M.O.; Costa, W.F.; Sarragiotto, M.H. Pyrrolidinoindoline alkaloids from Margaritopsis cymuligera (Muell. Arg.) CM. Taylor (Rubiaceae). Biochem. Syst. Ecol, 2012, 45, 155-157.
55. Andersson, L. Margaritopsis (Rubiaceae, Psychotrieae) is a pan-tropical genus. Syst. Geogr. Pl., 2001, 71, 73-85.
56. Lopes, S.O.; Von Poser, G.L.; Kerber, V.A.; Farias, F.M.; Konrath, E.L.; Moreno, P.; Sobral, M.E.; Zuanazzi, J.A.; Henriques, A.T. Taxonomic significance of alkaloids and iridoid glucosides in the tribe Psychotrieae (Rubiaceae). Biochem. Syst. Ecol, 2004, 32(12), 1187-1195.
57. Kerber, V.A.; Gregianini, T.S.; Paranhos, J.T.; Schwambach, J.; Farias, F.; Fett, J.P.; Fett-Neto, A.G.; Zuanazzi, J.A.; Quirion, J.C; Elizabetsky, E.; Henriques, A.T. Brachycerine, a novel monoter-pene indole alkaloid from Psychotria brachyceras. J. Nat. Prod., 2001, 64(5), 677-679.
58. Kerber, V.A.; Passos, C.S.; Verli, H.; Fett-Neto, A.G.; Quirion, J.P.; Henriques, A.T. Psychollatine, a glucosidic monoterpene indole alkaloid from Psychotria umbellata. J. Nat. Prod., 2008, 71(4), 697-700.
59. Dusman, L.T.; Marinho Jorge, T.C; de Souza, M.C; Eberlin, M.N.; Meurer, E.C; Bocca, C.C.; Basso, E.A.; Sarragiotto, M.H. Monoterpene indole alkaloids from Palicourea crocea. J. Nat. Prod., 2004, 67(11), 1886-1888.
60. Narine, L.L.; Maxwell, A.R. Monoterpenoid indole alkaloids from Palicourea crocea. Phytochem. Lett., 2009, 2(1), 34-36.
61. Zeches, M.; Richard, B.; Gueye-M'Bahia, L.; Le Men-Olivier, L.; Delaude, C. Constituants des Ecorces de Racine de Nauclea pobe-guinii. J. Nat. Prod., 1985, 48, 42-46.
62. Erdelmeier, C.A.; Wright, A.D.; Orjala, J.; Baumgartner, B.; Rali, T.; Sticher, O. New indole alkaloid glycosides from Nauclea orien-talis. Planta Med., 1991, 57(2), 149-152.
63. Shigemori, H.; Kagata, T.; Ishiyama, H.; Morah, F.; Ohsaki, A.; Kobayashi, J. Naucleamides A-E, new monoterpene indole alkaloids from Nauclea latifolia. Chem. Pharm. Bull. (Tokyo), 2003, 51(1), 58-61.
64. Kakugushi, Y.; Ishiyama, H.; Kubota, T.; Kobayashi, J. Nau-clemide F, a new monoterpene indole alkaloid from Nauclea latifolia. Heterocycles, 2009, 79, 765-771.
65. Xuan, W.D.; Chen, H.S.; Yuan, Z.X.; Zhu, P. Alkaloidal constituents from Nauclea officinalis. Chin. J. Nat. Med., 2004, 3, 181-183.
66. Farias, F.M.; Konrath, E.L.; Zuanazzi, J.A.S.; Henriques, A.T. Strictosamide from Psychotria nuda (Cham. et Schltdl) Wawra (Rubiaceae). Biochem. Syst. Ecol, 2008, 36, 919-920.
67. Do Nascimento, C.A.; Liao, L.M.; Kato, L.; Da Silva, C.C.; Tanaka, CM.; Schuquel, I.T.; De Oliveira, CM. A tetrahydro beta-carboline trisaccharide from Palicourea coriacea (Cham.) K. Schum. Carbo-hydr. Res., 2008, 343(6), 1104-1107.
68. Do Nascimento, C.A.; Gomes, M.S.; Liao, L.M.; De Oliveira, CM.; Kato, L.; Da Silva, C.C.; Tanaka, C.M.A. Alkaloids from Palicourea coriaceae (Cham.) K. Schum. Z. Naturforsch B, 2006, 61, 1443-1446.
69. Stuart, K.L.; Woo-Ming, R.B. Palicourea alkaloids. Structure of Palinine. Tetrahedron Lett., 1974, 44, 3853-3856.
70. Vencato, I.; Silva, F.M.D.; Oliveira, C.M.A.D.; Kato, L.; Tanaka, C.M.A.; Silva, C.C.D.; Sabino, J.R. Vallesiachotamine. Acta Crystallogr. Sect. E, 2006, 62(2), o429-o431.
71. Valverde, J.; Tamayo, G.; Manfred, H. P-Carboline monoterpenoid glucosides from Palicourea adusta. Phytochemistry, 1999, 52(8), 1485-1489.
72. Berger, A.; Fasshuber, H.; Schinnerl, J.; Brecker, L.; Greger, H. Various types of tryptamine-iridoid alkaloids from Palicourea acuminata (=Psychotria acuminata, Rubiaceae). Phytochem. Lett., 2012, 5(3), 558-562.
73. Adjibadé, Y. Pharmacognosie du Psychotria forsteriana A. Gray (Rubiaceae). Aspects botanique, chimique et essais pharma-cologiques preliminares. Université Louis Pasteur de Strasbourg I, Paris, 1989.
74. Leal, M.B. Estudo Psicofarmacológico de Espécies de Psychotria (RUBIACEAE) do Estado do Rio Grande do Sul. Universidade Federal do Rio Grande do Sul, Porto Alegre, 1994.
75. Dos Santos Passos, C; Soldi, T.C; Torres Abib, R.; Anders Apel, M.; Simões-Pires, C; Marcourt, L.; Gottfried, C; Henriques, A.T. Monoamine oxidase inhibition by monoterpene indole alkaloids and fractions obtained from Psychotria suterella and Psychotria lac-iniata. J. Enzyme Inhib. Med. Chem., 2013, 28(3), 611-618.
76. Simoes-Pires, C.A.; Farias, F.N.; Marston, A.; Queiroz, E.F.; Chaves, C.G.; Henriques, A.T.; Hostettmann, K. Indole monoter-penes with antichemotactic activity from Psychotria myriantha: Chemotaxonomic significance. Nat. Prod. Comm., 2006, 1, 1101-1106.
77. Farias, F.M. Psychotria myriantha Müll Arg. (Rubiaceae): carac-terização dos alcaloides e avaliação das atividades antiquimi-otáxica e sobre o sistema nervoso central. Universidade Federal do Rio Grande do Sul, Porto Alegre, 2006.
78. Farias, F.M.; Passos, C.S.; Arbo, M.D.; Zuanazzi, J.A.; Steffen, V.M.; Henriques, A.T. Monoamine levels in rat striatum after acute intraperitoneal injection of strictosidinic acid isolated from Psychotria myriantha Mull. Arg. (Rubiaceae). Phytomedicine, 2010, 17(3-4), 289-291.
79. Farias, F.M.; Passos, C.S.; Arbo, M.D.; Barros, D.M.; Gottfried, C; Steffen, V.M.; Henriques, A.T. Strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae), decreases serotonin levels in rat hippocampus. Fitoterapia, 2012, 83(6), 1138-1143.
80. Both, F.L.; Kerber, V.A.; Henriques, A.T.; Elisabetsky, E. Analgesic Properties of Umbellatine from Psychotria umbellata. Pharm. Biol, 2002, 40, 336-341.
81. Both, F.L.; Meneghini, L.; Kerber, V.A.; Henriques, A.T.; Elisabetsky, E. Psychopharmacological profile of the alkaloid psychollatine as a 5HT2A/C serotonin modulator. J. Nat. Prod., 2005, 68(3), 374-380.
82. Both, F.L.; Meneghini, L.; Kerber, V.A.; Henriques, A.T.; Elisa-betsky, E. Role of glutamate and dopamine receptors in the psy-chopharmacological profile of the indole alkaloid psychollatine. J. Nat. Prod., 2006, 69(3), 342-345.
83. Konrath, E.L. Investigação in vitro do Efeito Neurotóxico, Antioxi-dante e Anticolinesterásico de Alcalóides e Avaliação de Parâmet-ros de Estresse Oxidativo em Fatias de Hipocampo Submetidas à Privação de Oxigênio e Glicose. Universidade Federal do Rio Grande do Sul, Porto Alegre, 2006.
84. Passos, C.S. Psicolatina: caracterização conformacional e avaliação do efeito sobre os níveis de aminoácidos excitatórios e inibitórios em regiões cerebrais de roedores. Universidade Federal do Rio Grande do Sul, Porto Alegre, 2008.
85. Paul, J.H.; Maxwell, A.R.; Reynolds, W.F. Novel bis(mono-terpenoid) indole alkaloids from Psychotria bahiensis. J. Nat. Prod., 2003, 66(6), 752-754.
86. Brown, R.T.; Warambwa, B.F.M. Adina alkaloids: Isolation of desoxycordifoline. Phytochemistry, 1978, 17(9), 1686-1687.
87. Brandt, V.; Tits, M.; Geerlings, A.; Frédérich, M.; Penelle, J.; De-laude, C; Verpoorte, R.; Angenot, L. P-Carboline glucoalkaloids from Strychnos mellodora. Phytochemistry, 1999, 51(8), 1171-1176.
88. Wang, Y.; Chen, C. Synthesis of a deuterium labelled standard of bufotenine (5-HO-DMT). J. Labelled Com. Rad., 2007, 50(14), 1262-1265.
89. Patching, S.G. Efficient syntheses of 13C and 14C labelled 5 benzyl and 5 indolylmethyl L hydantoins. J. Labelled Comp. Radiopharm., 2011, 54(2), 110-114.
90. Johnson, T.B.; Nicolet, B.H. Hydantoins: the synthesis of 2-thiohydantoin. J. Am. Chem. Soc, 1911, 22(12), 1973-1978.
91. Teng, X.; Degterev, A.; Jagtap, P.; Xing, X.; Choi, S.; Denu, R.; Yuan, J.; Cuny, G.D. Structure-activity relationship study of novel necroptosis inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(22), 5039-5044.
92. Tang, J.G.; Wang, Y.H.; Wang, R.R.; Dong, Z.J.; Yang, L.M.; Zheng, Y.T.; Liu, J.K. Synthesis of analogues of flazin, in particular, flazinamide, as promising anti-HIV agents. Chem. Biodivers., 2008, 5(3), 447-460.
93. da Silva, A.P.; Martini, M.V.; de Oliveira, CM.; Cunha, S.; de Carvalho, J.E.; Ruiz, A.L.; da Silva, C.C. Antitumor activity of (-)-alpha-bisabolol-based thiosemicarbazones against human tumor cell lines. Eur. J. Med. Chem., 2010, 45(7), 2987-2993.
94. Ellman, G.L.; Courtney, K.D.; Andres, V., Jr.; Feather-Stone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol, 1961, 7, 88-95.
95. Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193(1), 265-275.
96. Son, S.Y.; Ma, J.; Kondou, Y.; Yoshimura, M.; Yamashita, E.; Tsukihara, T. Structure of human monoamine oxidase A at 2.2-A resolution: the control of opening the entry for substrates/inhibitors. Proc. Natl. Acad. Sci. U S A, 2008, 105(15), 5739-5744.
97. Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The Protein Data Bank. Nucleic Acids Res., 2000, 28(1), 235-242.
98. Clark, M.; Cramer R.D.; Van Opdenbosch, N. Validation of the general purpose tripos 5.2 force field. J. Comp. Chem., 1989, 10(8), 982-1012.
99. Verdonk, M.L.; Cole, J.C.; Hartshorn, M.J.; Murray, C.W.; Taylor, R.D. Improved protein-ligand docking using GOLD. Proteins, 2003, 52(4), 609-623.
100. Nurisso, A.; Bravo, J.; Carrupt, P.A.; Daina, A. Molecular docking using the molecular lipophilicity potential as hydrophobic descriptor: impact on GOLD docking performance. J. Chem. Inf. Model, 2012, 52(5), 1319-1327.
101. Brunhofer, G.; Fallarero, A.; Karlsson, D.; Batista-Gonzalez, A.; Shinde, P.; Gopi Mohan, C; Vuorela, P. Exploration of natural compounds as sources of new bifunctional scaffolds targeting cho-linesterases and beta amyloid aggregation: the case of chel-erythrine. Bioorg. Med. Chem., 2012, 20(22), 6669-6679.
102. La Regina, G.; Silvestri, R.; Gatti, V.; Lavecchia, A.; Novellino, E.; Befani, O.; Turini, P.; Agostinelli, E. Synthesis, structure-activity relationships and molecular modeling studies of new indole inhibitors of monoamine oxidases A and B. Bioorg. Med. Chem., 2008, 16(22), 9729-9740.
103. Garcia, C.F.; Marco, J.L.; Alvarez, E.F. Synthesis of a- and pi-methyl derivatives of 2-[(5-methoxy-1-methyl)indol-2-yl]ethyl-amine as selective inhibitors of monoamine oxidases A and B. Tetrahedron, 1992, 48(33), 6917-6928.
104. Martin, L.L.; Davis, L.; Klein, J.T.; Nemoto, P.; Olsen, G.E.; Bores, G.M.; Camacho, F.P. W. W.; Rush, D.K.; Selk, D.; Smith, C.P.; Vargas, H.M.; Winslow, J.T.; Effland, R.C.; Fink, D.M., Synthesis and preliminary structure-activity relationships of 1-[(3-fluoro-4-pyridinyl)amino]-3-methyl-1H-indol-5-yl methyl carbamate (P10358), a novel acetylcholinesterase inhibitor. Bioog. Med. Chem. Lett., 1997, 7(2), 157-162.
105. Hadjipavlou-Litina, D.; Samadi, A.; Unzeta, M.; Marco-Contelles, J. Analysis of the antioxidant properties of differently substituted 2-and 3-indolyl carbohydrazides and related derivatives. Eur. J. Med. Chem., 2013, 63, 670-674.
106. Degterev, A.; Huang, Z.; Boyce, M.; Li, Y.; Jagtap, P.; Mizushima, N.; Cuny, G.D.; Mitchison, T.J.; Moskowitz, M.A.; Yuan, J. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat. Chem. Biol., 2005, 1(2), 112-119.
107. Degterev, A.; Hitomi, J.; Germscheid, M.; Ch'en, I.L.; Korkina, O.; Teng, X.; Abbott, D.; Cuny, G.D.; Yuan, C; Wagner, G.; Hedrick, S.M.; Gerber, S.A.; Lugovskoy, A.; Yuan, J. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat. Chem. Biol., 2008, 4(5), 313-321.
108. You, Z.; Savitz, S.I.; Yang, J.; Degterev, A.; Yuan, J.; Cuny, G.D.; Moskowitz, M.A.; Whalen, M.J. Necrostatin-1 reduces histopa-thology and improves functional outcome after controlled cortical impact in mice. J. Cereb. Blood Flow Metab., 2008, 28(9), 1564-1573.
109. Northington, F.J.; Chavez-Valdez, R.; Graham, E.M.; Razdan, S.; Gauda, E.B.; Martin, L.J. Necrostatin decreases oxidative damage, inflammation, and injury after neonatal HI. J. Cereb. Blood Flow Metab., 2011, 31(1), 178-189.
110. Youdim, M.B.; Wadia, A.; Tatton, W.; Weinstock, M. The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo. Ann. N Y Acad. Sci., 2001, 939, 450-458.
111. Bonnet, U.; Leniger, T.; Wiemann, M. Moclobemide reduces intracellular pH and neuronal activity of CA3 neurones in guinea-pig hippocampal slices-implication for its neuroprotective properties. Neuropharmacology, 2000, 39(11), 2067-2074.
112. Binda, C; Newton-Vinson, P.; Hubalek, F.; Edmondson, D.E.; Mattevi, A. Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders. Nat. Struct. Biol, 2002, 9(1), 22-26.
113. Binda, C; Wang, J.; Pisani, L.; Caccia, C; Carotti, A.; Salvati, P.; Edmondson, D.E.; Mattevi, A. Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safi-namide and coumarin analogs. J. Med. Chem., 2007, 50(23), 5848-5852.
114. Binda, C; Aldeco, M.; Mattevi, A.; Edmondson, D.E. Interactions of monoamine oxidases with the antiepileptic drug zonisamide: specificity of inhibition and structure of the human monoamine oxidase B complex. J. Med. Chem., 2011, 54(3), 909-912.