Synthesis, Molecular Docking, and Preliminary Evaluation of 2-(1,2,3-Triazoyl)benzaldehydes As Multifunctional Agents for the Treatment of Alzheimer's Disease.
Acetylcholinesterase
/ metabolism
Alzheimer Disease
/ chemically induced
Animals
Behavior, Animal
/ drug effects
Benzaldehydes
/ chemical synthesis
Cholinesterase Inhibitors
/ chemical synthesis
Disease Models, Animal
Male
Mice
Molecular Docking Simulation
Neuroprotective Agents
/ chemical synthesis
Streptozocin
1,2,3-triazoles
Alzheimer's disease
molecular docking
multitarget
thiourea
Journal
ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013
Informations de publication
Date de publication:
03 04 2020
03 04 2020
Historique:
received:
04
11
2019
revised:
20
01
2020
pubmed:
6
2
2020
medline:
10
4
2021
entrez:
4
2
2020
Statut:
ppublish
Résumé
We described here our results on the use of thiourea as a ligand in the copper catalysed azide-alkyne cycloaddition (CuAAC) of 2-azidobenzaldehyde with alkynes. Reactions were performed reacting 2-azidobenzaldehyde with a range of terminal alkynes using 10 mol % of copper iodide as a catalyst, 20 mol % of thiourea as a ligand, triethylamine as base, DMSO as solvent at 100 °C under nitrogen atmosphere. The corresponding 2-(1H-1,2,3-triazoyl)-benzaldehydes (2-TBH) were obtained in moderated to excellent yields and according our experiments, the use of thiourea decreases the formation of side products. The obtained compounds were screened for their binding affinity with multiple therapeutic targets of AD by molecular docking: β-secretase (BACE), glycogen synthase kinase (GSK-3β) and acetylcholinesterase (AChE). The three compounds with highest affinity, 5 a (2-(4-phenyl-1H-1,2,3-triazol-1-yl)benzaldehyde), 5 b (2-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)benzaldehyde), and 5 d (2-(4-(4-(tert-butyl)phenyl)-1H-1,2,3-triazol-1-yl)benzaldehyde) were selected and evaluated on its antioxidant effect, in view of select the most promising one to perform the in vivo validation. Due the antioxidant potential ally to the affinity with BACE, GSK-3β and AChE, compound 5 b was evaluated in a mouse model of AD induced by intracerebroventricular injection of streptozotocin (STZ). Our results indicate that 5 b (1 mg/kg) treatment during 20 days is able to reverse the cognitive and memory impairment induced by STZ trough the modulation of AChE activity, amyloid cascade and GSK-3β expression.
Identifiants
pubmed: 32012463
doi: 10.1002/cmdc.201900622
doi:
Substances chimiques
Benzaldehydes
0
Cholinesterase Inhibitors
0
Neuroprotective Agents
0
Streptozocin
5W494URQ81
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
610-622Informations de copyright
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Références
B. Halliwell, J. M. C. Gutteridge, Free Radical Biol. Med. 2007. doi:10.1016/0891-5849(91)90055-8.
J. C. Polanco, C. Li, L.-G. Bodea, R. Martinez-Marmol, F. A. Meunier, J. Götz, Nat. Rev. Neurol. 2018, 14, 22-39;
C. Cervellati, P. L. Wood, A. Romani, G. Valacchi, M. Squerzanti, J. M. Sanz, B. Ortolani, G. Zuliani, J. Invest. Med. 2016, 64, 21-32.
F. Prati, A. De Simone, P. Bisignano, A. Armirotti, M. Summa, D. Pizzirani, R. Scarpelli, D. I. Perez, V. Andrisano, A. Perez-Castillo, B. Monti, F. Massenzio, L. Polito, M. Racchi, A. D. Favia, G. Bottegoni, A. Martinez, M. L. Bolognesi, A. Cavalli, Angew. Chem. Int. Ed. 2014, 53, 1-6;
M. Cabrera, S. de Ovalle, M. Bollati-Fogolín, F. Nascimento, P. Corbelini, F. Janarelli, D. Kawano, V. L. Eifler-Lima, M. González, H. Cerecetto, Future Med. Chem. 2017, 3, 1-15.
M. Unzeta, G. Esteban, I. Bolea, W. A. Fogel, R. R. Ramsay, M. B. H. Youdim, K. F. Tipton, J. Marco-Contelles, Front. Neurol. Neurosci. 2016, 10, 1-24.
S. Agatonovic-Kustrin, C. Kettle, D. W. Morton, Biomed. Pharmacother. 2018, 106, 553-565;
M. G. Fronza, R. Baldinotti, M. C. Martins, B. Goldani, B. T. Dalberto, F. S. Kremer, K. Begnini, L. S. Pinto, E. J. Lenardão, F. K. Seixas, T. Collares, D. Alves, L. Savegnago, Sci. Rep. 2019, 9, 1-14.
M. E. Kelany, T. M. Hakami, A. H. Omar, M. A. Abdallah, Pharmacology 2016, 98, 242-250.
M. A. Farran, M. A. Bonet, R. M. Claramunt, M. C. Torralba, I. Alkorta, J. Elguero, Acta Crystallogr. Sect. C 2018, C74, 513-522.
A. Iraji, O. Firuzi, M. Khoshneviszadeh, M. Tavakkoli, M. Mahdavi, H. Nadri, N. Edraki, R. Miri, Eur. J. Med. Chem. 2017, 141, 690-702.
For a set of reviews in this area, see the themed issue:
Chem. Soc. Rev. 2010, 39, 1221-1408;
Accounts Chem. Res. 2011, 44, 651-840.
V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew. Chem. Int. Ed. 2002, 41, 2596-2599;
C. W. Tornøe, C. Christensen, M. Meldal, J. Org. Chem. 2002, 67, 3057-3064.
G. C. Tron, T. Pirali, R. A. Billington, P. L. Canonico, G. Sorba, A. A. Genazzani, Med. Res. Rev. 2008, 28, 278-308;
C. D. Hein, X.-M. Liu, D. Wang, Pharm. Res. 2008, 25, 2216-2230;
J. Xie, C. T. Seto, Bioorg. Med. Chem. 2007, 15, 458-473;
T. Lee, M. Cho, S. Y. Ko, H. J. Youn, D. J. Baek, W. J. Cho, C. Y. Kang, S. Kirn, J. Med. Chem. 2007, 50, 585-589;
B. Parrish, T. Emrick, Bioconjugate Chem. 2007, 18, 263-267;
A. M. Deobald, L. R. S. Camargo, D. Alves, J. Zukerman-Schpector, A. G. Correa, M. W. Paixão, Synthesis 2011, 24, 4003-4010;
A. Krasinski, Z. Radic, R. Manetsch, J. Raushel, P. Taylor, K. B. Sharpless, H. C. Kolb, J. Am. Chem. Soc. 2005, 127, 6686-6692;
L. V. Lee, M. L. Mitchell, S. Huang, V. V. Fokin, K. B. Sharpless, C. Wong, J. Am. Chem. Soc. 2003, 125, 9588-9589;
J. E. Hein, J. P. Tripp, L. B. Krasnova, K. B. Sharpless, V. V. Fokin, Angew. Chem. Int. Ed. 2009, 48, 8018-8021;
F. Fazio, M. C. Bryan, O. Blixt, J. C. Paulson, C.-H. Wong, J. Am. Chem. Soc. 2002, 124, 14397-14402.
W. S. Horne, C. D. Stout, M. R. Ghadiri, J. Am. Chem. Soc. 2003, 125, 9372-9376;
W. S. Horne, M. K. Yadav, C. D. Stout, M. R. Ghadiri, J. Am. Chem. Soc. 2004, 126, 15366-15367.
M. R. Grimett, In Comprehensive Organic Chemistry, Vol.3, Barton, Ollis, D., Eds.; Pergamon: Oxford, 1979, 77.
M. Aufort, J. Herscovici, P. Bouhours, N. Moreau, C. Girard, Bioorg. Med. Chem. Lett. 2008, 18, 1195-1198;
D. Pereira, P. Fernandes, Bioorg. Med. Chem. Lett. 2011, 21, 510-513.
R. G. Lima-Neto, N. N. M. Cavalcante, R. M. Srivastava, F. J. B. M. Junior, A. G. Wanderley, R. P. Neves, A. P. Anjos, Molecules 2012, 17, 5882-5892;
A. H. Kategaonkar, P. V. Shinde, A. H. Kategaonkar, S. K. Pasale, B. B. Shingate, M. S. Shingare, Eur. J. Med. Chem. 2010, 45, 3142-3146;
K. Shalini, N. Kumar, S. Drabu, Beilstein J. Org. Chem. 2011, 7, 668-677.
F. C. Silva, M. C. B. V. Souza, I. I. P. Frugulhetti, H. C. Castro, S. L. O. Souza, T. M. L. Souza, D. Q. Rodrigues, A. M. T. Souza, P. A. Abreu, F. Passamani, C. R. Rodrigues, V. F. Ferreira, Eur. J. Med. Chem. 2009, 44, 373-383;
M. Whiting, J. C. Tripp, Y.-C. Lin, W. Lindstrom, A. J. Olson, J. H. Elder, K. B. Sharpless, V. V. Fokin, J. Med. Chem. 2006, 49, 7697-7710;
D. J. Leaver, R. M. Dawson, J. M. White, A. Polyzos, A. B. Hughes, Org. Biomol. Chem. 2011, 9, 8465-8474.
C. Im, S. N. Maiti, R. G. Micetich, M. Daneshtalab, K. Atchison, O. A. Phillips, C. Kunugita, J. Antibiot. 1994, 47, 1030-1040.
W. Tong, J. C. Wu, A. Sandstrom, Tetrahedron 1990, 46, 3037-2060.
R. Raj, P. Singh, P. Singh, J. Gut, P. J. Rosenthal, V. Kumar, Eur. J. Med. Chem. 2013, 62, 590-596.
A. Dömling, Chem. Rev. 2006, 106, 17-89;
J. Zhu, H. Bienaymé, Multicomponent Reactions, Wiley-VCH, Weinheim, 2005;
V. Nair, C. Rajesh, A. U. Vinod, S. Bindu, A. R. Sreekenth, L. Balagopal, Acc. Chem. Res. 2003, 36, 899-907;
G. Balme, E. Bossharth, N. Monteiro, Eur. J. Org. Chem. 2003, 4101-4111;
A. Dömling, I. Ugi, Angew. Chem. Int. Ed. 2000, 39, 3168-3210;
H. Bienaymé, C. Hulme, G. Oddon, P. Schmitt, Chem. Eur. J. 2000, 6, 3321-3329.
M. Matloobi, C. O. Kappe, J. Comb. Chem. 2007, 9, 275-284;
D. S. Bose, L. Fatima, H. B. Mereyala, J. Org. Chem. 2003, 68, 587-590;
Y. Huang, F. Yang, C. Zhu, J. Am. Chem. Soc. 2005, 127, 16386-16387;
M. M. Heravi, M. Ghavidel, B. Heidari, Curr. Org. Synth. 2016, 13, 569-600;
H. Guo, C. Zhu, J. Li, G. Xu, J. Sun, Adv. Synth. Catal. 2014, 356, 2801-2806;
J. Pandey, N. Anand, R. P. Tripathi, Tetrahedron 2009, 65, 9350-9356.
F. Peringer, J. E. R. Nascimento, P. B. Abib, T. Barcellos, E. V. Van der Eycken, G. Perin, R. G. Jacob, D. Alves, Eur. J. Org. Chem. 2017, 2579-2586.
K. A. Dururgkar, R. G. Gonnade, C. V. Ramana, Tetrahedron 2009, 65, 3974-3979;
A. Hayeebueraheng, B. Kaewmee, V. Rukachaisirikul, J. Kaeobamrung, Eur. J. Org. Chem. 2017, 6714-6721;
R. Boobalan, C. Chen, G. Lee, Catal. Commun. 2018, 107, 33-38.
L. Mohammadi, M. A. Zolfigol, A. Khazaei, M. Yarie, S. Ansari, S. Azizian, M. Khosravi, Appl. Organomet. Chem. 2018, 32, e3933.
M. K. Barman, A. K. Sinha, S. Nembenna, Green Chem. 2016, 18, 2534-2541.
S. Wang, K. Jia, J. Cheng, Y. Chen, Y. Yuan, Tetrahedron Lett. 2017, 58, 3717-3721.
J. Kashanna, R. A. Kumar, R. Kishore, D. N. Kumar, A. S. Kumar, Chem. Biodiversity 2018, 15, e1800277.
F. Burcul, I. Blazevic, M. Radan, O. Politeo, Curr. Med. Chem. 2018. doi:10.2174/0929867325666180330092607.
Y.-H. Ko, S. Y. Kim, S.-Y. Lee, C.-G. Jang, Eur. J. Pharmacol. 2018, 826, 140-147.
C. Venugopal, C. M. Demos, K. S. J. Rao, M. A. Pappolla, K. Sambamurti, CNS Neurol. Disord. Drug Targets 2008, 7, 278-294.
O. Di Pietro, J. Juarez-Jimenez, D. Muñoz-Torrero, C. A. Laughton, F. J. Luque, PLoS One 2017, doi:10.1371/journal.pone.0177683.
A. K. Ghosh, H. L. Osswald, Chem. Soc. Rev. 2014, 43, 6765-6813.
M. Bajda, A. Wiéckowska, M. Hebda, N. Guzior, C. A. Sotriffer, B. Malawska, Int. J. Mol. Sci. 2013, 14, 5608-5632.
Z. Liang, Q. X. Li, ACS Chem. Neurosci. 2018, 9, 1166-1183.
G. V. Rayasam, V. K. Tulasi, R. Sodhi, J. A. Davis, A. Ray, Br. J. Pharmacol. 2009, 156, 885-898.
U. D. Özkay, Ö. D. Can, B. N. Sağlık, N. Turan, Pharmacol. Rep. 2017, 69, 1349-1356;
M. E. Sorial, N. S. E. D. E. Sayed, N.-S. Arch. Pharmacol. 2017, 6, 581-593.
T. Ponce-Lopez, E. Hong, M. Abascal-Díaz, A. Meneses, Adv. Alzheimers Dis. 2017, 6, 13-31;
A. M. E. Halawany, N. S. E. Sayed, H. M. Abdallah, R. S. E. Dine, Sci. Rep. 2017, 7, 2902-2913.
R. Yan, Q. Fan, J. Zhou, R. Vassar, Neurosci. Biobehav. Rev. 2016, 65, 326-340;
G. Evin, BioDrugs 2016, 30, 173-194.
R. Yan, Stepping closer to treating Alzheimer's disease patients with BACE1 inhibitor drugs, Vol. 5, Translational Neurodegeneration. London; 2016.
V. Volloch, S. Rits, Med. Sci. 2018, 6, 45-58.
A. Contestabile, Behav. Brain Res. 2011, 221, 334-340;
T. H. Ferreira-Vieira, I. M. Guimaraes, F. R. Silva, F. M. Ribeiro, Curr. Neuropharmacol. 2016, 14, 101-115.
D. B. Hogan, Can. J. Phys. 2014, 59, 618-623.
S. Gupta, C. G. Mohan, BioMed Res. Int. 2014, 291214.
Z. Liu, T. Li, P. Li, N. Wei, Z. Zhao, H. Liang, X. Ji, W. Chen, M. Xue, J. Wei, Oxid. Med. Cell. Longev. 2015, 352723.
A. Lloret, T. Fuchsberger, E. Giraldo, J. Vina, Free Radical Biol. Med. 2015, 83, 186-191;
P. K. Kamat, A. Kalani, S. Rai, S. Swarnkar, S. Tota, C. Nath, N. Tyagi, Mol. Neurobiol. 2016, 53, 648-661.
M. Llorens-Marítin, J. Jurado, F. Hernández, J. Ávila, Front. Neurol. Neurosci. 2014, 7, 1-11.
J. Folch, D. Petrov, M. Ettcheto, S. Abad, E. Sanchez-Lopez, M. L. Garcia, J. Olloquequi, C. Beas-Zarate, C. Auladell, A. Camins, Neural Plast. 2016, 8501693.
D. J. Diller, J. Swanson, A. S. Bayden, M. Jarosinski, J. Audie, Future Med. Chem. 2015, 7, 2173-2193;
C.-L. Hung, C.-C. Chen, Drug Dev. Res. 2014, 75, 412-418.
M. D. Hanwell, D. E. Curtis, D. C. Lonie, T. Vandermeerschd, E. Zurek, G. R. Hutchison, J. Cheminf. 2012, 4, doi:10.1186/1758-2946-4-17.
E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenblatt, E. C. Meng, T. E. Ferrin, J. Comput. Chem. 2004, 25, 1605-1612.
O. Trott, A. J. Olson, J. Comput. Chem. 2010, 31, 455-461.
H. Ohkawa, N. Ohishi, K. Yagi, Anal. Biochem. 1979, 95, 351-358.
C. Loetchutinat, S. Kothan, S. Dechsupa, J. Meesungnoen, J. P. Jay-Gerin, S. Mankhetkorn, Radiat. Phys. Chem. 2005, 72, 323-331.
G. L. Ellman, K. D. Courtney, V. Andres, R. M. Feather-Stone, Biochem. Pharmacol. 1961, 7, 88-95.
T. j Haley, W. G. Mccormick, Br. J. Pharmacol. Chemother. 1957, 12, 12-15;
S. E. Laursen, J. K. Belknap, J. Pharmacol. Methods 1986, 16, 355-357.
R. N. Walsh, R. Cummins, Psychopharmacol. Bull. 1976, 83, 482-504.
R. M. Rosa, D. G. Flores, H. R. Appelt, A. L. Braga, J. A. P. Henriques, R. Roesler, Neurosci. Lett. 2003, 341, 217-220.
L. L. Jackson, J. Comp. Psychol. 1943, 99-107.