Versatility of the Curcumin Scaffold: Discovery of Potent and Balanced Dual BACE-1 and GSK-3β Inhibitors

Journal of Medicinal Chemistry

Volumn 59, Issue 2, 2016, Pages 531-544

  Di Martino, Rita Maria Concetta ^a   De Simone, Angela ^a   Andrisano, Vincenza ^a   Bisignano, Paola ^b   Bisi, Alessandra ^a   Gobbi, Silvia ^a   Rampa, Angela ^a   Fato, Romana ^a   Bergamini, Christian ^a   Perez, Daniel I ^c   Martinez, Ana ^c   Bottegoni, Giovanni ^b   Cavalli, Andrea ^a,b   Belluti, Federica ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

^c CENTRO DE INVESTIGACIONES BIOLÓGICAS   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

1 (4 BENZYLOXYPHENYL) 5 HYDROXY 7 (4 HYDROXY 3 METHOXYPHENYL)HEPTA 1,4,6 TRIEN 3 ONE; 1,7 BIS 4 ( 2,4 DIFLUOROBENZYLOXYPHENYL)HEPTA 1,6 DIENE 3,5 DIONE; 1,7 BIS 4 (3 FLUOROBENZYLOXYPHENYL) 5 HYDROXYHEPTA 1,4,6 TRIEN 3 ONE; 1,7 BIS 4 (3,5 DIFLUOROBENZYLOXYPHENYL) 5 HYDROXYHEPTA 1,4,6 TRIEN 3 ONE; 1,7 BIS 4 (3,5 DIFLUOROBENZYLOXYPHENYL)HEPTA 1,6 DIENE 3,5 DIONE; 1,7 BIS 4 (4 FLUOROBENZYLOXYPHENYL) 5 HYDROXYHEPTA 1,4,6 TRIEN 3 ONE; 1,7 BIS 4 BENZYLOXYPHENYL 5 HYDROXYHEPTA 1,4,6 TRIEN 3 ONE; 1,7 BIS 4 BENZYLOXYPHENYLHEPTA 1,6 DIENE 3,5 DIONE; 1,7 BIS 4 METHOXYPHENYLHEPTA 1,6 DIENE 3,5 DIONE; 4 (3 FLUOROBENZYLOXY)BENZALDEHYDE; 4 (4 FLUOROBENZYLOXY)BENZALDEHYDE; 4 HYDROXY 6 (4 HYDROXY 3 METHOXYPHENYL)HEXA 3,5 DIEN 2 ONE; 5 HYDROXY 1,7 BIS 4 HYDROXYPHENYLHEPTA 1,4,6 TRIEN 3 ONE; 5 HYDROXY 1,7 BIS 4 METHOXYPHENYLHEPTA 1,4,6 TRIEN 3 ONE; 5 HYDROXY 7 (4 HYDROXY 3 METHOXYPHENYL) 1 P TOLYLHEPTA 1,4,6 TRIEN 3 ONE; 6 (4 BENZYLOXYPHENYL) 4 HYDROXYHEXA 3,5 DIEN 2 ONE; 7 (4 BENZYLOXYPHENYL) 5 HYDROXY 1-4 HYDROXYPHENYLHEPTA 1,4,6 TRIEN 3 ONE; 7 (4 BENZYLOXYPHENYL) 5 HYDROXY 1-4 METHOXYPHENYLHEPTA 1,4,6 TRIEN 3 ONE; ANTIOXIDANT; ASPARTIC PROTEINASE INHIBITOR; CURCUMIN; NEUROPROTECTIVE AGENT; PROTEIN SERINE THREONINE KINASE INHIBITOR; UNCLASSIFIED DRUG; AMYLOID BETA PROTEIN; ASPARTIC PROTEINASE; BACE1 PROTEIN, HUMAN; ENZYME INHIBITOR; GLYCOGEN SYNTHASE KINASE 3; GLYCOGEN SYNTHASE KINASE 3 BETA; MOLECULAR LIBRARY; NQO1 PROTEIN, HUMAN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); SECRETASE;

ALZHEIMER DISEASE; ANTIOXIDANT ACTIVITY; ARTICLE; BLOOD BRAIN BARRIER; BRAIN; CELL VIABILITY; CONTROLLED STUDY; DRUG PENETRATION; DRUG POTENCY; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INHIBITION; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMAN; HUMAN CELL; IC50; METABOLIC STABILITY; MOLECULAR DOCKING; NEUROPROTECTION; NUCLEOPHILICITY; OXIDATIVE STRESS; PHARMACOPHORE; PROTON NUCLEAR MAGNETIC RESONANCE; TAUTOMER; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CELL SURVIVAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; DRUG EFFECTS; ENZYME INDUCTION; METABOLISM; MOLECULAR LIBRARY; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TUMOR CELL LINE;

AMYLOID BETA-PEPTIDES; AMYLOID PRECURSOR PROTEIN SECRETASES; ASPARTIC ACID ENDOPEPTIDASES; BLOOD-BRAIN BARRIER; BRAIN; CELL LINE, TUMOR; CELL SURVIVAL; CURCUMIN; DRUG DESIGN; ENZYME INDUCTION; ENZYME INHIBITORS; GLYCOGEN SYNTHASE KINASE 3; HUMANS; MODELS, MOLECULAR; MOLECULAR DOCKING SIMULATION; NAD(P)H DEHYDROGENASE (QUINONE); NEUROPROTECTIVE AGENTS; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84964297885     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00894     Document Type: Article

References (69)

1. Dulsat, C. A report from the 65th Annual Meeting of the American Academy of Neurology (March 16-23, 2013, San Diego, California, USA) Drugs Today (Barc) 2013, 49 (5) 341-5 10.1358/dot.2013.49.5.1976050
2. Cummings, J. L. Treatment of Alzheimeŕs disease: current and future therapeutic approaches Rev. Neuro.l Dis. 2004, 1 (2) 60-69
3. Lazarov, O.; Marr, R. A. Neurogenesis and Alzheimeŕs disease: at the crossroads Exp. Neurol. 2010, 223 (2) 267-281 10.1016/j.expneurol.2009.08.009
4. Marx, J. A New Take on Tau Science 2007, 316 (5830) 1416-1417 10.1126/science.316.5830.1416
5. Walsh, D. M.; Selkoe, D. J. Deciphering the molecular basis of memory failure in Alzheimeŕs disease Neuron 2004, 44 (1) 181-193 10.1016/j.neuron.2004.09.010
6. Schneider, L. S.; Mangialasche, F.; Andreasen, N.; Feldman, H.; Giacobini, E.; Jones, R.; Mantua, V.; Mecocci, P.; Pani, L.; Winblad, B.; Kivipelto, M. Clinical trials and late-stage drug development for Alzheimeŕs disease: an appraisal from 1984 to 2014 J. Intern. Med. 2014, 275 (3) 251-283 10.1111/joim.12191
7. Golde, T. E.; Eckman, C. B.; Younkin, S. G. Biochemical detection of Abeta isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimeŕs disease Biochim. Biophys. Acta, Mol. Basis Dis. 2000, 1502 (1) 172-187 10.1016/S0925-4439(00)00043-0
8. Golde, T. E. Alzheimer disease therapy: can the amyloid cascade be halted? J. Clin. Invest. 2003, 111 (1) 11-18 10.1172/JCI200317527
9. Tamagno, E.; Bardini, P.; Obbili, A.; Vitali, A.; Borghi, R.; Zaccheo, D.; Pronzato, M. A.; Danni, O.; Smith, M. A.; Perry, G.; Tabaton, M. Oxidative stress increases expression and activity of BACE in NT2 neurons Neurobiol. Dis. 2002, 10 (3) 279-288 10.1006/nbdi.2002.0515
10. Ghosh, A. K.; Gemma, S.; Tang, J. beta-secretase as a therapeutic target for Alzheimeŕs disease Neurotherapeutics 2008, 5 (3) 399-408 10.1016/j.nurt.2008.05.007
11. Ittner, L. M.; Götz, J. Amyloid-β and tau - a toxic pas de deux in Alzheimeŕs disease Nat. Rev. Neurosci. 2011, 12 (2) 65-72 10.1038/nrn2967
12. Weingarten, M. D.; Lockwood, A. H.; Hwo, S. Y.; Kirschner, M. W. A protein factor essential for microtubule assembly Proc. Natl. Acad. Sci. U. S. A. 1975, 72 (5) 1858-1862 10.1073/pnas.72.5.1858
13. Avila, J. Tau phosphorylation and aggregation in Alzheimeŕs disease pathology FEBS Lett. 2006, 580 (12) 2922-2927 10.1016/j.febslet.2006.02.067
14. Llorens-Martín, M.; Jurado, J.; Hernández, F.; Avila, J. GSK-3β, a pivotal kinase in Alzheimer disease Front. Mol. Neurosci. 2014, 7, 46 10.3389/fnmol.2014.00046
15. Billingsley, M. L.; Kincaid, R. L. Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration Biochem. J. 1997, 323 (Pt 3) 577-591 10.1042/bj3230577
16. Martinez, A.; Perez, D. I.; Gil, C. Lessons learnt from glycogen synthase kinase 3 inhibitors development for Alzheimeŕs disease Curr. Top. Med. Chem. 2013, 13 (15) 1808-1819 10.2174/15680266113139990138
17. Perez, D. I.; Conde, S.; Perez, C.; Gil, C.; Simon, D.; Wandosell, F.; Moreno, F. J.; Gelpi, J. L.; Luque, F. J.; Martinez, A. Thienylhalomethylketones: Irreversible glycogen synthase kinase 3 inhibitors as useful pharmacological tools Bioorg. Med. Chem. 2009, 17 (19) 6914-6925 10.1016/j.bmc.2009.08.042
18. Perez, D. I.; Palomo, V.; Perez, C.; Gil, C.; Dans, P. D.; Luque, F. J.; Conde, S.; Martinez, A. Switching Reversibility to Irreversibility in Glycogen Synthase Kinase 3 Inhibitors: Clues for Specific Design of New Compounds J. Med. Chem. 2011, 54 (12) 4042-4056 10.1021/jm1016279
19. Perez, D. I.; Palomo, V.; Perez, C.; Gil, C.; Dans, P. D.; Luque, F. J.; Conde, S.; Martinez, A. Switching Reversibility to Irreversibility in Glycogen Synthase Kinase 3 Inhibitors: Clues for Specific Design of New Compounds J. Med. Chem. 2011, 54 (12) 4042-4056 10.1021/jm1016279
20. Busciglio, J.; Lorenzo, A.; Yeh, J.; Yankner, B. A. beta-amyloid fibrils induce tau phosphorylation and loss of microtubule binding Neuron 1995, 14 (4) 879-888 10.1016/0896-6273(95)90232-5
21. Zheng, W. H.; Bastianetto, S.; Mennicken, F.; Ma, W.; Kar, S. Amyloid beta peptide induces tau phosphorylation and loss of cholinergic neurons in rat primary septal cultures Neuroscience 2002, 115 (1) 201-211 10.1016/S0306-4522(02)00404-9
22. Golde, T. E. Disease modifying therapy for AD? J. Neurochem. 2006, 99 (3) 689-707 10.1111/j.1471-4159.2006.04211.x
23. Grill, J. D.; Cummings, J. L. Current therapeutic targets for the treatment of Alzheimeŕs disease Expert Rev. Neurother. 2010, 10 (5) 711-728 10.1586/ern.10.29
24. 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) 347-72 10.1021/jm7009364
25. Viayna, E.; Sola, I.; Di Pietro, O.; Muńoz-Torrero, D. Human disease and drug pharmacology, complex as real life Curr. Med. Chem. 2013, 20 (13) 1623-1634 10.2174/0929867311320130002
26. Zheng, H.; Fridkin, M.; Youdim, M. From single target to multitarget/network therapeutics in Alzheimeŕs therapy Pharmaceuticals 2014, 7 (2) 113-135 10.3390/ph7020113
27. Morphy, R.; Kay, C.; Rankovic, Z. From magic bullets to designed multiple ligands Drug Discovery Today 2004, 9 (15) 641-651 10.1016/S1359-6446(04)03163-0
28. Prati, F.; De Simone, A.; Bisignano, P.; Armirotti, A.; Summa, M.; Pizzirani, D.; Scarpelli, R.; Perez, D. I.; Andrisano, V.; Perez-Castillo, A.; Monti, B.; Massenzio, F.; Polito, L.; Racchi, M.; Favia, A. D.; Bottegoni, G.; Martinez, A.; Bolognesi, M. L.; Cavalli, A. Multitarget drug discovery for Alzheimeŕs disease: triazinones as BACE-1 and GSK-3β inhibitors Angew. Chem., Int. Ed. 2015, 54 (5) 1578-1582 10.1002/anie.201410456
29. Belluti, F.; De Simone, A.; Tarozzi, A.; Bartolini, M.; Djemil, A.; Bisi, A.; Gobbi, S.; Montanari, S.; Cavalli, A.; Andrisano, V.; Bottegoni, G.; Rampa, A. Fluorinated benzophenone derivatives: balanced multipotent agents for Alzheimeŕs disease Eur. J. Med. Chem. 2014, 78, 157-166 10.1016/j.ejmech.2014.03.042
30. Rizzo, S.; Tarozzi, A.; Bartolini, M.; Da Costa, G.; Bisi, A.; Gobbi, S.; Belluti, F.; Ligresti, A.; Allara, M.; Monti, J. P.; Andrisano, V.; Di Marzo, V.; Hrelia, P.; Rampa, A. 2-Arylbenzofuran-based molecules as multipotent Alzheimeŕs disease modifying agents Eur. J. Med. Chem. 2012, 58, 519-532 10.1016/j.ejmech.2012.10.045
31. Newman, D. J.; Cragg, G. M.; Snader, K. M. Natural products as sources of new drugs over the period 1981-2002 J. Nat. Prod. 2003, 66 (7) 1022-1037 10.1021/np030096l
32. Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.; Freidinger, R. M.; Whitter, W. L.; Lundell, G. F.; Veber, D. F.; Anderson, P. S. Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists J. Med. Chem. 1988, 31 (12) 2235-2246 10.1021/jm00120a002
33. Aggarwal, B. B.; Sundaram, C.; Malani, N.; Ichikawa, H. Curcumin: the Indian solid gold Adv. Exp. Med. Biol. 2007, 595, 1-75 10.1007/978-0-387-46401-5
34. Prasad, S.; Gupta, S. C.; Tyagi, A. K.; Aggarwal, B. B. Curcumin, a component of golden spice: from bedside to bench and back Biotechnol. Adv. 2014, 32 (6) 1053-1064 10.1016/j.biotechadv.2014.04.004
35. Anand, P.; Thomas, S. G.; Kunnumakkara, A. B.; Sundaram, C.; Harikumar, K. B.; Sung, B.; Tharakan, S. T.; Misra, K.; Priyadarsini, I. K.; Rajasekharan, K. N.; Aggarwal, B. B. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature Biochem. Pharmacol. 2008, 76 (11) 1590-1611 10.1016/j.bcp.2008.08.008
36. Chin, D.; Huebbe, P.; Pallauf, K.; Rimbach, G. Neuroprotective Properties of Curcumin in Alzheimeŕs Disease-Merits and Limitations Curr. Med. Chem. 2013, 20 (32) 3955-3985 10.2174/09298673113209990210
37. Esatbeyoglu, T.; Huebbe, P.; Ernst, I. M.; Chin, D.; Wagner, A. E.; Rimbach, G. Curcumin - from molecule to biological function Angew. Chem., Int. Ed. 2012, 51 (22) 5308-5332 10.1002/anie.201107724
38. Payton, F.; Sandusky, P.; Alworth, W. L. NMR study of the solution structure of curcumin J. Nat. Prod. 2007, 70 (2) 143-146 10.1021/np060263s
39. Benassi, R.; Ferrari, E.; Lazzari, S.; Spagnolo, F.; Saladini, M. Theoretical study on Curcumin: A comparison of calculated spectroscopic properties with NMR, UV-vis and IR experimental data J. Mol. Struct. 2008, 892 (1-3) 168-176 10.1016/j.molstruc.2008.05.024
40. Amslinger, S. The tunable functionality of alpha,beta-unsaturated carbonyl compounds enables their differential application in biological systems ChemMedChem 2010, 5 (3) 351-356 10.1002/cmdc.200900499
41. Bustanji, Y.; Taha, M. O.; Almasri, I. M.; Al-Ghussein, M. A.; Mohammad, M. K.; Alkhatib, H. S. Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation J. Enz. Inhib. Med. Chem. 2009, 24 (3) 771-778 10.1080/14756360802364377
42. Wang, X.; Kim, J. R.; Lee, S. B.; Kim, Y. J.; Jung, M. Y.; Kwon, H. W.; Ahn, Y. J. Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimeŕs disease Drosophila models BMC Complementary Altern. Med. 2014, 14, 88 10.1186/1472-6882-14-88
43. Pabon, H. J. A synthesis of curcumin and related compounds Recl. Trav. Chim. Pays-Bas 1964, 83, 379-386 10.1002/recl.19640830407
44. Mancini, F.; De Simone, A.; Andrisano, V. Beta-secretase as a target for Alzheimeŕs disease drug discovery: an overview of in vitro methods for characterization of inhibitors Anal. Bioanal. Chem. 2011, 400 (7) 1979-1996 10.1007/s00216-011-4963-x
45. Hagmann, W. K. The many roles for fluorine in medicinal chemistry J. Med. Chem. 2008, 51 (15) 4359-4369 10.1021/jm800219f
46. Silvestri, R. Boom in the development of non-peptidic beta-secretase (BACE1) inhibitors for the treatment of Alzheimeŕs disease Med. Res. Rev. 2009, 29 (2) 295-338 10.1002/med.20132
47. Baki, A.; Bielik, A.; Molnár, L.; Szendrei, G.; Keserü, G. M. A high throughput luminescent assay for glycogen synthase kinase-3beta inhibitors Assay Drug Dev. Technol. 2007, 5 (1) 75-83 10.1089/adt.2006.029
48. London, N.; Miller, R. M.; Krishnan, S.; Uchida, K.; Irwin, J. J.; Eidam, O.; Gibold, L.; Cimermančič, P.; Bonnet, R.; Shoichet, B. K.; Taunton, J. Covalent docking of large libraries for the discovery of chemical probes Nat. Chem. Biol. 2014, 10 (12) 1066-1072 10.1038/nchembio.1666
49. Minassi, A.; Sánchez-Duffhues, G.; Collado, J. A.; Muńoz, E.; Appendino, G. Dissecting the pharmacophore of curcumin. Which structural element is critical for which action? J. Nat. Prod. 2013, 76 (6) 1105-1112 10.1021/np400148e
50. Avonto, C.; Taglialatela-Scafati, O.; Pollastro, F.; Minassi, A.; Di Marzo, V.; De Petrocellis, L.; Appendino, G. An NMR spectroscopic method to identify and classify thiol-trapping agents: revival of Michael acceptors for drug discovery? Angew. Chem., Int. Ed. 2011, 50 (2) 467-471 10.1002/anie.201005959
51. Wang, Y. J.; Pan, M. H.; Cheng, A. L.; Lin, L. I.; Ho, Y. S.; Hsieh, C. Y.; Lin, J. K. Stability of curcumin in buffer solutions and characterization of its degradation products J. Pharm. Biomed. Anal. 1997, 15 (12) 1867-1876 10.1016/S0731-7085(96)02024-9
52. Dahmke, I. N.; Boettcher, S. P.; Groh, M.; Mahlknecht, U. Cooking enhances curcumin anti-cancerogenic activity through pyrolytic formation of 'deketene curcumin' Food Chem. 2014, 151, 514-519 10.1016/j.foodchem.2013.11.102
53. Cardoso, F. L.; Brites, D.; Brito, M. A. Looking at the blood-brain barrier: molecular anatomy and possible investigation approaches Brain Res. Rev. 2010, 64 (2) 328-363 10.1016/j.brainresrev.2010.05.003
54. van Asperen, J.; Mayer, U.; van Tellingen, O.; Beijnen, J. H. The functional role of P-glycoprotein in the blood-brain barrier J. Pharm. Sci. 1997, 86 (8) 881-884 10.1021/js9701364
55. Begum, A. N.; Jones, M. R.; Lim, G. P.; Morihara, T.; Kim, P.; Heath, D. D.; Rock, C. L.; Pruitt, M. A.; Yang, F.; Hudspeth, B.; Hu, S.; Faull, K. F.; Teter, B.; Cole, G. M.; Frautschy, S. A. Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimeŕs disease J. Pharmacol. Exp. Ther. 2008, 326 (1) 196-208 10.1124/jpet.108.137455
56. Di, L.; Kerns, E. H.; Fan, K.; McConnell, O. J.; Carter, G. T. High throughput artificial membrane permeability assay for blood-brain barrier Eur. J. Med. Chem. 2003, 38 (3) 223-232 10.1016/S0223-5234(03)00012-6
57. Crivori, P.; Cruciani, G.; Carrupt, P. A.; Testa, B. Predicting blood-brain barrier permeation from three-dimensional molecular structure J. Med. Chem. 2000, 43 (11) 2204-2216 10.1021/jm990968+
58. Zhu, X.; Su, B.; Wang, X.; Smith, M. A.; Perry, G. Causes of oxidative stress in Alzheimer disease Cell. Mol. Life Sci. 2007, 64 (17) 2202-2210 10.1007/s00018-007-7218-4
59. Siegel, D.; Gustafson, D. L.; Dehn, D. L.; Han, J. Y.; Boonchoong, P.; Berliner, L. J.; Ross, D. NAD(P)H:quinone oxidoreductase 1: role as a superoxide scavenger Mol. Pharmacol. 2004, 65 (5) 1238-1247 10.1124/mol.65.5.1238
60. Torres-Lista, V.; Parrado-Fernández, C.; Alvarez-Montón, I.; Frontińán-Rubio, J.; Durán-Prado, M.; Peinado, J. R.; Johansson, B.; Alcaín, F. J.; Giménez-Llort, L. Neophobia, NQO1 and SIRT1 as premorbid and prodromal indicators of AD in 3xTg-AD mice Behav. Brain Res. 2014, 271, 140-146 10.1016/j.bbr.2014.04.055
61. Tsvetkov, P.; Asher, G.; Reiss, V.; Shaul, Y.; Sachs, L.; Lotern, J. Inhibition of NAD(P)H: quinone oxidoreductase 1 activity and induction of p53 degradation by the natural phenolic compound curcumin Proc. Natl. Acad. Sci. U. S. A. 2005, 102 (15) 5535-5540 10.1073/pnas.0501828102
62. Capurro, V.; Busquet, P.; Lopes, J. P.; Bertorelli, R.; Tarozzo, G.; Bolognesi, M. L.; Piomelli, D.; Reggiani, A.; Cavalli, A. Pharmacological characterization of memoquin, a multi-target compound for the treatment of Alzheimeŕs disease PLoS One 2013, 8 (2) e56870 10.1371/journal.pone.0056870
63. Manson, M. M. Inhibition of survival signalling by dietary polyphenols and indole-3-carbinol Eur. J. Cancer 2005, 41 (13) 1842-1853 10.1016/j.ejca.2005.05.008
64. Lin, L.; Shi, Q.; Nyarko, A. K.; Bastow, K. F.; Wu, C. C.; Su, C. Y.; Shih, C. C.; Lee, K. H. Antitumor agents. 250. Design and synthesis of new curcumin analogues as potential anti-prostate cancer agents J. Med. Chem. 2006, 49 (13) 3963-3972 10.1021/jm051043z
65. Saladini, M.; Lazzari, S.; Pignedoli, F.; Rosa, R.; Spagnolo, F.; Ferrari, E. New synthetic glucosyl-curcuminoids, and their (1)H and (13)C NMR characterization, from Curcuma longa L Plant Foods Hum. Nutr. 2009, 64 (3) 224-229 10.1007/s11130-009-0122-3
66. Coghlan, M. P.; Culbert, A. A.; Cross, D. A.; Corcoran, S. L.; Yates, J. W.; Pearce, N. J.; Rausch, O. L.; Murphy, G. J.; Carter, P. S.; Roxbee Cox, L.; Mills, D.; Brown, M. J.; Haigh, D.; Ward, R. W.; Smith, D. G.; Murray, K. J.; Reith, A. D.; Holder, J. C. Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription Chem. Biol. 2000, 7 (10) 793-803 10.1016/S1074-5521(00)00025-9
67. Abagyan, R.; Raush, E.; Totrov, M. ICM Manual v.3.7. http://www.molsoft.com/man/index.html.
68. Jia, Z.; Zhu, H.; Misra, H. P.; Li, Y. Potent induction of total cellular GSH and NQO1 as well as mitochondrial GSH by 3H-1,2-dithiole-3-thione in SH-SY5Y neuroblastoma cells and primary human neurons: protection against neurocytotoxicity elicited by dopamine, 6-hydroxydopamine, 4-hydroxy-2-nonenal, or hydrogen peroxide Brain Res. 2008, 1197, 159-169 10.1016/j.brainres.2007.12.044
69. 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