Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Curcumin, Resveratrol and Cannabidiol as Natural Key Prototypes in Drug Design for Neuroprotective Agents

Author(s): Flávia P. Dias Viegas, Vanessa Silva Gontijo, Matheus de Freitas Silva, Cindy Juliet Cristancho Ortiz, Graziella dos Reis Rosa Franco, Januário Tomás Ernesto, Caio Miranda Damasio, Isabela Marie Fernandes Silva, Thâmara Gaspar Campos and Claudio Viegas*

Volume 20, Issue 7, 2022

Published on: 01 April, 2022

Page: [1297 - 1328] Pages: 32

DOI: 10.2174/1570159X19666210712152532

Price: $65

Abstract

Nowadays, neurodegenerative diseases (NDs), such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), represent a great challenge in different scientific fields, such as neuropharmacology, medicinal chemistry, molecular biology and medicine, as all these pathologies remain incurable, with high socioeconomic impacts and high costs for governmental health services. Due to their severity and multifactorial pathophysiological complexity, the available approved drugs for clinic have not yet shown adequate effectiveness and exhibited very restricted options in the therapeutic arsenal; this highlights the need for continued drug discovery efforts in the academia and industry. In this context, natural products, such as curcumin (1), resveratrol (2) and cannabidiol (CBD, 3) have been recognized as important sources, with promising chemical entities, prototype models and starting materials for medicinal organic chemistry, as their molecular architecture, multifunctional properties and single chemical diversity could facilitate the discovery, optimization and development of innovative drug candidates with improved pharmacodynamics and pharmacokinetics compared to the known drugs and, perhaps, provide a chance for discovering novel effective drugs to combat NDs. In this review, we report the most recent efforts of medicinal chemists worldwide devoted to the exploration of curcumin (1), resveratrol (2) and cannabidiol (CBD, 3) as starting materials or privileged scaffolds in the design of multi-target directed ligands (MTDLs) with potential therapeutic properties against NDs, which have been published in the scientific literature during the last 10 years of research and are available in PubMed, SCOPUS and Web of Science databases.

Keywords: Neuroprotection, neurodegenerative diseases, curcumin, resveratrol, cannabidiol, rational drug design, molecular hybridization.

Graphical Abstract

[1]
Bolognesi ML, Matera R, Minarini A, Rosini M, Melchiorre C. Alzheimer’s disease: new approaches to drug discovery. Curr Opin Chem Biol 2009; 13(3): 303-8.
[http://dx.doi.org/10.1016/j.cbpa.2009.04.619] [PMID: 19467915]
[2]
Youdim MBH, Buccafusco JJ. Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders. Trends Pharmacol Sci 2005; 26(1): 27-35.
[http://dx.doi.org/10.1016/j.tips.2004.11.007] [PMID: 15629202]
[3]
Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med 2004; 10(S7)(Suppl.): S10-7.
[http://dx.doi.org/10.1038/nm1066] [PMID: 15272267]
[4]
Association A. 2011 Alzheimer’s disease facts and figures. Alzheimers Dement 2011; 7(2): 208-44.
[http://dx.doi.org/10.1016/j.jalz.2011.02.004] [PMID: 21414557]
[5]
Dementia statistics | Alzheimer’s Disease International (ADI). 2011.
[6]
Manssour Fraga Ca, Barreiro EJ. New insights for multifactorial disease therapy: The challenge of the symbiotic drugs. Curr Drug Ther 2008; 3(1): 1-13.
[http://dx.doi.org/10.2174/157488508783331225]
[7]
Zhang H-Y. One-compound-multiple-targets strategy to combat Alzheimer’s disease. FEBS Lett 2005; 579(24): 5260-4.
[http://dx.doi.org/10.1016/j.febslet.2005.09.006] [PMID: 16194540]
[8]
Mattson MP, Magnus T. Ageing and neuronal vulnerability. Nat Rev Neurosci 2006; 7(4): 278-94.
[http://dx.doi.org/10.1038/nrn1886] [PMID: 16552414]
[9]
Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers 2017; 3: 17013.
[http://dx.doi.org/10.1038/nrdp.2017.13] [PMID: 28332488]
[10]
Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci 2015; 16(6): 358-72.
[http://dx.doi.org/10.1038/nrn3880] [PMID: 25991443]
[11]
Alzheimer’s Facts and Figures Report | Alzheimer’s Association. 2011.
[12]
Aspectos socioeconômicos | AlzheimerMed. 2011.
[13]
Gitler AD, Dhillon P, Shorter J. Neurodegenerative disease: models, mechanisms, and a new hope. Dis Model Mech 2017; 10(5): 499-502.
[http://dx.doi.org/10.1242/dmm.030205] [PMID: 28468935]
[14]
Pozo Devoto VM, Falzone TL. Mitochondrial dynamics in Parkinson’s disease: A role for α-synuclein? Dis Model Mech 2017; 10(9): 1075-87.
[http://dx.doi.org/10.1242/dmm.026294] [PMID: 28883016]
[15]
Amyotrophic Lateral Sclerosis (ALS) Fact Sheet | National Institute of Neurological Disorders and Stroke. 2011.
[16]
Jiang F, Zhang ZG, Katakowski M, et al. Angiogenesis induced by photodynamic therapy in normal rat brains. Photochem Photobiol 2004; 79(6): 494-8.
[http://dx.doi.org/10.1562/2003-11-19-RC.1] [PMID: 15291298]
[17]
Maulik N, Das DK. Redox signaling in vascular angiogenesis. Free Radic Biol Med 2002; 33(8): 1047-60.
[http://dx.doi.org/10.1016/S0891-5849(02)01005-5] [PMID: 12374616]
[18]
Calabrese V, Cornelius C, Dinkova-Kostova AT, Calabrese EJ, Mattson MP. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid Redox Signal 2010; 13(11): 1763-811.
[http://dx.doi.org/10.1089/ars.2009.3074] [PMID: 20446769]
[19]
Siracusa R, Scuto M, Fusco R, et al. Anti-inflammatory and Anti-oxidant Activity of Hidrox® in Rotenone-Induced Parkinson’s Disease in Mice. Antioxidants 2020; 9(9): 1-19.
[http://dx.doi.org/10.3390/antiox9090824] [PMID: 32899274]
[20]
Viegas-Junior C, Danuello A, da Silva Bolzani V, Barreiro EJ, Fraga CA. Molecular hybridization: A useful tool in the design of new drug prototypes. Curr Med Chem 2007; 14(17): 1829-52.
[http://dx.doi.org/10.2174/092986707781058805] [PMID: 17627520]
[21]
Marucci G, Buccioni M, Ben DD, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmacology 2021; 190: 108352.
[http://dx.doi.org/10.1016/j.neuropharm.2020.108352] [PMID: 33035532]
[22]
de Freitas Silva M, Dias KST, Gontijo VS, Ortiz CJC, Viegas C. Jr Multi-Target Directed Drugs as a Modern Approach for Drug Design Towards Alzheimer’s Disease: An Update. Curr Med Chem 2018; 25(29): 3491-525.
[http://dx.doi.org/10.2174/0929867325666180111101843] [PMID: 29332563]
[23]
Gontijo VS, Viegas FPD, Ortiz CJC, et al. Molecular hybridization as a tool in the design of multi-target directed drug candidates for neurodegenerative diseases. Curr Neuropharmacol 2020; 18(5): 348-407.
[http://dx.doi.org/10.2174/1385272823666191021124443] [PMID: 31631821]
[24]
Dias KST, Viegas C. Jr Multi-target directed drugs: A modern approach for design of new drugs for the treatment of Alzheimer’s dis-ease. Curr Neuropharmacol 2014; 12(3): 239-55.
[http://dx.doi.org/10.2174/1570159X1203140511153200] [PMID: 24851088]
[25]
Ray B, Lahiri DK. Neuroinflammation in Alzheimer’s disease: different molecular targets and potential therapeutic agents including curcumin. Curr Opin Pharmacol 2009; 9(4): 434-44.
[http://dx.doi.org/10.1016/j.coph.2009.06.012] [PMID: 19656726]
[26]
Geldenhuys WJ, Van der Schyf CJ. Rationally designed multi-targeted agents against neurodegenerative diseases. Curr Med Chem 2013; 20(13): 1662-72.
[http://dx.doi.org/10.2174/09298673113209990112] [PMID: 23410161]
[27]
Mythri RB, Bharath MM. Curcumin: A potential neuroprotective agent in Parkinson’s disease. Curr Pharm Des 2012; 18(1): 91-9.
[http://dx.doi.org/10.2174/138161212798918995] [PMID: 22211691]
[28]
Harvey AL. Natural products in drug discovery. Drug Discov Today 2008; 13(19-20): 894-901.
[http://dx.doi.org/10.1016/j.drudis.2008.07.004] [PMID: 18691670]
[29]
Campos HC, da Rocha MD, Viegas FPD, et al. The role of natural products in the discovery of new drug candidates for the treatment of neurodegenerative disorders I: Parkinson’s disease. CNS Neurol Disord Drug Targets 2011; 10(2): 239-50.
[http://dx.doi.org/10.2174/187152711794480483] [PMID: 20874702]
[30]
Chen X, Decker M. Multi-target compounds acting in the central nervous system designed from natural products. Curr Med Chem 2013; 20(13): 1673-85.
[http://dx.doi.org/10.2174/0929867311320130007] [PMID: 23410166]
[31]
Amin ARMR, Haque A, Rahman MA, Chen ZG, Khuri FR, Shin DM. Curcumin induces apoptosis of upper aerodigestive tract cancer cells by targeting multiple pathways. PLoS One 2015; 10(4): e0124218.
[http://dx.doi.org/10.1371/journal.pone.0124218] [PMID: 25910231]
[32]
Park W, Amin AR, Chen ZG, Shin DM. New perspectives of curcumin in cancer prevention. Cancer Prev Res (Phila) 2013; 6(5): 387-400.
[http://dx.doi.org/10.1158/1940-6207.CAPR-12-0410] [PMID: 23466484]
[33]
Awasthi M, Upadhyay AK, Singh S, Pandey VP, Dwivedi UN. Terpenoids as promising therapeutic molecules against Alzheimer’s disease: Amyloid beta- and acetylcholinesterase-directed pharmacokinetic and molecular Docking Analyses. Mol Simul 2018; 44(1): 1-11.
[http://dx.doi.org/10.1080/08927022.2017.1334880]
[34]
Yin W, Li Y. Curcumin Upregulate Expression of HO-1 and Nrf-2 in SHSY5Y Cells. 4th International Conference on Bioinformat-ics and Biomedical Engineering, IEEE2010. 1-4.
[http://dx.doi.org/10.1109/ICBBE.2010.5516462]
[35]
Akinyemi AJ, Oboh G, Fadaka AO, Olatunji BP, Akomolafe S. Curcumin administration suppress acetylcholinesterase gene ex-pression in cadmium treated rats. Neurotoxicology 2017; 62: 75-9.
[http://dx.doi.org/10.1016/j.neuro.2017.05.004] [PMID: 28527659]
[36]
Strimpakos AS, Sharma RA. Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal 2008; 10(3): 511-45.
[http://dx.doi.org/10.1089/ars.2007.1769] [PMID: 18370854]
[37]
Wu J, Cai Z, Wei X, et al. Anti-lung cancer activity of the curcumin analog JZ534 in vitro. BioMed Res Int 2015; 2015: 504529.
[http://dx.doi.org/10.1155/2015/504529] [PMID: 25977922]
[38]
Baum L, Ng A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimers Dis 2004; 6(4): 367-77.
[http://dx.doi.org/10.3233/JAD-2004-6403] [PMID: 15345806]
[39]
Dias KST, de Paula CT, Dos Santos T, et al. Jr Design, synthesis and evaluation of novel feruloyl-donepezil hybrids as potential multitarget drugs for the treatment of Alzheimer’s disease. Eur J Med Chem 2017; 130: 440-57.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.043] [PMID: 28282613]
[40]
de Freitas Silva M, Pruccoli L, Morroni F, et al. The Keap1/Nrf2-ARE pathway as a pharmaco-logical target for chalcones. Molecules 2018; 23(7): 1-22.
[http://dx.doi.org/10.3390/molecules23071803] [PMID: 30037040]
[41]
Monroy A, Lithgow GJ, Alavez S. Curcumin and neurodegenerative diseases. Biofactors 2013; 39(1): 122-32.
[http://dx.doi.org/10.1002/biof.1063] [PMID: 23303664]
[42]
Chen Y, Liu X, Jiang C, et al. Curcumin supplementation increases survival and lifespan in Dro-sophila under heat stress conditions. Biofactors 2018; 44(6): 577-87.
[http://dx.doi.org/10.1002/biof.1454] [PMID: 30488487]
[43]
Yu Y, Shen Q, Lai Y, et al. Anti-inflammatory effects of curcumin in microglial cells. Front Pharmacol 2018; 9(APR): 386.
[http://dx.doi.org/10.3389/fphar.2018.00386] [PMID: 29731715]
[44]
Orteca G, Tavanti F, Bednarikova Z, et al. Curcumin derivatives and Aβ-fibrillar aggregates: An interactions’ study for diagnostic/therapeutic purposes in neuro-degenerative diseases. Bioorg Med Chem 2018; 26(14): 4288-300.
[http://dx.doi.org/10.1016/j.bmc.2018.07.027] [PMID: 30031653]
[45]
Hoppe JB, Coradini K, Frozza RL, et al. Free and nanoencapsulated curcumin suppress β-amyloid-induced cognitive impairments in rats: involvement of BDNF and Akt/GSK-3β signaling pathway. Neurobiol Learn Mem 2013; 106: 134-44.
[http://dx.doi.org/10.1016/j.nlm.2013.08.001] [PMID: 23954730]
[46]
Sang Q, Liu X, Wang L, et al. Curcumin protects an SH-SY5Y cell model of Parkinson’s disease against toxic injury by regulating HSP90. Cell Physiol Biochem 2018; 51(2): 681-91.
[http://dx.doi.org/10.1159/000495326] [PMID: 30463061]
[47]
Oliveri V. Toward the discovery and development of effective modulators of α-synuclein amyloid aggregation. Eur. J. Med. Chem. Else-vier Masson SAS 2019; (April): 10-36.
[48]
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm 2007; 4(6): 807-18.
[http://dx.doi.org/10.1021/mp700113r] [PMID: 17999464]
[49]
Li J, Lee IW, Shin GH, Chen X, Park HJ. Curcumin-Eudragit® E PO solid dispersion: A simple and potent method to solve the problems of curcumin. Eur J Pharm Biopharm 2015; 94: 322-32.
[http://dx.doi.org/10.1016/j.ejpb.2015.06.002] [PMID: 26073546]
[50]
Li J, Shin GH, Chen X, Park HJ. Modified curcumin with hyaluronic acid: Combination of pro-drug and nano-micelle strategy to address the curcumin challenge. Food Res Int 2015; 69: 202-8.
[http://dx.doi.org/10.1016/j.foodres.2014.12.045]
[51]
Ireson CR, Jones DJL, Orr S, et al. Metabo-lism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev 2002; 11(1): 105-11.
[PMID: 11815407]
[52]
Xu Q, Zong L, Chen X, et al. Resvera-trol in the treatment of pancreatic cancer. Ann N Y Acad Sci 2015; 1348(1): 10-9.
[http://dx.doi.org/10.1111/nyas.12837] [PMID: 26284849]
[53]
Zheng Y, Qiang X, Xu R, et al. Design, synthesis and evaluation of pterostilbene β-amino alcohol derivatives as multifunctional agents for Alzheimer’s disease treatment. Bioorg Chem 2018; 78: 298-306.
[http://dx.doi.org/10.1016/j.bioorg.2018.03.016] [PMID: 29625269]
[54]
Jardim FR, de Rossi FT, Nascimento MX, et al. Resveratrol and brain mitochondria: A review Mol Neurobiol. Humana Press Inc. 2018; pp. 2085-101.
[55]
Cao H, Pan X, Li C, Zhou C, Deng F, Li T. Density functional theory calculations for resveratrol. Bioorg Med Chem Lett 2003; 13(11): 1869-71.
[http://dx.doi.org/10.1016/S0960-894X(03)00283-X] [PMID: 12749887]
[56]
Cai YJ, Fang JG, Ma LP, Yang L, Liu ZL. Inhibition of free radical-induced peroxidation of rat liver microsomes by resveratrol and its analogues. Biochim Biophys Acta 2003; 1637(1): 31-8.
[http://dx.doi.org/10.1016/S0925-4439(02)00174-6] [PMID: 12527404]
[57]
Matsuoka A, Takeshita K, Furuta A, Ozaki M, Fukuhara K, Miyata N. The 4′-hydroxy group is responsible for the in vitro cytoge-netic activity of resveratrol. Mutat Res 2002; 521(1-2): 29-35.
[http://dx.doi.org/10.1016/S1383-5718(02)00211-5] [PMID: 12438001]
[58]
Ohguchi K, Tanaka T, Kido T, et al. Effects of hydroxystilbene derivatives on tyrosinase activity. Biochem Biophys Res Commun 2003; 307(4): 861-3.
[http://dx.doi.org/10.1016/S0006-291X(03)01284-1] [PMID: 12878190]
[59]
Rege SD, Geetha T, Griffin GD, Broderick TL, Babu JR. Neuroprotective effects of resveratrol in Alzheimer disease pathology. Front Aging Neurosci 2014; 6(AUG): 218.
[http://dx.doi.org/10.3389/fnagi.2014.00218] [PMID: 25309423]
[60]
Bastianetto S, Ménard C, Quirion R. Neuroprotective action of resveratrol. Biochim Biophys Acta 2015; 1852(6): 1195-201.
[61]
Belguendouz L, Fremont L, Hard A. Resveratrol inhibits metal ion-dependent and independent peroxidation of porcine low-density lipoproteins. Biochem Pharmacol 1997; 53(9): 1347-55.
[62]
Nam Han Y, Yong Ryu S, Hoon Han B. Antioxidant activity of resveratroi closely correlates with its monoamine oxidase-A inhibitory activity. Arch Pharmacol Res 1990; 13(2): 1-4.
[63]
Sánchez-Melgar A, Albasanz JL, Guixà-González R, Saleh N, Selent J, Martín M. The antioxidant resveratrol acts as a non-selective adenosine receptor agonist. Free Radic Biol Med 2019; 135: 261-73.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.03.019] [PMID: 30898665]
[64]
Lamport DJ, Pal D, Moutsiana C, et al. The effect of flavanol-rich cocoa on cere-bral perfusion in healthy older adults during conscious resting state: A placebo controlled, crossover, acute trial. Psychopharmacology (Berl) 2015; 232(17): 3227-34.
[http://dx.doi.org/10.1007/s00213-015-3972-4] [PMID: 26047963]
[65]
Miquel S, Champ C, Day J, et al. Poor cognitive ageing: Vulnerabilities, mechanisms and the impact of nutritional interventions. Ageing Res Rev 2018; 42(42): 40-55.
[http://dx.doi.org/10.1016/j.arr.2017.12.004] [PMID: 29248758]
[66]
Calabrese EJ, Calabrese V, Giordano J. Demonstrated hormetic mechanisms putatively subserve riluzole-induced effects in neuropro-tection against amyotrophic lateral sclerosis (ALS): Implications for research and clinical practice. Ageing Res Rev 2021; 67(February): 101273.
[http://dx.doi.org/10.1016/j.arr.2021.101273] [PMID: 33571705]
[67]
Moosavi F, Hosseini R, Saso L, Firuzi O. Modulation of neurotrophic signaling pathways by polyphenols Drug Design, Development and Therapy. Dove Medical Press Ltd. 2015.
[68]
Zhang F, Wang Y Y, Liu H, et al. Resveratrol produces neurotrophic effects on cultured dopaminergic neurons through prompting astroglial BDNF and GDNF release. Evidence-based Complement Altern Med 2012; 2012
[69]
Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides. J Biol Chem 2005; 280(45): 37377-82.
[http://dx.doi.org/10.1074/jbc.M508246200] [PMID: 16162502]
[70]
Liu Q, Zhu D, Jiang P, et al. Resveratrol synergizes with low doses of L-DOPA to improve MPTP-induced Parkinson disease in mice. Behav Brain Res 2019; 367: 10-8.
[http://dx.doi.org/10.1016/j.bbr.2019.03.043] [PMID: 30922940]
[71]
Bellina F, Guazzelli N, Lessi M, Manzini C. Imidazole analogues of resveratrol: synthesis and cancer cell growth evaluation. Tetrahedron 2015; 71(15): 2298-305.
[http://dx.doi.org/10.1016/j.tet.2015.02.024]
[72]
Neves AR, Lucio M, Lima JL, Reis S. Resveratrol in medicinal chemistry: A critical review of its pharmacokinetics, drug-delivery, and membrane interactions. Curr Med Chem 2012; 19(11): 1663-81.
[http://dx.doi.org/10.2174/092986712799945085] [PMID: 22257059]
[73]
Hua T, Vemuri K, Pu M, et al. Crystal structure of the human cannabinoid receptor CB1. Cell 2016; 167(3): 750-762.e14.
[http://dx.doi.org/10.1016/j.cell.2016.10.004] [PMID: 27768894]
[74]
Maccarrone M. Missing pieces to the endocannabinoid puzzle. Trends Mol Med 2019; 1-10.
[PMID: 31822395]
[75]
Han Q-W, Yuan Y-H, Chen N-H. The therapeutic role of cannabinoid receptors and its agonists or antagonists in Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry 2020; 96(96): 109745.
[http://dx.doi.org/10.1016/j.pnpbp.2019.109745] [PMID: 31442553]
[76]
Pisanti S, Malfitano AM, Ciaglia E, et al. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol Ther 2017; 175: 133-50.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.041] [PMID: 28232276]
[77]
Bloomfield MAP, Hindocha C, Green SF, et al. The neuropsychopharmacology of cannabis: A review of human imaging studies. Pharmacol Ther 2019; 195: 132-61.
[http://dx.doi.org/10.1016/j.pharmthera.2018.10.006] [PMID: 30347211]
[78]
Benito C. Tolón, R.M.; Castillo, A.I.; Ruiz-Valdepeñas, L.; Martínez-Orgado, J.A.; Fernández-Sánchez, F.J.; Vázquez, C.; Cravatt, B.F.; Romero, J. β-Amyloid exacerbates inflammation in astrocytes lacking fatty acid amide hydrolase through a mechanism involving PPAR-α PPAR-γ and TRPV1, but not CB or CB receptors. Br J Pharmacol 2012; 166(4): 1474-89.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01889.x] [PMID: 22321194]
[79]
Luis J, Costa GP, Maia LO, Villares JC, Fernandez MA. Neurobiology of cannabis: From the endocannabinoid system to canna-bis-related disorder. J Bras Psiquiatr 2011; 60(11): 111-22.
[80]
Hofmann ME, Frazier CJ. Marijuana, endocannabinoids, and epilepsy: potential and challenges for improved therapeutic intervention. Exp Neurol 2013; 244: 43-50.
[http://dx.doi.org/10.1016/j.expneurol.2011.11.047] [PMID: 22178327]
[81]
Pamplona FA. What are cannabis-based medicines used For? Rev da Biol 2014; 13(1): 28-35.
[http://dx.doi.org/10.7594/revbio.13.01.05]
[82]
Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 2003; 42(4): 327-60.
[http://dx.doi.org/10.2165/00003088-200342040-00003] [PMID: 12648025]
[83]
Bedse G, Romano A, Cianci S, et al. Altered expression of the CB1 cannabinoid receptor in the triple transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis 2014; 40(3): 701-12.
[http://dx.doi.org/10.3233/JAD-131910] [PMID: 24496074]
[84]
Battista N, Di Tommaso M, Bari M, Maccarrone M. The endocannabinoid system: An overview. Front Behav Neurosci 2012; 6(6): 9.
[PMID: 22457644]
[85]
Paloczi J, Varga ZV, Hasko G, Pacher P. Neuroprotection in oxidative stress-related neurodegenerative diseases: Role of endocanna-binoid system modulation. Antioxid Redox Signal 2018; 29(1): 75-108.
[http://dx.doi.org/10.1089/ars.2017.7144] [PMID: 28497982]
[86]
Patil KR, Goyal SN, Sharma C, Patil CR, Ojha S. Phytocannabinoids for cancer therapeutics: Recent updates and future prospects. Curr Med Chem 2015; 22(30): 3472-501.
[http://dx.doi.org/10.2174/0929867322666150716115057] [PMID: 26179998]
[87]
Campos AC, Fogaça MV, Sonego AB, Guimarães FS. Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacol Res 2016; 112: 119-27.
[http://dx.doi.org/10.1016/j.phrs.2016.01.033] [PMID: 26845349]
[88]
Long LE, Malone DT, Taylor DA. The pharmacological actions of cannabidiol. Drugs Future 2005; 747-53.
[http://dx.doi.org/10.1358/dof.2005.030.07.915908]
[89]
Zuardi AW, Crippa JAS, Hallak JEC, Moreira FA, Guimarães FS. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res 2006; 39(4): 421-9.
[http://dx.doi.org/10.1590/S0100-879X2006000400001] [PMID: 16612464]
[90]
Cilio MR, Thiele EA, Devinsky O. The case for assessing cannabidiol in epilepsy. Epilepsia 2014; 55(6): 787-90.
[http://dx.doi.org/10.1111/epi.12635] [PMID: 24854434]
[91]
Campos AC, Fogaça MV, Scarante FF, et al. Plastic and neuroprotective mechanisms involved in the therapeutic effects of cannabidiol in psychiatric disorders. Front Pharmacol 2017; 8(MAY): 269.
[http://dx.doi.org/10.3389/fphar.2017.00269] [PMID: 28588483]
[92]
Burstein S. Cannabidiol (CBD) and its analogs: A review of their effects on inflammation. Bioorg Med Chem 2015; 23(7): 1377-85.
[http://dx.doi.org/10.1016/j.bmc.2015.01.059] [PMID: 25703248]
[93]
Laprairie RB, Bagher AM, Kelly MEM, Denovan-Wright EM. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol 2015; 172(20): 4790-805.
[http://dx.doi.org/10.1111/bph.13250] [PMID: 26218440]
[94]
Ye L, Cao Z, Wang W, Zhou N. New insights in cannabinoid receptor structure and signaling. Curr Mol Pharmacol 2019; 12(3): 239-48.
[http://dx.doi.org/10.2174/1874467212666190215112036] [PMID: 30767756]
[95]
Scherma M, Masia P, Deidda M, Fratta W, Tanda G, Fadda P. New perspectives on the use of cannabis in the treatment of psychiat-ric disorders. Medicines (Basel) 2018; 5(4): 107.
[http://dx.doi.org/10.3390/medicines5040107] [PMID: 30279403]
[96]
Fernández-Ruiz J, Sagredo O, Pazos MR, et al. Cannabidiol for neurodegenera-tive disorders: important new clinical applications for this phytocannabinoid? Br J Clin Pharmacol 2013; 75(2): 323-33.
[http://dx.doi.org/10.1111/j.1365-2125.2012.04341.x] [PMID: 22625422]
[97]
Rosenthaler S, Pöhn B, Kolmanz C, et al. Differences in recep-tor binding affinity of several phytocannabinoids do not explain their effects on neural cell cultures. Neurotoxicol Teratol 2014; 46: 49-56.
[http://dx.doi.org/10.1016/j.ntt.2014.09.003] [PMID: 25311884]
[98]
Pellati F, Borgonetti V, Brighenti V, Biagi M, Benvenuti S, Corsi L. Cannabis sativa L. and nonpsychoactive cannabinoids: their chemistry and role against oxidative stress, inflammation, and cancer. BioMed Res Int 2018; 2018: 1691428.
[http://dx.doi.org/10.1155/2018/1691428] [PMID: 30627539]
[99]
Pernoncini KV. Usos Terapêuticos Potenciais Do Canabidiol Obtido Da Cannabis Sativa. Rev. UNINGÁ Rev 2014; 20(3): 101-6.
[100]
Karl T, Garner B, Cheng D. The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease. Behav Pharmacol 2017; 28(2-3 Special Issue): 142-160.
[http://dx.doi.org/10.1097/FBP.0000000000000247]
[101]
Zuardi AW, Crippa JAS, Hallak JEC. Cannabis sativa: The plant that can produce undesirable effects and also treat them. Rev Bras Psiquiatr 2010; 32(Suppl. 1): 6-7.
[http://dx.doi.org/10.1590/S1516-44462010000500001]
[102]
Martínez-Pinilla E, Varani K, Reyes-Resina I, et al. Binding and signaling studies disclose a potential allosteric site for cannabidiol in canna-binoid CB2 Receptors. Front Pharmacol 2017; 8(OCT): 744.
[http://dx.doi.org/10.3389/fphar.2017.00744] [PMID: 29109685]
[103]
Hill AJ, Williams CM, Whalley BJ, Stephens GJ. Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther 2012; 133(1): 79-97.
[http://dx.doi.org/10.1016/j.pharmthera.2011.09.002] [PMID: 21924288]
[104]
Russo EB. Cannabidiol Claims and Misconceptions. Trends Pharmacol Sci 2017; 38(3): 198-201.
[http://dx.doi.org/10.1016/j.tips.2016.12.004] [PMID: 28089139]
[105]
Cordeiro Pedrazzi JF, De Castro Issy Pereira AC, Gomes FV, Del Bel E. Perfil antipsicótico do canabidiol. Med 2014; 47(2): 112-9.
[106]
Grotenhermen F. Pharmacology of cannabinoids. Neuroendocrinol Lett 2004; 25(1-2): 14-23.
[PMID: 15159677]
[107]
Di Marzo V. New approaches and challenges to targeting the endocannabinoid system. Nat Rev Drug Discov 2018; 17(9): 623-39.
[http://dx.doi.org/10.1038/nrd.2018.115] [PMID: 30116049]
[108]
Muller C, Morales P, Reggio PH. Cannabinoid ligands targeting TRP channels. Front Mol Neurosci 2019; 11: 487.
[http://dx.doi.org/10.3389/fnmol.2018.00487] [PMID: 30697147]
[109]
Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS. Multiple mechanisms involved in the large-spectrum therapeu-tic potential of cannabidiol in psychiatric disorders. Philos Trans R Soc Lond B Biol Sci 2012; 367(1607): 3364-78.
[http://dx.doi.org/10.1098/rstb.2011.0389] [PMID: 23108553]
[110]
Szaflarski JP, Bebin EM. Cannabis, cannabidiol, and epilepsy--from receptors to clinical response. Epilepsy Behav 2014; 41: 277-82.
[http://dx.doi.org/10.1016/j.yebeh.2014.08.135] [PMID: 25282526]
[111]
Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential thera-peutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 2014; 55(6): 791-802.
[http://dx.doi.org/10.1111/epi.12631] [PMID: 24854329]
[112]
Fonseca BM, Costa MA, Almada M, Soares A, Correia-da-Silva G, Teixeira NA. O Sistema endocanabinóide – uma perspetiva terapêutica the endocannabinoid system - a therapeutic perspective. Acta Farm Port 2013; 2(2): 97-104.
[113]
Deiana S. Medical use of cannabis. Cannabidiol: A new light for schizophrenia? Drug Test Anal 2013; 5(1): 46-51.
[http://dx.doi.org/10.1002/dta.1425] [PMID: 23109356]
[114]
Sartim AG, Moreira FA, Joca SRL. Involvement of CB1 and TRPV1 receptors located in the ventral medial prefrontal cortex in the modulation of stress coping behavior. Neuroscience 2017; 340: 126-34.
[http://dx.doi.org/10.1016/j.neuroscience.2016.10.031] [PMID: 27771531]
[115]
Sales AJ, Crestani CC, Guimarães FS, Joca SRL. Antidepressant-like effect induced by Cannabidiol is dependent on brain seroto-nin levels. Prog Neuropsychopharmacol Biol Psychiatry 2018; 86(June): 255-61.
[http://dx.doi.org/10.1016/j.pnpbp.2018.06.002] [PMID: 29885468]
[116]
Cassano T, Villani R, Pace L, et al. From Cannabis sativa to Cannabidiol: Promising therapeutic candidate for the treatment of neurodegenerative diseases. Front Pharmacol 2020; 11(March): 124.
[http://dx.doi.org/10.3389/fphar.2020.00124] [PMID: 32210795]
[117]
Rosenberg EC, Tsien RW, Whalley BJ, Devinsky O. Cannabinoids and epilepsy. Neurotherapeutics 2015; 12(4): 747-68.
[http://dx.doi.org/10.1007/s13311-015-0375-5] [PMID: 26282273]
[118]
Leo A, Russo E, Elia M. Cannabidiol and epilepsy: Rationale and therapeutic potential. Pharmacol Res 2016; 107: 85-92.
[http://dx.doi.org/10.1016/j.phrs.2016.03.005] [PMID: 26976797]
[119]
Zuardi AW. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev Bras Psiquiatr 2008; 30(3): 271-80.
[http://dx.doi.org/10.1590/S1516-44462008000300015] [PMID: 18833429]
[120]
Sales AJ, Fogaça MV, Sartim AG, et al. Cannabidiol induces rapid and sustained antidepressant-like effects through increased BDNF signaling and synaptogenesis in the prefrontal cortex. Mol Neurobiol 2018; 1-12.
[PMID: 29869197]
[121]
Lohar V, Rathore AS. Cannabinoids: Pharmacological profile of promising molecules. Phytopharmacology 2013; 4(1): 41-52.
[122]
Jones NA, Glyn SE, Akiyama S, et al. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure 2012; 21(5): 344-52.
[http://dx.doi.org/10.1016/j.seizure.2012.03.001] [PMID: 22520455]
[123]
Renard J, Loureiro M, Rosen LG, et al. Cannabidiol counteracts amphetamine-induced neuronal and behavioral sensitization of the mesolimbic dopamine pathway through a novel mTOR/p70S6 kinase signaling pathway. J Neurosci 2016; 36(18): 5160-9.
[http://dx.doi.org/10.1523/JNEUROSCI.3387-15.2016] [PMID: 27147666]
[124]
Iovino L, Tremblay ME, Civiero L. Glutamate-induced excitotoxicity in Parkinson’s disease: The role of glial cells. J Pharmacol Sci 2020; 144(3): 151-64.
[http://dx.doi.org/10.1016/j.jphs.2020.07.011] [PMID: 32807662]
[125]
Abe K, Abe Y, Saito H. Agmatine suppresses nitric oxide production in microglia. Brain Res 2000; 872(1-2): 141-8.
[http://dx.doi.org/10.1016/S0006-8993(00)02517-8] [PMID: 10924686]
[126]
Akaishi T, Abe K. CNB-001, a synthetic pyrazole derivative of curcumin, suppresses lipopolysaccharide-induced nitric oxide produc-tion through the inhibition of NF-κB and p38 MAPK pathways in microglia. Eur J Pharmacol 2018; 819(819): 190-7.
[http://dx.doi.org/10.1016/j.ejphar.2017.12.008] [PMID: 29221948]
[127]
Bisceglia F, Seghetti F, Serra M, et al. Prenylated curcumin analogues as multipotent tools to tackle Alzheimer’s disease. ACS Chem Neurosci 2019; 10(3): 1420-33.
[http://dx.doi.org/10.1021/acschemneuro.8b00463] [PMID: 30556996]
[128]
Bolognesi ML, Bartolini M, Tarozzi A, et al. Multitargeted drugs discovery: balancing anti-amyloid and anticholinesterase capacity in a single chemical entity. Bioorg Med Chem Lett 2011; 21(9): 2655-8.
[http://dx.doi.org/10.1016/j.bmcl.2010.12.093] [PMID: 21236667]
[129]
Bolognesi ML, Bartolini M, Tarozzi A, et al. Multitargeted drugs discovery: Balancing anti-amyloid and anticholinesterase capacity in a single chemical entity Bioorg Med Chem Lett. Pergamon 2011; Vol. 21: pp. 2655-8.
[http://dx.doi.org/10.1016/j.bmcl.2010.12.093]
[130]
Bekdash RA. The cholinergic system, the adrenergic system and the neuropathology of Alzheimer’s disease. Int J Mol Sci 2021; 1-18.
[131]
Chojnacki JE, Liu K, Saathoff JM, Zhang S. Bivalent ligands incorporating curcumin and diosgenin as multifunctional compounds against Alzheimer’s disease. Bioorg Med Chem 2015; 23(22): 7324-31.
[http://dx.doi.org/10.1016/j.bmc.2015.10.032] [PMID: 26526742]
[132]
Chojnacki JE, Liu K, Yan X, et al. Discovery of 5-(4-hydroxyphenyl)-3-oxo-pentanoic acid [2-(5-methoxy-1H-indol-3-yl)-ethyl]-amide as a neuroprotectant for Alzheimer’s disease by hybridization of curcumin and melatonin. ACS Chem Neurosci 2014; 5(8): 690-9.
[http://dx.doi.org/10.1021/cn500081s] [PMID: 24825313]
[133]
Di Martino RMC, De Simone A, Andrisano V, et al. Versatility of the curcumin scaffold: Discovery of potent and balanced dual BACE-1 and GSK-3β inhibitors. J Med Chem 2016; 59(2): 531-44.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00894] [PMID: 26696252]
[134]
Elmegeed GA, Ahmed HH, Hashash MA, Abd-Elhalim MM, El-kady DS. Synthesis of novel steroidal curcumin derivatives as anti-Alzheimer’s disease candidates: Evidences-based on in vivo study. Steroids 2015; 101: 78-89.
[http://dx.doi.org/10.1016/j.steroids.2015.06.003] [PMID: 26079653]
[135]
Harish G, Venkateshappa C, Mythri RB, et al. Bioconjugates of curcumin display improved protection against glutathione depletion mediated oxidative stress in a dopaminergic neuronal cell line: Implications for Parkinson’s disease. Bioorg Med Chem 2010; 18(7): 2631-8.
[http://dx.doi.org/10.1016/j.bmc.2010.02.029] [PMID: 20227282]
[136]
Shi Q, Zhang Q, Peng Y, Zhang X, Wang Y, Shi L. A natural diarylheptanoid protects cortical neurons against oxygen-glucose dep-rivation-induced autophagy and apoptosis. J Pharm Pharmacol 2019; 71(7): 1110-8.
[http://dx.doi.org/10.1111/jphp.13096] [PMID: 31025371]
[137]
Simoni E, Bergamini C, Fato R, et al. Polyamine conjugation of curcumin analogues toward the discovery of mitochondria-directed neuroprotective agents. J Med Chem 2010; 53(19): 7264-8.
[http://dx.doi.org/10.1021/jm100637k] [PMID: 20831222]
[138]
Xu J, Zhou L, Weng Q, Xiao L, Li Q. Curcumin analogues attenuate Aβ 25-35 -induced oxidative stress in PC12 cells via Keap1/Nrf2/HO-1 signaling pathways. Chem Biol Interact 2018; 2019(305): 171-9.
[139]
Sang Z, Pan W, Wang K, et al. Design, synthesis and evaluation of novel ferulic acid-O-alkylamine derivatives as potential multifunctional agents for the treatment of Alzheimer’s disease. Eur J Med Chem 2017; 130: 379-92.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.039] [PMID: 28279845]
[140]
Xiao G, Li Y, Qiang X, et al. Design, synthesis and biological eval-uation of 4′-aminochalcone-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer’s disease. Bioorg Med Chem 2017; 25(3): 1030-41.
[http://dx.doi.org/10.1016/j.bmc.2016.12.013] [PMID: 28011206]
[141]
Wan Y, Liang Y, Liang F, et al. A curcumin analog reduces levels of the Alzheimer’s disease-associated amyloid-β protein by modulating AβPP processing and autophagy. J Alzheimers Dis 2019; 72(3): 761-71.
[http://dx.doi.org/10.3233/JAD-190562] [PMID: 31640096]
[142]
Shrikanth Gadad B, K. Subramanya. P.; Pullabhatla, S.; S. Shantharam, I.; K.S, R. Curcumin-Glucoside, A novel synthetic derivative of curcumin, inhibits synuclein oligomer formation: relevance to Parkinson’s disease. Curr Pharm Des 2012; 18(1): 76-84.
[http://dx.doi.org/10.2174/138161212798919093] [PMID: 22211690]
[143]
Liao L, Shi J, Jiang C, et al. Activation of anti-oxidant of curcumin pyrazole derivatives through preservation of mitochondria function and Nrf2 signaling pathway. Neurochem Int 2019; 125(February): 82-90.
[http://dx.doi.org/10.1016/j.neuint.2019.01.026] [PMID: 30771374]
[144]
Li Y, Peng P, Tang L, Hu Y, Hu Y, Sheng R. Design, synthesis and evaluation of rivastigmine and curcumin hybrids as site-activated multitarget-directed ligands for Alzheimer’s disease therapy. Bioorg Med Chem 2014; 22(17): 4717-25.
[http://dx.doi.org/10.1016/j.bmc.2014.07.009] [PMID: 25082512]
[145]
Jirásek P, Amslinger S, Heilmann J. Synthesis of natural and non-natural curcuminoids and their neuroprotective activity against gluta-mate-induced oxidative stress in HT-22 cells. J Nat Prod 2014; 77(10): 2206-17.
[http://dx.doi.org/10.1021/np500396y] [PMID: 25313922]
[146]
Lee SY, Chiu YJ, Yang SM, et al. Novel synthetic chalcone-coumarin hybrid for Aβ aggregation reduction, antioxidation, and neuroprotection. CNS Neurosci Ther 2018; 24(12): 1286-98.
[http://dx.doi.org/10.1111/cns.13058] [PMID: 30596401]
[147]
He XX, Yang XH, Ou RY, et al. Synthesis and evaluation of multifunctional feru-lic and caffeic acid dimers for Alzheimer’s disease. Nat Prod Res 2017; 31(6): 734-7.
[http://dx.doi.org/10.1080/14786419.2016.1219862] [PMID: 27531418]
[148]
Liu K, Gandhi R, Chen J, Zhang S. Bivalent ligands targeting multiple pathological factors involved in Alzheimer’s disease. ACS Med Chem Lett 2012; 3(11): 942-6.
[http://dx.doi.org/10.1021/ml300229y] [PMID: 23293731]
[149]
Liu Z, Fang L, Zhang H, Gou S, Chen L. Design, synthesis and biological evaluation of multifunctional tacrine-curcumin hybrids as new cholinesterase inhibitors with metal ions-chelating and neuroprotective property. Bioorg Med Chem 2017; 25(8): 2387-98.
[http://dx.doi.org/10.1016/j.bmc.2017.02.049] [PMID: 28302511]
[150]
Pan W, Hu K, Bai P, et al. Design, synthesis and evaluation of novel ferulic acid-memoquin hybrids as potential multifunctional agents for the treatment of Alzheimer’s disease. Bioorg Med Chem Lett 2016; 26(10): 2539-43.
[http://dx.doi.org/10.1016/j.bmcl.2016.03.086] [PMID: 27072909]
[151]
Pandareesh MD, Shrivash MK, Naveen Kumar HN, Misra K, Srinivas Bharath MM. Curcumin monoglucoside shows improved bioavailability and mitigates rotenone induced neurotoxicity in cell and drosophila models of Parkinson’s disease. Neurochem Res 2016; 41(11): 3113-28.
[http://dx.doi.org/10.1007/s11064-016-2034-6] [PMID: 27535828]
[152]
Qneibi M, Hamed O, Natsheh AR, et al. Inhibition and assess-ment of the biophysical gating properties of GluA2 and GluA2/A3 AMPA receptors using curcumin derivatives. PLoS One 2019; 14(8): e0221132.
[http://dx.doi.org/10.1371/journal.pone.0221132] [PMID: 31454362]
[153]
Lo Cascio F, Puangmalai N, Ellsworth A, et al. Toxic tau oligomers modulated by novel curcumin derivatives. Sci Rep 2019; 9(1): 19011.
[http://dx.doi.org/10.1038/s41598-019-55419-w] [PMID: 31831807]
[154]
Xia CL, Wang N, Guo QL, et al. Design, synthesis and evaluation of 2-arylethenyl-N-methylquinolinium derivatives as effective multifunctional agents for Alzheimer’s disease treatment. Eur J Med Chem 2017; 130: 139-53.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.042] [PMID: 28242549]
[155]
Yang HL, Cai P, Liu QH, et al. Design, synthesis, and evaluation of salicyladimine derivatives as multitarget-directed ligands against Alzheimer’s disease. Bioorg Med Chem 2017; 25(21): 5917-28.
[http://dx.doi.org/10.1016/j.bmc.2017.08.048] [PMID: 28988627]
[156]
Xu P, Zhang M, Sheng R, Ma Y. Synthesis and biological evaluation of deferiprone-resveratrol hybrids as antioxidants, Aβ1-42 aggre-gation inhibitors and metal-chelating agents for Alzheimer’s disease. Eur J Med Chem 2017; 127: 174-86.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.045] [PMID: 28061347]
[157]
Tacrine-Resveratrol Fused Hybrids as Multi-Target-Directed Ligands against Alzheimer’s Disease.Pdf. 2011.
[158]
Deshmukh P, Unni S, Krishnappa G, Padmanabhan B. The Keap1-Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases. Biophys Rev 2017; 9(1): 41-56.
[http://dx.doi.org/10.1007/s12551-016-0244-4] [PMID: 28510041]
[159]
Deck LM, Whalen LJ, Hunsaker LA, Royer RE, Vander Jagt DL. Activation of anti-oxidant Nrf2 signaling by substituted trans stilbenes. Bioorg Med Chem 2017; 25(4): 1423-30.
[http://dx.doi.org/10.1016/j.bmc.2017.01.005] [PMID: 28126440]
[160]
Martínez A, Alcendor R, Rahman T, Podgorny M, Sanogo I, Mccurdy R. Bioorganic & medicinal chemistry ionophoric polyphenols selectively bind Cu2+, display potent antioxidant and antiamyloidogenic properties, and are non-toxic toward tetrahymena thermophila. 2016; 24: 3657-3670.
[161]
Martínez A, Zahran M, Gomez M, et al. Novel multi-target compounds in the quest for new chemotherapies against Alzheimer’s disease: An experimental and theoretical study. Bioorg Med Chem 2018; 26(17): 4823-40.
[http://dx.doi.org/10.1016/j.bmc.2018.08.019] [PMID: 30181028]
[162]
Cheng G, Xu P, Zhang M, Chen J, Sheng R, Ma Y. Resveratrol-maltol hybrids as multi-target-directed agents for Alzheimer’s dis-ease. Bioorg Med Chem 2018; 26(22): 5759-65.
[http://dx.doi.org/10.1016/j.bmc.2018.08.011] [PMID: 30360953]
[163]
Lan JS, Liu Y, Hou JW, et al. Design, synthesis and evaluation of resvera-trol-indazole hybrids as novel monoamine oxidases inhibitors with amyloid-β aggregation inhibition. Bioorg Chem 2018; 76: 130-9.
[http://dx.doi.org/10.1016/j.bioorg.2017.11.009] [PMID: 29172101]
[164]
Tang YW, Shi CJ, Yang HL, et al. Synthesis and evaluation of isoprenylation-resveratrol dimer derivatives against Alzheimer’s disease. Eur J Med Chem 2019; 163: 307-19.
[http://dx.doi.org/10.1016/j.ejmech.2018.11.040] [PMID: 30529634]
[165]
Tang L, Li M-H, Cao P, et al. Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives. J Biol Chem 2005; 280(35): 31220-9.
[http://dx.doi.org/10.1074/jbc.M500805200] [PMID: 15985434]
[166]
Li W, Yang X, Song Q, et al. Pyridoxine-resveratrol hybrids as novel inhibitors of MAO-B with anti-oxidant and neuroprotective activities for the treatment of Parkinson’s disease. Bioorg Chem 2020; 97(97): 103707.
[http://dx.doi.org/10.1016/j.bioorg.2020.103707] [PMID: 32146176]
[167]
Fukuhara K, Nakanishi I, Kansui H, et al. Enhanced radical-scavenging activity of a planar catechin analogue. J Am Chem Soc 2002; 124(21): 5952-3.
[http://dx.doi.org/10.1021/ja0178259] [PMID: 12022823]
[168]
Fukuhara K, Nakanishi I, Matsuoka A, et al. Effect of methyl substitution on the antioxidative property and genotoxicity of resveratrol. Chem Res Toxicol 2008; 21(2): 282-7.
[http://dx.doi.org/10.1021/tx7003008] [PMID: 18177016]
[169]
Imai K, Nakanishi I, Ohno A, et al. Synthesis and radical-scavenging activity of a dimethyl catechin analogue. Bioorg Med Chem Lett 2014; 24(11): 2582-4.
[http://dx.doi.org/10.1016/j.bmcl.2014.03.029] [PMID: 24792463]
[170]
Li S, Wang X, Kong L. Synthesis and biological evaluation of imine resveratrol derivatives as multi-targeted agents against Alzheimer’s disease. Eur J Med Chem 2014; 71: 36-45.
[171]
Jiang N, Li S, Xie S, et al. Synthesis and evaluation of multifunctional salphen derivatives for the treatment of Alzheimer’s disease. Eur J Med Chem 2014; 87: 540-51.
[172]
Chao J, Li H, Cheng KW, Yu MS, Chang RCC, Wang M. Protective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. J Nutr Biochem 2010; 21(6): 482-9.
[http://dx.doi.org/10.1016/j.jnutbio.2009.02.004] [PMID: 19443200]
[173]
De Santi C, Pietrabissa A, Spisni R, Mosca F, Pacifici GM. Sulphation of resveratrol, a natural compound present in wine, and its inhibition by natural flavonoids. Xenobiotica 2000; 30(9): 857-66.
[http://dx.doi.org/10.1080/004982500433282] [PMID: 11055264]
[174]
de Santi C, Pietrabissa A, Mosca F, Pacifici GM. Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver. Xenobiotica 2000; 30(11): 1047-54.
[http://dx.doi.org/10.1080/00498250010002487] [PMID: 11197066]
[175]
De Santi C, Pietrabissa A, Spisni R, Mosca F, Pacifici GM. Sulphation of resveratrol, a natural product present in grapes and wine, in the human liver and duodenum. Xenobiotica 2000; 30(6): 609-17.
[http://dx.doi.org/10.1080/004982500406435] [PMID: 10923862]
[176]
Hoshino J, Park EJ, Kondratyuk TP, et al. Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites. J Med Chem 2010; 53(13): 5033-43.
[http://dx.doi.org/10.1021/jm100274c] [PMID: 20527891]
[177]
Breuer A, Haj CG, Fogaça MV, et al. Fluorinated cannabidiol derivatives: Enhancement of activity in mice models predictive of anxiolytic, an-tidepressant and antipsychotic effects. PLoS One 2016; 11(8): 1-19.
[http://dx.doi.org/10.1371/journal.pone.0158779]
[178]
Perez M, Cartarozzi LP, Chiarotto GB, Oliveira SA, Guimarães FS, Oliveira ALR. Neuronal preservation and reactive gliosis attenuation following neonatal sciatic nerve axotomy by a fluorinated cannabidiol derivative. Neuropharmacology 2018; 140(April): 201-8.
[http://dx.doi.org/10.1016/j.neuropharm.2018.08.009] [PMID: 30096328]
[179]
Kinney WA, McDonnell ME, Zhong HM, et al. Discovery of KLS-13019, a cannabidiol-derived neuroprotective agent, with improved potency, safety, and permeability. ACS Med Chem Lett 2016; 7(4): 424-8.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00009] [PMID: 27096053]
[180]
Brenneman DE, Petkanas D, Kinney WA. Pharmacological comparisons between cannabidiol and KLS-13019. J Mol Neurosci 2018; 66(1): 121-34.
[http://dx.doi.org/10.1007/s12031-018-1154-7] [PMID: 30109468]
[181]
Brenneman DE, Kinney WA, Ward SJ. Knockdown siRNA targeting the mitochondrial sodium-calcium exchanger-1 inhibits the pro-tective effects of two cannabinoids against acute paclitaxel toxicity. J Mol Neurosci 2019; 68(4): 603-19.
[http://dx.doi.org/10.1007/s12031-019-01321-z] [PMID: 31077084]
[182]
Kozela E, Juknat A, Kaushansky N, Rimmerman N, Ben-Nun A, Vogel Z. Cannabinoids decrease the th17 inflammatory autoim-mune phenotype. J Neuroimmune Pharmacol 2013; 8(5): 1265-76.
[http://dx.doi.org/10.1007/s11481-013-9493-1] [PMID: 23892791]
[183]
Kozela E, Lev N, Kaushansky N, et al. Cannabidiol inhibits patho-genic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice. Br J Pharmacol 2011; 163(7): 1507-19.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01379.x] [PMID: 21449980]
[184]
Kozela E, Juknat A, Gao F, Kaushansky N, Coppola G, Vogel Z. Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells. J Neuroinflammation 2016; 13(1): 136.
[http://dx.doi.org/10.1186/s12974-016-0603-x] [PMID: 27256343]
[185]
Juknat A, Kozela E, Kaushansky N, Mechoulam R, Vogel Z. Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol - studies in BV-2 microglia and encephalitogenic T cells. J Basic Clin Physiol Pharmacol 2016; 27(3): 289-96.
[http://dx.doi.org/10.1515/jbcpp-2015-0071] [PMID: 26540221]
[186]
Bolton JL, Trush MA, Penning TM, Dryhurst G, Monks TJ. Role of quinones in toxicology. Chem Res Toxicol 2000; 13(3): 135-60.
[http://dx.doi.org/10.1021/tx9902082] [PMID: 10725110]
[187]
Kogan NM, Rabinowitz R, Levi P, et al. Synthesis and antitumor activity of qui-nonoid derivatives of cannabinoids. J Med Chem 2004; 47(15): 3800-6.
[http://dx.doi.org/10.1021/jm040042o] [PMID: 15239658]
[188]
Appendino G, Bellido Cabello de Alba M L, Blanco E M WO. 2015/158381 Al, 2015.
[189]
Del Rio C, Cantarero I, Palomares B, et al. VCE-004.3, a cannabidiol aminoquinone de-rivative, prevents bleomycin-induced skin fibrosis and inflammation through PPARγ- and CB2 receptor-dependent pathways. Br J Pharmacol 2018; 175(19): 3813-31.
[http://dx.doi.org/10.1111/bph.14450] [PMID: 30033591]
[190]
Navarrete C, Carrillo-Salinas F, Palomares B, et al. Hypoxia mimetic activity of VCE-004.8, a cannabidiol quinone derivative: implications for multiple sclerosis therapy. J Neuroinflammation 2018; 15(1): 64.
[http://dx.doi.org/10.1186/s12974-018-1103-y] [PMID: 29495967]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy