Curcumin Analogues as Novel Anti-Alzheimer's Candidates: Synthesis Development Strategy, In Vitro, Cell-Based and In Vivo Studies

  • Yance Anas Doctoral Program of Pharmacy Science, Faculty of Pharmacy, University of Gadjah Mada, Yogyakarta, Indonesia, 55281; Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Wahid Hasyim, Semarang, Indonesia, 50236
  • Ratna Asmah Susidarti Department of Pharmacy Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia, 55281
  • Nunung Yuniarti Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia, 55281
  • Ronny Martien Department of Pharmaceutics, Faculty of Pharmacy, Universitas of Gadjah Mada, Yogyakarta, Indonesia, 55281
Keywords: Curcumin analogues, anti-Alzheimer’s candidates, Aβ biosynthesis, cell-based assay, transgenic mice

Abstract

Alzheimer's disease (AD) is a neurological illness that causes a wide range of cognitive symptoms linked to amyloid plaque deposition, neurofibrillary tangles, oxidative stress, and neuron death in the whole brain. Curcumin has shown promising efficacy in preclinical studies for AD treatment. However, it failed to exhibit expected clinical outcomes in clinical studies. Besides, this molecule has low stability, solubility, and bioavailability properties. Hence, scientists have synthesized several curcumin analogues to improve their bioavailability and biological activity. The purpose of this narrative review is to discuss the development of curcumin analogue synthesis published in 2016-2021 and its efficacy that reveals its effect as an anti-Alzheimer's candidate through in vitro, cell-based and in vivo studies. Pubmed and Scopus database search engine with the keywords "curcumin" AND "analogues" OR "analogs" AND "Alzheimer's" were used to find the relevant studies. In our review, we include sixteen eligible journal articles to discuss. Fifteen curcumin analogues exhibited promise efficacy in preclinical studies and are suitable for development as anti-Alzheimer's candidates. Further study should explore to confirm the curcumin analogues toxicity, develop an appropriate dosage form, and initiate clinical trials.

References

Aggarwal, B. B., & Harikumar, K. B. (2009). Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. The International Journal of Biochemistry & Cell Biology, 41(1), 40–59. https://doi.org/10.1016/j.biocel.2008.06.010

Akaishi, T., & Abe, K. (2018). CNB-001, a synthetic pyrazole derivative of curcumin, suppresses lipopolysaccharide-induced nitric oxide production through the inhibition of NF-κB and p38 MAPK pathways in microglia. European Journal of Pharmacology, 819, 190–197. Scopus. https://doi.org/10.1016/j.ejphar.2017.12.008

Andrade, S., Ramalho, M. J., Loureiro, J. A., & Pereira, M. do C. (2019). Natural compounds for Alzheimer’s disease therapy: a systematic review of preclinical and clinical studies. International Journal of Molecular Sciences, 20(9), Article 9. https://doi.org/10.3390/ijms20092313

Atri, A. (2019). The Alzheimer’s disease clinical spectrum: diagnosis and management. Medical Clinics, 103(2), 263–293. https://doi.org/10.1016/j.mcna.2018.10.009

Atwood, C. S., Moir, R. D., Huang, X., Scarpa, R. C., Bacarra, N. M., Romano, D. M., Hartshorn, M. A., Tanzi, R. E., & Bush, A. I. (1998). Dramatic aggregation of Alzheimer abeta by Cu(II) is induced by conditions representing physiological acidosis. The Journal of Biological Chemistry, 273(21), 12817–12826. https://doi.org/10.1074/jbc.273.21.12817

Azzi, E., Alberti, D., Parisotto, S., Oppedisano, A., Protti, N., Altieri, S., Geninatti-Crich, S., & Deagostino, A. (2019). Design, synthesis and preliminary in-vitro studies of novel boronated monocarbonyl analogues of Curcumin (BMAC) for antitumor and β-amiloyd disaggregation activity. Bioorganic Chemistry, 93, 103324. https://doi.org/10.1016/j.bioorg.2019.103324

Ba, F., Pang, P. K. T., & Benishin, C. G. (2003). The establishment of a reliable cytotoxic system with SK-N-SH neuroblastoma cell culture. Journal of Neuroscience Methods, 123(1), 11–22. https://doi.org/10.1016/s0165-0270(02)00324-2

Bachiller, S., Jiménez-Ferrer, I., Paulus, A., Yang, Y., Swanberg, M., Deierborg, T., & Boza-Serrano, A. (2018). Microglia in neurological diseases: a road map to brain-disease dependent-inflammatory response. Frontiers in Cellular Neuroscience, 12. https://www.frontiersin.org/article/10.3389/fncel.2018.00488

Barik, A., Mishra, B., Shen, L., Mohan, H., Kadam, R. M., Dutta, S., Zhang, H.-Y., & Priyadarsini, K. I. (2005). Evaluation of a new copper(II)-curcumin complex as superoxide dismutase mimic and its free radical reactions. Free Radical Biology & Medicine, 39(6), 811–822. https://doi.org/10.1016/j.freeradbiomed.2005.05.005

Barry, A. E., Klyubin, I., Mc Donald, J. M., Mably, A. J., Farrell, M. A., Scott, M., Walsh, D. M., & Rowan, M. J. (2011). Alzheimer’s disease brain-derived amyloid-β-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 31(20), 7259–7263. https://doi.org/10.1523/JNEUROSCI.6500-10.2011

Benameur, T., Giacomucci, G., Panaro, M. A., Ruggiero, M., Trotta, T., Monda, V., Pizzolorusso, I., Lofrumento, D. D., Porro, C., & Messina, G. (2021). New promising therapeutic avenues of curcumin in brain diseases. Molecules (Basel, Switzerland), 27(1), 236. https://doi.org/10.3390/molecules27010236

Benek, O., Korabecny, J., & Soukup, O. (2020). A Perspective on multi-target drugs for alzheimer's disease. Trends in pharmacological sciences, 41(7), 434–445. https://doi.org/10.1016/j.tips.2020.04.008

Bisceglia, F., Seghetti, F., Serra, M., Zusso, M., Gervasoni, S., Verga, L., Vistoli, G., Lanni, C., Catanzaro, M., De Lorenzi, E., & Belluti, F. (2019). Prenylated curcumin analogues as multipotent tools to tackle Alzheimer’s disease. ACS Chemical Neuroscience, 10(3), 1420–1433. Scopus. https://doi.org/10.1021/acschemneuro.8b00463

Briggs, R., Kennelly, S. P., & O'Neill, D. (2016). Drug treatments in Alzheimer's disease. Clinical medicine (London, England), 16(3), 247–253. https://doi.org/10.7861/clinmedicine.16-3-247

Bukhari, S. N., & Jantan, I. (2015). Synthetic curcumin analogs as inhibitors of β -Amyloid peptide aggregation: potential therapeutic and diagnostic agents for Alzheimer's disease. Mini reviews in medicinal chemistry, 15(13), 1110–1121. https://doi.org/10.2174/138955751513150923101841

Caccamo, A., Oddo, S., Sugarman, M., Akbari, Y., & LaFerla, F. (2005). Age- and region-dependent alterations in Abeta-degrading enzymes: Implications for Abeta-induced disorders. Neurobiology of Aging, 26(5), 645–654. https://doi.org/10.1016/j.neurobiolaging.2004.06.013

Cetin, S., Knez, D., Gobec, S., Kos, J. & Pišlar, A. (2022). Cell models for Alzheimer’s and Parkinson’s disease: at the interface of biology and drug discovery. Biomedicine & Pharmacotherapy, 149(2022), 112924 https://doi.org/10.1016/j.biopha.2022.112924

Chainoglou, E., Siskos, A., Pontiki, E., & Hadjipavlou-Litina, D. (2020). Hybridization of curcumin analogues with cinnamic acid derivatives as multi-target agents against Alzheimer’s disease targets. Molecules, 25(21), 4958. https://doi.org/10.3390/molecules25214958

Chakrabarty, P., Hudson, V. J., Sacino, A. N., Brooks, M. M. T., D’Alton, S., Lewis, J., Golde, T. E., & Giasson, B. I. (2015). Inefficient induction and spread of seeded tau pathology in P301L mouse model of tauopathy suggests inherent physiological barriers to transmission. Acta Neuropathologica, 130(2), 303–305. https://doi.org/10.1007/s00401-015-1444-x

Chami, L., Buggia-Prévot, V., Duplan, E., Del Prete, D., Delprete, D., Chami, M., Peyron, J.-F., & Checler, F. (2012). Nuclear factor-κB regulates βAPP and β- and γ-secretases differently at physiological and supraphysiological Aβ concentrations. The Journal of Biological Chemistry, 287(29), 24573–24584. https://doi.org/10.1074/jbc.M111.333054

Chen, C.-H., Zhou, W., Liu, S., Deng, Y., Cai, F., Tone, M., Tone, Y., Tong, Y., & Song, W. (2012). Increased NF-κB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer’s disease. The International Journal of Neuropsychopharmacology, 15(1), 77–90. https://doi.org/10.1017/S1461145711000149

Chen, J., Yin, W., Tu, Y., Wang, S., Yang, X., Chen, Q., Zhang, X., Han, Y., & Pi, R. (2017). L-F001, a novel multifunctional ROCK inhibitor, suppresses neuroinflammation in vitro and in vivo: Involvement of NF-κB inhibition and Nrf2 pathway activation. European Journal of Pharmacology, 806, 1–9. https://doi.org/10.1016/j.ejphar.2017.03.025

Chen, P.-T., Chen, Z.-T., Hou, W.-C., Yu, L.-C., & Chen, R. P.-Y. (2016). Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer’s disease. Scientific Reports, 6, 29760. https://doi.org/10.1038/srep29760

Cook, C., Carlomagno, Y., Gendron, T. F., Dunmore, J., Scheffel, K., Stetler, C., Davis, M., Dickson, D., Jarpe, M., DeTure, M., & Petrucelli, L. (2014). Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance. Human molecular genetics, 23(1), 104–116. https://doi.org/10.1093/hmg/ddt402

Cummings, J., Reiber, C., & Kumar, P. (2018). The price of progress: funding and financing Alzheimer’s disease drug development. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 4, 330–343. https://doi.org/10.1016/j.trci.2018.04.008

Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2020). Alzheimer’s disease drug development pipeline: 2020. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 6(1), e12050. https://doi.org/10.1002/trc2.12050

Dei Cas, M., & Ghidoni, R. (2019). Dietary curcumin: correlation between bioavailability and health potential. Nutrients, 11(9), 2147. https://doi.org/10.3390/nu11092147

Díaz, A., Rojas, K., Espinosa, B., Chávez, R., Zenteno, E., Limón, D., & Guevara, J. (2014). Aminoguanidine treatment ameliorates inflammatory responses and memory impairment induced by amyloid-beta 25–35 injection in rats. Neuropeptides, 48(3), 153–159. https://doi.org/10.1016/j.npep.2014.03.002

Di Meco, A., Curtis, M. E., Lauretti, E., & Praticò, D. (2020). Autophagy dysfunction in Alzheimer's disease: mechanistic insights and new therapeutic opportunities. Biological psychiatry, 87(9), 797–807. https://doi.org/10.1016/j.biopsych.2019.05.008

Donovan, M. H., Yazdani, U., Norris, R. D., Games, D., German, D. C., & Eisch, A. J. (2006). Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer’s disease. Journal of Comparative Neurology, 495(1), 70–83. https://doi.org/10.1002/cne.20840

Drummond, E., & Wisniewski, T. (2017). Alzheimer's disease: experimental models and reality. Acta neuropathologica, 133(2), 155–175. https://doi.org/10.1007/s00401-016-1662-x

Ferrari, E., Benassi, R., Saladini, M., Orteca, G., Gazova, Z., & Siposova, K. (2017). In vitro study on potential pharmacological activity of curcumin analogues and their copper complexes. Chemical Biology & Drug Design, 89(3), 411–419. https://doi.org/10.1111/cbdd.12847

Ferrari, E., Pignedoli, F., Imbriano, C., Marverti, G., Basile, V., Venturi, E., & Saladini, M. (2011). Newly synthesized curcumin derivatives: Crosstalk between chemico-physical properties and biological activity. Journal of Medicinal Chemistry, 54(23), 8066–8077. https://doi.org/10.1021/jm200872q

Fiala, M., Liu, P. T., Espinosa-Jeffrey, A., Rosenthal, M. J., Bernard, G., Ringman, J. M., Sayre, J., Zhang, L., Zaghi, J., Dejbakhsh, S., Chiang, B., Hui, J., Mahanian, M., Baghaee, A., Hong, P., & Cashman, J. (2007). Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer’s disease patients are improved by bisdemethoxycurcumin. Proceedings of the National Academy of Sciences of the United States of America, 104(31), 12849–12854. https://doi.org/10.1073/pnas.0701267104

Francis, P. T. (2005). The interplay of neurotransmitters in Alzheimer’s disease. CNS Spectrums, 10(11 Suppl 18), 6–9. https://doi.org/10.1017/s1092852900014164

Funderburk, S. F., Marcellino, B. K., & Yue, Z. (2010). Cell "self-eating" (autophagy) mechanism in alzheimer's disease. The Mount Sinai journal of medicine, New York, 77(1), 59–68. https://doi.org/10.1002/msj.20161

Gagliardi, S., Franco, V., Sorrentino, S., Zucca, S., Pandini, C., Rota, P., Bernuzzi, S., Costa, A., Sinforiani, E., Pansarasa, O., Cashman, J. R., & Cereda, C. (2018). Curcumin and novel synthetic analogs in cell-based studies of Alzheimer’s disease. Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.01404

Gagliardi, S., Ghirmai, S., Abel, K. J., Lanier, M., Gardai, S. J., Lee, C., & Cashman, J. R. (2012). Evaluation in vitro of synthetic curcumins as agents promoting monocytic gene expression related to β-amyloid clearance. Chemical Research in Toxicology, 25(1), 101–112. https://doi.org/10.1021/tx200246t

GBD 2019 Dementia Forecasting Collaborators. (2022). Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019. The Lancet Public Health, Januari(2022), 1–21. https://doi.org/10.1016/S2468-2667(21)00249-8

Grimm, M. O. W., Mett, J., Stahlmann, C. P., Haupenthal, V. J., Zimmer, V. C., & Hartmann, T. (2013). Neprilysin and Aβ clearance: impact of the APP intracellular domain in NEP regulation and implications in Alzheimer’s disease. Frontiers in Aging Neuroscience, 5, 98. https://doi.org/10.3389/fnagi.2013.00098

Gupta, A. P., Khan, S., Manzoor, M. M., Yadav, A. K., Sharma, G., Anand, R., & Gupta, S. (2017). Chapter 10 - Anticancer curcumin: natural analogues and structure-activity relationship. In Atta-ur-Rahman (Ed.), Studies in Natural Products Chemistry (Vol. 54, pp. 355–401). Elsevier. https://doi.org/10.1016/B978-0-444-63929-5.00010-3

Hamada, H., Nakayama, T., Shimoda, K., Matsuura, N., Hamada, H., Iwaki, T., Kiriake, Y., & Saikawa, T. (2020). Curcumin oligosaccharides (Gluco-oligosaccharides) penetrate the blood-brain barrier in mouse brain: glycoside (polysaccharide) modification approach for brain drug delivery across the blood-brain barrier and tumor drug delivery. Natural Product Communications, 15(11), 1934578X20953653. https://doi.org/10.1177/1934578X20953653

Harry, G. J., & Kraft, A. D. (2008). Neuroinflammation and Microglia: Considerations and approaches for neurotoxicity assessment. Expert Opinion on Drug Metabolism & Toxicology, 4(10), 1265–1277. https://doi.org/10.1517/17425255.4.10.1265

Heger, M., van Golen, R. F., Broekgaarden, M., & Michel, M. C. (2014). The molecular basis for the pharmacokinetics and pharmacodynamics of curcumin and its metabolites in relation to cancer. Pharmacological Reviews, 66(1), 222–307. https://doi.org/10.1124/pr.110.004044

Hellström-Lindahl, E., Ravid, R., & Nordberg, A. (2008). Age-dependent decline of neprilysin in Alzheimer’s disease and normal brain: Inverse correlation with A beta levels. Neurobiology of Aging, 29(2), 210–221. https://doi.org/10.1016/j.neurobiolaging.2006.10.010

Hewlings, S. J., & Kalman, D. S. (2017). Curcumin: a review of its’ effects on human health. Foods, 6(10), 92. https://doi.org/10.3390/foods6100092

Hillen H (2019) The beta amyloid dysfunction (BAD) hypothesis for Alzheimer’s disease. Front. Neurosci. 13:1154. doi: 10.3389/fnins.2019.01154

Istyastono, E. P., Nurrochmad, A., & Yuniarti, N. (2016). Structure-based virtual screening campaigns on curcuminoids as potent ligands for histone deacetylase-2. Orient J Chem, 32(1), 275-82. Available from: http://www.orientjchem.org/?p=14236

Jung, H. A., Min, B.-S., Yokozawa, T., Lee, J.-H., Kim, Y. S., & Choi, J. S. (2009). Anti-Alzheimer and antioxidant activities of coptidis rhizoma alkaloids. Biol Pharm Bull, 32(8), 1433–1438. https://doi.org/10.1248/bpb.32.1433

Kalaycıoğlu, Z., Gazioğlu, I., & Erim, F. B. (2017). Comparison of antioxidant, anticholinesterase, and antidiabetic activities of three curcuminoids isolated from Curcuma longa L. Natural Product Research, 31(24), 2914–2917. https://doi.org/10.1080/14786419.2017.1299727

Karimipour, M., Rahbarghazi, R., Tayefi, H., Shimia, M., Ghanadian, M., Mahmoudi, J., & Bagheri, H. S. (2019). Quercetin promotes learning and memory performance concomitantly with neural stem/progenitor cell proliferation and neurogenesis in the adult rat dentate gyrus. International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience, 74, 18–26. https://doi.org/10.1016/j.ijdevneu.2019.02.005

Khanna, S., Park, H.-A., Sen, C. K., Golakoti, T., Sengupta, K., Venkateswarlu, S., & Roy, S. (2009). Neuroprotective and antiinflammatory properties of a novel demethylated curcuminoid. Antioxidants & Redox Signaling, 11(3), 449–468. https://doi.org/10.1089/ars.2008.2230

Kilgore, M., Miller, C. A., Fass, D. M., Hennig, K. M., Haggarty, S. J., Sweatt, J. D., & Rumbaugh, G. (2010). Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer's disease. Neuropsychopharmacology, 35(4), 870–880. https://doi.org/10.1038/npp.2009.197

Koenig, A. M., Arnold, S. E., & Streim, J. E. (2016). Agitation and irritability in Alzheimer's disease: evidenced-based treatments and the black-box warning. Current psychiatry reports, 18(1), 3. https://doi.org/10.1007/s11920-015-0640-7

Koo, E. H., & Squazzo, S. L. (1994). Evidence that production and release of amyloid beta-protein involves the endocytic pathway. The Journal of Biological Chemistry, 269(26), 17386–17389.

Kotani, R., Urano, Y., Sugimoto, H., & Noguchi, N. (2017). Decrease of amyloid-β levels by curcumin derivative via modulation of amyloid-β protein precursor trafficking. Journal of Alzheimer’s Disease: JAD, 56(2), 529–542. https://doi.org/10.3233/JAD-160794

Kovalevich, J., & Langford, D. (2013). Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology. Methods in Molecular Biology (Clifton, N.J.), 1078, 9–21. https://doi.org/10.1007/978-1-62703-640-5_2

Kumar, B., Singh, V., Shankar, R., Kumar, K., & Rawal, R. K. (2017). Synthetic and medicinal prospective of structurally modified curcumins. Current Topics in Medicinal Chemistry, 17(2), 148–161. https://doi.org/10.2174/1568026616666160605050052

Lazarov, O., & Marr, R. A. (2010). Neurogenesis and Alzheimer’s disease: At the crossroads. Experimental Neurology, 223(2), 267–281. https://doi.org/10.1016/j.expneurol.2009.08.009

Lee, S. J. C., Nam, E., Lee, H. J., Savelieff, M. G., & Lim, M. H. (2017). Towards an understanding of amyloid-β oligomers: Characterization, toxicity mechanisms, and inhibitors. Chemical Society Reviews, 46(2), 310–323. https://doi.org/10.1039/c6cs00731g

Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Paul Murphy, M., Baker, M., Yu, X., Duff, K., Hardy, J., Corral, A., Lin, W. L., Yen, S. H., Dickson, D. W., Davies, P., & Hutton, M. (2000). Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nature Genetics, 25(4), 402–405. https://doi.org/10.1038/78078

Liu, Y., Dargusch, R., Maher, P., & Schubert, D. (2008). A broadly neuroprotective derivative of curcumin. Journal of Neurochemistry, 105(4), 1336–1345. https://doi.org/10.1111/j.1471-4159.2008.05236.x

Maiti, P., & Dunbar, G. L. (2018). Use of curcumin, a natural polyphenol for targeting molecular pathways in treating age-related neurodegenerative diseases. International Journal of Molecular Sciences, 19(6), Article 6. https://doi.org/10.3390/ijms19061637

Malm, T., Koistinaho, J., & Kanninen, K. (2011). Utilization of APPswe/PS1dE9 transgenic mice in research of Alzheimer’s disease: focus on gene therapy and cell-based therapy applications. International Journal of Alzheimer’s Disease, 2011. https://doi.org/10.4061/2011/517160

Mantzavinos, V., & Alexiou, A. (2017). Biomarkers for Alzheimer's disease diagnosis. Current Alzheimer research, 14(11), 1149–1154. https://doi.org/10.2174/1567205014666170203125942

Noureddin, S. A., El-Shishtawy, R. M., & Al-Footy, K. O. (2019). Curcumin analogues and their hybrid molecules as multifunctional drugs. European Journal of Medicinal Chemistry, 182, 111631. https://doi.org/10.1016/j.ejmech.2019.111631

Nyakas, C., Granic, I., Halmy, L. G., Banerjee, P., & Luiten, P. G. M. (2011). The basal forebrain cholinergic system in aging and dementia. Rescuing cholinergic neurons from neurotoxic amyloid-β42 with memantine. Behavioural Brain Research, 221(2), 594–603. https://doi.org/10.1016/j.bbr.2010.05.033

Oblak, A. L., Lin, P. B., Kotredes, K. P., Pandey, R. S., Garceau, D., Williams, H. M., Uyar, A., O’Rourke, R., O’Rourke, S., Ingraham, C., Bednarczyk, D., Belanger, M., Cope, Z. A., Little, G. J., Williams, S.-P. G., Ash, C., Bleckert, A., Ragan, T., Logsdon, B. A., … Lamb, B. T. (2021). Comprehensive evaluation of the 5XFAD mouse model for preclinical testing applications: A MODEL-AD Study. Frontiers in Aging Neuroscience, 13. https://www.frontiersin.org/article/10.3389/fnagi.2021.713726

Okuda, M., Hijikuro, I., Fujita, Y., Teruya, T., Kawakami, H., Takahashi, T., & Sugimoto, H. (2016). Design and synthesis of curcumin derivatives as tau and amyloid β dual aggregation inhibitors. Bioorganic & Medicinal Chemistry Letters, 26(20), 5024–5028. https://doi.org/10.1016/j.bmcl.2016.08.092

Pinkaew, D., Changtam, C., Tocharus, C., Govitrapong, P., Jumnongprakhon, P., Suksamrarn, A., & Tocharus, J. (2016). Association of neuroprotective effect of Di-O-Demethylcurcumin on Aβ25-35-induced neurotoxicity with suppression of NF-κB and activation of Nrf2. Neurotoxicity Research, 29(1), 80–91. https://doi.org/10.1007/s12640-015-9558-4

Prasad, S., DuBourdieu, D., Srivastava, A., Kumar, P., & Lall, R. (2021). Metal–curcumin complexes in therapeutics: an approach to enhance pharmacological effects of curcumin. International Journal of Molecular Sciences, 22(13), 7094. https://doi.org/10.3390/ijms22137094

Prasad, S., Tyagi, A. K., & Aggarwal, B. B. (2014). Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Research and Treatment : Official Journal of Korean Cancer Association, 46(1), 2–18. https://doi.org/10.4143/crt.2014.46.1.2

Priyadarsini, K. I. (2014). The chemistry of curcumin: from extraction to therapeutic agent. Molecules, 19(12), 20091–20112. https://doi.org/10.3390/molecules191220091

Qi, Z., Wu, M., Fu, Y., Huang, T., Wang, T., Sun, Y., Feng, Z., & Li, C. (2017). Palmitic acid curcumin ester facilitates protection of neuroblastoma against oligomeric Aβ40 insult. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 44(2), 618–633. https://doi.org/10.1159/000485117

Rogan, S., & Lippa, C. F. (2002). Alzheimer’s disease and other dementias: A review. American Journal of Alzheimer’s Disease and Other Dementias, 17(1), 11–17. https://doi.org/10.1177/153331750201700106

Selenica, M. L., Benner, L., Housley, S. B., Manchec, B., Lee, D. C., Nash, K. R., Kalin, J., Bergman, J. A., Kozikowski, A., Gordon, M. N., & Morgan, D. (2014). Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition. Alzheimer's research & therapy, 6(1), 12. https://doi.org/10.1186/alzrt241

Sharma K. (2019). Cholinesterase inhibitors as Alzheimer's therapeutics (Review). Molecular medicine reports, 20(2), 1479–1487. https://doi.org/10.3892/mmr.2019.10374

Smith, J. A., Das, A., Ray, S. K., & Banik, N. L. (2012). Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Research Bulletin, 87(1), 10–20. https://doi.org/10.1016/j.brainresbull.2011.10.004

Solari, N., & Hangya, B. (2018). Cholinergic modulation of spatial learning, memory and navigation. The European Journal of Neuroscience, 48(5), 2199–2230. https://doi.org/10.1111/ejn.14089

Song, J.-X., Malampati, S., Zeng, Y., Durairajan, S. S. K., Yang, C.-B., Tong, B. C.-K., Iyaswamy, A., Shang, W.-B., Sreenivasmurthy, S. G., Zhu, Z., Cheung, K.-H., Lu, J.-H., Tang, C., Xu, N., & Li, M. (2020). A small molecule transcription factor EB activator ameliorates beta-amyloid precursor protein and Tau pathology in Alzheimer’s disease models. Aging Cell, 19(2), e13069. https://doi.org/10.1111/acel.13069

Soria Lopez, J. A., González, H. M., & Léger, G. C. (2019). Chapter 13—Alzheimer’s disease. In S. T. Dekosky & S. Asthana (Eds.), Handbook of Clinical Neurology (Vol. 167, pp. 231–255). Elsevier. https://doi.org/10.1016/B978-0-12-804766-8.00013-3

Strother, L., Miles, G. B., Holiday, A. R., Cheng, Y., & Doherty, G. H. (2021). Long-term culture of SH-SY5Y neuroblastoma cells in the absence of neurotrophins: A novel model of neuronal ageing. Journal of Neuroscience Methods, 362, 109301. https://doi.org/10.1016/j.jneumeth.2021.109301

Sung, P.-S., Lin, P.-Y., Liu, C.-H., Su, H.-C., & Tsai, K.-J. (2020). Neuroinflammation and Neurogenesis in Alzheimer’s Disease and Potential Therapeutic Approaches. International Journal of Molecular Sciences, 21(3), E701. https://doi.org/10.3390/ijms21030701

Tampi, R.R., Forester, B.P., & Agronin, M. (2021). Aducanumab: evidence from clinical trial data and controversies. Drugs Contex, 10. https://doi.org/10.7573/dic.2021-7-3

Thies, W., & Bleiler, L. (2013). 2013 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 9(2), 208–245.

Thinakaran, G., & Koo, E. H. (2008). Amyloid precursor protein trafficking, processing, and function. The Journal of Biological Chemistry, 283(44), 29615–29619. https://doi.org/10.1074/jbc.R800019200

Vasic, V., Barth, K., & Schmidt, M. H. H. (2019). Neurodegeneration and neuro-regeneration—Alzheimer’s disease and stem cell therapy. International Journal of Molecular Sciences, 20(17), 4272. https://doi.org/10.3390/ijms20174272

Venkateswarlu, S., Ramachandra, M. S., & Subbaraju, G. V. (2005). Synthesis and biological evaluation of polyhydroxycurcuminoids. Bioorganic & Medicinal Chemistry, 13(23), 6374–6380. https://doi.org/10.1016/j.bmc.2005.06.050

Viola, K. L., & Klein, W. L. (2015). Amyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis. Acta Neuropathologica, 129(2), 183–206. https://doi.org/10.1007/s00401-015-1386-3

Voulgaropoulou, S. D., van Amelsvoort, T. a. M. J., Prickaerts, J., & Vingerhoets, C. (2019). The effect of curcumin on cognition in Alzheimer’s disease and healthy aging: A systematic review of pre-clinical and clinical studies. Brain Research, 1725, 146476. https://doi.org/10.1016/j.brainres.2019.146476

Wan, Y., Liang, Y., Liang, F., Shen, N., Shinozuka, K., Yu, J.-T., Ran, C., Quan, Q., Tanzi, R. E., & Zhang, C. (2019). A Curcumin analog reduces levels of the Alzheimer’s disease-associated Amyloid-β Protein by modulating AβPP processing and autophagy. Journal of Alzheimer’s Disease: JAD, 72(3), 761–771. https://doi.org/10.3233/JAD-190562

Wang, H., Ma, J., Tan, Y., Wang, Z., Sheng, C., Chen, S., & Ding, J. (2010). Amyloid-beta1-42 induces reactive oxygen species-mediated autophagic cell death in U87 and SH-SY5Y cells. Journal of Alzheimer’s Disease: JAD, 21(2), 597–610. https://doi.org/10.3233/JAD-2010-091207

Wang, X., Wang, C., Wang, J., Zhao, S., Zhang, K., Wang, J., Zhang, W., Wu, C., & Yang, J. (2014). Pseudoginsenoside-F11 (PF11) exerts anti-neuroinflammatory effects on LPS-activated microglial cells by inhibiting TLR4-mediated TAK1/IKK/NF-κB, MAPKs and Akt signaling pathways. Neuropharmacology, 79, 642–656. https://doi.org/10.1016/j.neuropharm.2014.01.022

Weller, J., & Budson, A. (2018). Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Research, 7. https://doi.org/10.12688/f1000research.14506.1

Wetzel, R., Chemuru, S., Misra, P., Kodali, R., Mukherjee, S., & Kar, K. (2018). An aggregate weight-normalized Thioflavin-T measurement scale for characterizing polymorphic amyloids and assembly intermediates. Methods in Molecular Biology (Clifton, N.J.), 1777, 121–144. https://doi.org/10.1007/978-1-4939-7811-3_6

Wu, K. M., Zhang, Y. R., Huang, Y. Y., Dong, Q., Tan, L., & Yu, J. T. (2021). The role of the immune system in Alzheimer's disease. Ageing research reviews, 70, 101409. https://doi.org/10.1016/j.arr.2021.101409

Xu, J., Zhou, L., Weng, Q., Xiao, L., & Li, Q. (2019). Curcumin analogues attenuate Aβ 25-35 -induced oxidative stress in PC12 cells via Keap1/Nrf2/HO-1 signaling pathways. Chemico-Biological Interactions, 305, 171–179. Scopus. https://doi.org/10.1016/j.cbi.2019.01.010

Yan, F.-S., Sun, J.-L., Xie, W.-H., Shen, L., & Ji, H.-F. (2018). Neuroprotective effects and mechanisms of curcumin–Cu(II) and –Zn(II) complexes systems and their pharmacological implications. Nutrients, 10(1), 28. https://doi.org/10.3390/nu10010028

Yan, J., Hu, J., Liu, A., He, L., Li, X., & Wei, H. (2017). Design, synthesis, and evaluation of multitarget-directed ligands against Alzheimer’s disease based on the fusion of donepezil and curcumin. Bioorganic & Medicinal Chemistry, 25(12), 2946–2955. https://doi.org/10.1016/j.bmc.2017.02.048

Yan, Y., Chen, Y., Liu, Z., Cai, F., Niu, W., Song, L., Liang, H., Su, Z., Yu, B., & Yan, F. (2021). Brain delivery of curcumin through low-intensity ultrasound-induced blood-brain barrier opening via lipid-PLGA nanobubbles. International Journal of Nanomedicine, 16, 7433–7447. https://doi.org/10.2147/IJN.S327737

Yang, F., Lim, G. P., Begum, A. N., Ubeda, O. J., Simmons, M. R., Ambegaokar, S. S., Chen, P. P., Kayed, R., Glabe, C. G., Frautschy, S. A., & Cole, G. M. (2005). Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. The Journal of Biological Chemistry, 280(7), 5892–5901. https://doi.org/10.1074/jbc.M404751200

Yavarpour-Bali, H., Ghasemi-Kasman, M., & Pirzadeh, M. (2019). Curcumin-loaded nanoparticles: A novel therapeutic strategy in treatment of central nervous system disorders. International Journal of Nanomedicine, 14, 4449–4460. https://doi.org/10.2147/IJN.S208332

Yiannopoulou, K. G., Anastasiou, A. I., Zachariou, V., & Pelidou, S. H. (2019). Reasons for failed trials of Disease-Modifying Treatments for Alzheimer disease and their contribution in recent research. Biomedicines, 7(4), 97. https://doi.org/10.3390/biomedicines7040097

Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007). Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron, 53(3), 337–351. https://doi.org/10.1016/j.neuron.2007.01.010

Yu, J., Ye, J., Liu, X., Han, Y., & Wang, C. (2011). Protective effect of L-carnitine against H(2)O(2)-induced neurotoxicity in neuroblastoma (SH-SY5Y) cells. Neurological Research, 33(7), 708–716. https://doi.org/10.1179/1743132810Y.0000000028

Zhang, L., Liu, C., Wu, J., Tao, J. J., Sui, X. L., Yao, Z. G., Xu, Y. F., Huang, L., Zhu, H., Sheng, S. L., & Qin, C. (2014). Tubastatin A/ACY-1215 improves cognition in Alzheimer's disease transgenic mice. Journal of Alzheimer's disease : JAD, 41(4), 1193–1205. https://doi.org/10.3233/JAD-140066

Zhang, W., Xu, C., Sun, J., Shen, H. M., Wang, J., & Yang, C. (2022). Impairment of the autophagy-lysosomal pathway in Alzheimer's diseases: pathogenic mechanisms and therapeutic potential. Acta pharmaceutica Sinica. B, 12(3), 1019–1040. https://doi.org/10.1016/j.apsb.2022.01.008

Zheng, Q., Zheng, M., Zhang, T., & He, G. (2016). Hippocampal neurogenesis in the APP/PS1/nestin-GFP triple transgenic mouse model of Alzheimer's disease. Neuroscience, 314, 64–74. https://doi.org/10.1016/j.neuroscience.2015.11.054

Zhou, Z., Chan, C. H., Ma, Q., Xu, X., Xiao, Z., & Tan, E.-K. (2011). The roles of amyloid precursor protein (APP) in neurogenesis, implications to pathogenesis and therapy of Alzheimer disease (AD). Cell Adhesion & Migration, 5(4), 280–292. https://doi.org/10.4161/cam.5.4.16986

Published
2022-12-20
How to Cite
Anas, Y., Ratna Asmah Susidarti, Nunung Yuniarti, & Ronny Martien. (2022). Curcumin Analogues as Novel Anti-Alzheimer’s Candidates: Synthesis Development Strategy, In Vitro, Cell-Based and In Vivo Studies. Indonesian Journal of Pharmacy, 33(4), 493-514. https://doi.org/10.22146/ijp.4432
Section
Review Article