Abstract
Background: Alzheimer’s disease (AD) is one of the most prevalent types of dementia, affecting millions of older people worldwide. AD is stimulating efforts to develop novel molecules targeting its main features associated with a decrease in acetylcholine levels, an increase in oxidative stress and depositions of amyloid-β (Aβ) and tau protein. In this regard, selenium-containing compounds have been demonstrated as potential multi-targeted compounds in the treatment of AD. These compounds are known for their antioxidant and anticholinesterase properties, causing a decrease in Aβ aggregation.
Objective: In this review, we approach structure-activity relationships of each compound, associating the decrease of ROS activity, an increase of tau-like activity and inhibition of AChE with a decrease in the self-aggregation of Aβ.
Methods: We also verify that the molecular descriptors apol, nHBAcc and MlogP may be related to optimized pharmacokinetic properties for anti-AD drugs.
Results: In our analysis, few selenium-derived compounds presented similar molecular features to FDA-approved drugs.
Conclusion: We suggest that unknown selenium-derived molecules with apol, nHBAcc and MlogP like FDA-approved drugs may be better successes with optimized pharmacokinetic properties in future studies in AD.
Keywords: Organoselenium, Alzheimer’s disease, multi-targeted drugs, antioxidant, GPx, Selenium.
[http://dx.doi.org/10.1177/1179573520907397] [PMID: 32165850]
[http://dx.doi.org/10.1038/s41583-019-0240-3] [PMID: 31780819]
[http://dx.doi.org/10.1186/s12877-019-1175-2] [PMID: 31266451]
[http://dx.doi.org/10.3389/fphar.2019.01109] [PMID: 31611794]
[http://dx.doi.org/10.1186/s12877-020-1417-3] [PMID: 32005158]
[http://dx.doi.org/10.1016/j.tins.2018.06.002] [PMID: 30053949]
[http://dx.doi.org/10.1016/S0006-291X(84)80190-4] [PMID: 6375662]
[http://dx.doi.org/10.1073/pnas.82.12.4245] [PMID: 3159021]
[http://dx.doi.org/10.1126/science.2949367] [PMID: 2949367]
[http://dx.doi.org/10.1038/325733a0] [PMID: 2881207]
[http://dx.doi.org/10.2174/1567205012666151020114607] [PMID: 26651341]
[http://dx.doi.org/10.1016/S0925-4439(00)00043-0] [PMID: 10899442]
[http://dx.doi.org/10.1177/0891988710383571] [PMID: 21045163]
[http://dx.doi.org/10.1093/hmg/9.3.325] [PMID: 10655540]
[http://dx.doi.org/10.2217/fnl.14.35] [PMID: 26146489]
[http://dx.doi.org/10.1084/jem.20150892] [PMID: 26481686]
[http://dx.doi.org/10.1038/nm0896-864] [PMID: 8705854]
[http://dx.doi.org/10.1016/j.nbd.2004.04.018] [PMID: 15474359]
[http://dx.doi.org/10.1111/jnc.12202] [PMID: 23406382]
[http://dx.doi.org/10.1038/nrdp.2015.56] [PMID: 27188934]
[http://dx.doi.org/10.1146/annurev-neuro-061010-113613] [PMID: 21456963]
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.12.024] [PMID: 18304698]
[http://dx.doi.org/10.1126/science.1197623] [PMID: 21148344]
[http://dx.doi.org/10.1038/s41386-019-0478-5] [PMID: 31408876]
[http://dx.doi.org/10.1212/WNL.42.3.631] [PMID: 1549228]
[http://dx.doi.org/10.1001/archneur.1995.00540250089017] [PMID: 7826280]
[http://dx.doi.org/10.1001/archneur.60.5.729] [PMID: 12756137]
[http://dx.doi.org/10.1016/j.biopha.2018.06.147] [PMID: 29990843]
[http://dx.doi.org/10.1186/s13195-021-00838-z] [PMID: 33971962]
[PMID: 16649847]
[http://dx.doi.org/10.1016/S0891-5849(01)00724-9] [PMID: 11728801]
[http://dx.doi.org/10.1155/2019/2105607] [PMID: 31210837]
[http://dx.doi.org/10.1016/0304-3835(80)90021-X] [PMID: 6772298]
[http://dx.doi.org/10.1080/01635588609513890] [PMID: 3737421]
[http://dx.doi.org/10.1039/D0OB00629G] [PMID: 32353091]
[http://dx.doi.org/10.1158/1940-6207.CAPR-08-0173] [PMID: 19401524]
[http://dx.doi.org/10.1016/S0304-3835(00)00585-1] [PMID: 11053649]
[http://dx.doi.org/10.1046/j.1464-410x.1998.00630.x] [PMID: 9634050]
[http://dx.doi.org/10.2174/2212796811307010003]
[http://dx.doi.org/10.1021/cr0406559] [PMID: 15584701]
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]
[http://dx.doi.org/10.1021/ci025584y] [PMID: 12653513]
[http://dx.doi.org/10.2174/138161206777585274] [PMID: 16796559]
[http://dx.doi.org/10.1186/1758-2946-6-3] [PMID: 24479757]
[http://dx.doi.org/10.1186/s13321-017-0220-4] [PMID: 29086040]
[http://dx.doi.org/10.1021/js980402t] [PMID: 10430548]
[http://dx.doi.org/10.1080/10916460500214992]
[http://dx.doi.org/10.1021/cn500119g] [PMID: 25121395]
[http://dx.doi.org/10.1155/2015/976908] [PMID: 26090073]
[http://dx.doi.org/10.1016/j.bmc.2017.11.019] [PMID: 29157728]
[http://dx.doi.org/10.2174/1570179416666190719112423] [PMID: 31984888]
[http://dx.doi.org/10.1016/j.tetlet.2017.07.039]
[http://dx.doi.org/10.1016/j.biopha.2018.06.049] [PMID: 30021335]
[http://dx.doi.org/10.1007/s11904-018-0386-z]
[http://dx.doi.org/10.1016/j.cbi.2018.08.004] [PMID: 30120923]
[http://dx.doi.org/10.1080/14756366.2016.1210139] [PMID: 28133981]
[http://dx.doi.org/10.1016/j.ejmech.2017.06.048] [PMID: 28728108]
[http://dx.doi.org/10.1002/mnfr.201800107] [PMID: 29688618]
[http://dx.doi.org/10.1016/j.redox.2018.09.014] [PMID: 30308475]
[http://dx.doi.org/10.1016/j.neuroscience.2014.07.068] [PMID: 25130558]
[http://dx.doi.org/10.1016/j.tetlet.2017.08.030]
[http://dx.doi.org/10.1016/j.jnutbio.2012.06.012] [PMID: 22959057]
[http://dx.doi.org/10.1016/j.neulet.2010.01.057] [PMID: 20122991]
[http://dx.doi.org/10.1016/j.bbr.2013.03.034] [PMID: 23557695]
[http://dx.doi.org/10.1002/cbf.1741] [PMID: 21465495]
[http://dx.doi.org/10.1016/j.expneurol.2011.11.036] [PMID: 22173317]
[http://dx.doi.org/10.1007/s12035-018-0939-6] [PMID: 29430618]
[http://dx.doi.org/10.1016/j.neuropharm.2011.10.007] [PMID: 22032870]
[http://dx.doi.org/10.1016/0891-5849(93)90028-S] [PMID: 8458589]
[http://dx.doi.org/10.1016/0306-3623(95)00003-J] [PMID: 7590103]
[http://dx.doi.org/10.1177/0748233713509429] [PMID: 24231787]
[http://dx.doi.org/10.1007/s00775-017-1463-2] [PMID: 28502066]
[http://dx.doi.org/10.1002/jcb.26731] [PMID: 29405440]
[http://dx.doi.org/10.1016/j.jpsychires.2018.11.021] [PMID: 30521994]
[http://dx.doi.org/10.1016/j.bmc.2016.08.017] [PMID: 27567080]
[http://dx.doi.org/10.1039/C5RA26797H]
[http://dx.doi.org/10.1039/C5DT02130H] [PMID: 26575390]
[http://dx.doi.org/10.1016/j.bmc.2018.10.022] [PMID: 30385227]
[http://dx.doi.org/10.1039/C4OB00598H] [PMID: 24752799]