{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T07:16:49Z","timestamp":1771658209822,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T00:00:00Z","timestamp":1543276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21502025"],"award-info":[{"award-number":["21502025"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Science Foundation for the Doctoral Program of Guangdong Medical University","award":["B2017011"],"award-info":[{"award-number":["B2017011"]}]},{"name":"the Students' Innovative Program of Guangdong Province","award":["201810571096"],"award-info":[{"award-number":["201810571096"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex and multifactorial neurodegenerative disorder of aged people. The development of multitarget-directed ligands (MTDLs) to act as multifunctional agents to treat this disease is the mainstream of current research. As a continuation of our previous studies, a series of 4-flexible amino-2-arylethenylquinoline derivatives as multi-target agents was efficiently synthesized and evaluated for the treatment of AD. Among these synthesized derivatives, some compounds exhibited strong self-induced A\u03b21\u201342 aggregation inhibition and antioxidant activity. The structure-activity relationship was summarized, which confirmed that the introduction of a flexible amino group featuring a N,N-dimethylaminoalkylamino moiety at the 4-position increased the A\u03b21\u201342 aggregation inhibition activity, with an inhibition ratio of 95.3% at 20 \u03bcM concentration. Compound 6b1, the optimal compound, was able to selectively chelate copper (II), and inhibit Cu2+-induced A\u03b2 aggregation effectively. It also could disassemble the self-induced A\u03b21\u201342 aggregation fibrils with a ratio of 64.3% at 20 \u03bcM concentration. Moreover, compound 6b1 showed low toxicity and a good neuroprotective effect against A\u03b21\u201342-induced toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test indicated compound 6b1 significantly reversed scopolamine-induced memory deficit in mice. Taken together, these results suggested that compound 6b1 was a promising multi-target compound worthy of further study for AD.<\/jats:p>","DOI":"10.3390\/molecules23123100","type":"journal-article","created":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T12:17:35Z","timestamp":1543321055000},"page":"3100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Preparation of 4-Flexible Amino-2-Arylethenyl-Quinoline Derivatives as Multi-Target Agents for the Treatment of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Xiao-Qin","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Guangdong Medical University, Dongguan 523808, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chu-Ping","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Medical University, Dongguan 523808, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long-Cheng","family":"Zhong","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Medical University, Dongguan 523808, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De-Ling","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Medical University, Dongguan 523808, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De-Hao","family":"Mai","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Medical University, Dongguan 523808, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Gui","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Medical University, Dongguan 523808, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Hua","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Medical University, Dongguan 523808, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13195-016-0207-9","article-title":"Drug development in Alzheimer\u2019s disease: The path to 2025","volume":"8","author":"Cummings","year":"2016","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1126\/science.1132814","article-title":"A century of Alzheimer\u2019s disease","volume":"314","author":"Goedert","year":"2006","journal-title":"Science"},{"key":"ref_3","unstructured":"Prince, M., Wimo, A., Guerchet, M., Ail, G.C., Wu, Y.T., and Prina, M. (2015). World Alzheimer Report 2015. The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost and Trends, The Alzheimer\u2019s Disease International."},{"key":"ref_4","unstructured":"(2018, January 15). Dementia Statistics, Alzheimer\u2019s Disease International. Available online: http:\/\/www.alz.co.uk\/research\/statistics."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/alzrt269","article-title":"Alzheimer\u2019s disease drug-development pipeline: Few candidates, frequent failures","volume":"6","author":"Cummings","year":"2014","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.nbd.2017.03.014","article-title":"A\u03b2 propagation and strains: Implications for the phenotypic diversity in Alzheimer\u2019s disease","volume":"109","author":"Condello","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S1474-4422(03)00502-7","article-title":"Treatment of Alzheimer\u2019s disease: Current status and new perspectives","volume":"2","author":"Scarpini","year":"2003","journal-title":"Lancet Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5193","DOI":"10.1021\/cr300009x","article-title":"Bioinorganic chemistry of Alzheimer\u2019s disease","volume":"112","author":"Kepp","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1021\/jm3015926","article-title":"Target and mechanism-based therapeutics for neurodegenerative diseases: Strength in numbers","volume":"56","author":"Trippier","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1021\/ar500152x","article-title":"The ongoing search for small molecules to study metal-associated amyloid-\u03b2 species in Alzheimer\u2019s disease","volume":"47","author":"Savelieff","year":"2014","journal-title":"Acc. Chem. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fphar.2015.00221","article-title":"\u03b2-Amyloid: The key peptide in the pathogenesis of Alzheimer\u2019s disease","volume":"6","author":"Sun","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1523\/JNEUROSCI.2381-04.2005","article-title":"Nucleation-dependent polymerization is an essential component of amyloid-mediated neuronal cell death","volume":"25","author":"Wogulis","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.ejmech.2016.12.009","article-title":"Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-\u03b2-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer\u2019s disease","volume":"126","author":"Li","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease: Progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1515\/revneuro-2017-0063","article-title":"Amyloid toxicity in Alzheimer\u2019s disease","volume":"29","author":"Reiss","year":"2018","journal-title":"Rev. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1126\/science.1091230","article-title":"ABAD directly links A\u03b2 to mitochondrial toxicity in Alzheimer\u2019s disease","volume":"304","author":"Lustbader","year":"2004","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/jemt.1121","article-title":"Microglial interaction with \u03b2-amyloid: Implications for the pathogenesis of Alzheimer\u2019s disease","volume":"54","author":"Bamberger","year":"2001","journal-title":"Microsc Res. Tech."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3410","DOI":"10.1073\/pnas.0507313103","article-title":"AMPA receptor downscaling at the onset of Alzheimer\u2019s disease pathology in double knockin mice","volume":"10","author":"Chang","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6625","DOI":"10.1021\/ja210588m","article-title":"Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the A\u03b242 Peptide","volume":"134","author":"Sharma","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11915","DOI":"10.1038\/ncomms11915","article-title":"Early synaptic deficits in the APP\/PS1 mouse model of Alzheimer\u2019s disease involve neuronal adenosine A2A receptors","volume":"7","author":"Haberl","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jchemneu.2011.05.014","article-title":"Neuropsin\u2014A possible modulator of synaptic plasticity","volume":"42","author":"Shiosaka","year":"2011","journal-title":"J. Chem. Neuroanat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.neuroscience.2015.02.034","article-title":"Lysophosphatidylcholine increases the neurotoxicity of Alzheimer\u2019s amyloid \u03b21\u201342 peptide: Role of oligomer formation","volume":"292","author":"Sheikh","year":"2015","journal-title":"Neuroscience"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1007\/s11064-015-1730-y","article-title":"Rhynchophylline Protects Against the Amyloid \u03b2-Induced Increase of Spontaneous Discharges in the Hippocampal CA1 Region of Rats","volume":"40","author":"Shao","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.neurobiolaging.2009.04.016","article-title":"Advanced glycation endproducts and their receptor RAGE in Alzheimer\u2019s disease","volume":"32","author":"Srikanth","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/aps.2011.14","article-title":"Small molecule inhibitors of amyloid \u03b2 peptide aggregation as a potential therapeutic strategy for Alzheimer\u2019s disease","volume":"32","author":"Nie","year":"2011","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"86","DOI":"10.2174\/156720509787602861","article-title":"Cholinesterase inhibitors and beyond","volume":"6","author":"Pepeu","year":"2009","journal-title":"Curr. Alzheimer Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rana, M., and Sharma, A.K. (2018). Cu and Zn interactions with A\u03b2 peptides: Consequence of coordination on aggregation and formation of neurotoxic soluble A\u03b2 oligomers. Metallomics, in press.","DOI":"10.1039\/C8MT00203G"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1089\/ars.2012.5027","article-title":"Amyloid \u03b2-Peptide(1\u201342)-Induced Oxidative Stress in Alzheimer Disease: Importance in Disease Pathogenesis and Progression","volume":"19","author":"Butterfield","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.nbd.2015.08.007","article-title":"The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer\u2019s disease: Two sides of the same coin","volume":"81","author":"Peters","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"223","DOI":"10.3233\/JAD-2008-15208","article-title":"Drug development based on the metals hypothesis of Alzheimer\u2019s Disease","volume":"15","author":"Bush","year":"2008","journal-title":"J. Alzheimers. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2217\/bmm-2017-0456","article-title":"Oxidative stress as a biomarker for Alzheimer\u2019s disease","volume":"12","author":"Collin","year":"2018","journal-title":"Biomark. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/187152708783885156","article-title":"Alzheimer Disease and the Role of Free Radicals in the Pathogenesis of the Disease","volume":"7","author":"Perry","year":"2008","journal-title":"CNS. Neurol. Disord. Drug Targets"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1038\/nm0908-894","article-title":"Hope in Alzheimer\u2019s fight emerges from unexpected places","volume":"14","author":"Gura","year":"2008","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/gps.1402","article-title":"A systematic review of the clinical effectiveness of donepezil, rivastigmine and galantamine on cognition, quality of life and adverse events in Alzheimer\u2019s disease","volume":"21","author":"Takeda","year":"2006","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.2174\/1568026616666160927160620","article-title":"Hybrid Compounds as Direct Multitarget Ligands: A Review","volume":"17","author":"Ishiki","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/med.20248","article-title":"Recent advances in the multitarget-directed ligands approach for the treatment of Alzheimer\u2019s disease","volume":"33","author":"Leon","year":"2013","journal-title":"Med. Res. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.2174\/1568026616666160927154116","article-title":"Novel Multitarget Hybrid Compounds for the Treatment of Alzheimer\u2019s Disease","volume":"17","author":"Michalska","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.ejmech.2014.10.018","article-title":"Design, synthesis, and biological evaluation of 2-arylethenylquinoline derivatives as multifunctional agents for the treatment of Alzheimer\u2019s disease","volume":"89","author":"Wang","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_41","unstructured":"Wang, X.Q. (2014). Synthesis and Evaluation of 2-arylethenylquinoline Derivatives as Potential Agents for the Treatment of Alzheimer\u2019s Disease. [Ph.D. Thesis, Sun Yat-sen University]. (In Chinese)."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.3987\/COM-16-13516","article-title":"Microwave-Assisted Efficient Synthesis of 4-Substituted Amino-2-methyl-quinolines Catalyzed by p-Toluenesulfonic Acid","volume":"92","author":"Wang","year":"2016","journal-title":"Heterocycles"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Panek, D., Wi\u0119ckowska, A., Pasieka, A., Gody\u0144, J., Jo\u0144czyk, J., Bajda, M., Knez, D., Gobec, S., and Malawska, B. (2018). Design, Synthesis, and Biological Evaluation of 2-(Benzylamino-2-Hydroxyalkyl)Isoindoline-1,3-Diones Derivatives as Potential Disease-Modifying Multifunctional Anti-Alzheimer Agents. Molecules, 23.","DOI":"10.3390\/molecules23020347"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1021\/jm050746d","article-title":"Novel tacrine-melatonin hybrids as dual-acting drugs for Alzheimer disease, with improved acetylcholinesterase inhibitory and antioxidant properties","volume":"49","author":"Pearez","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Li, B., Huang, A.L., Zhang, Y.L., Li, Z., Ding, H.W., Huang, C., Meng, X.M., and Li, J. (2017). Design, Synthesis and Evaluation of Hesperetin Derivatives as Potential Multifunctional Anti-Alzheimer Agents. Molecules, 22.","DOI":"10.3390\/molecules22071067"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0006-8993(94)91429-X","article-title":"Characterization of 2\u2032,7\u2032-dichloro-fluorescin fluorescence in dissociated mammalian brain neurons: Estimation on intra cellular content of hydrogen peroxide","volume":"635","author":"Oyama","year":"1994","journal-title":"Brain Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8483","DOI":"10.1021\/jm300978h","article-title":"Multitarget-directed benzylideneindanone derivatives: Anti-\u03b2-amyloid (A\u03b2) aggregation, antioxidant, metal chelation, and monoamine oxidase B (MAO-B) inhibition properties against Alzheimer\u2019s disease","volume":"55","author":"Huang","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4823","DOI":"10.1016\/j.bmc.2018.08.019","article-title":"Novel multi-target compounds in the quest for new chemotherapies against Alzheimer\u2019s disease: An experimental and theoretical study","volume":"26","author":"Zahran","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ejmech.2013.10.068","article-title":"Design, synthesis and biological evaluation of imine resveratrol derivatives as multi-targeted agents against Alzheimer\u2019s disease","volume":"71","author":"Li","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Hussein, W., Sa\u011fl\u0131k, B.N., Levent, S., Korkut, B., Ilg\u0131n, S., \u00d6zkay, Y., and Kaplanc\u0131kl\u0131, Z.A. (2018). Synthesis and Biological Evaluation of New Cholinesterase Inhibitors for Alzheimer\u2019s Disease. Molecules, 23.","DOI":"10.3390\/molecules23082033"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1002\/cmdc.201700456","article-title":"Minor Structural Variations of Small Molecules Tune Regulatory Activities toward Pathological Factors in Alzheimer\u2019s Disease","volume":"12","author":"Beck","year":"2017","journal-title":"ChemMedChem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.ejmech.2014.09.081","article-title":"Discovery of indanone derivatives as multi-target-directed ligands against Alzheimer\u2019s disease","volume":"87","author":"Huang","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Purgatorio, R., de Candia, M., De Palma, A., De Santis, F., Pisani, L., Campagna, F., Cellamare, S., Altomare, C.D., and Catto, M. (2018). Insights into Structure-Activity Relationships of 3-Arylhydrazonoindolin-2-One Derivatives for Their Multitarget Activity on \u03b2-Amyloid Aggregation and Neurotoxicity. Molecules, 23.","DOI":"10.3390\/molecules23071544"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Fu, Y., Mu, Y., Lei, H., Wang, P., Li, X., Leng, Q., Han, L., Qu, X., Wang, Z., and Huang, X. (2016). Design, Synthesis and Evaluation of Novel Tacrine-Ferulic Acid Hybrids as Multifunctional Drug Candidates against Alzheimer\u2019s Disease. Molecules, 21.","DOI":"10.3390\/molecules21101338"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ejmech.2017.02.039","article-title":"Design, synthesis and evaluation of novel ferulic acid-O-alkylamine derivativesas potential multifunctional agents for the treatment of Alzheimer\u2019s disease","volume":"130","author":"Sang","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.ejmech.2017.04.054","article-title":"Design, synthesis and evaluation of scutellarein-O-acetamidoalkyl-benzylamines as potential multifunctional agents for the treatment of Alzheimer\u2019s disease","volume":"135","author":"Sang","year":"2017","journal-title":"Eur. J. Med. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/12\/3100\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:32:39Z","timestamp":1760196759000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/12\/3100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,27]]},"references-count":56,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["molecules23123100"],"URL":"https:\/\/doi.org\/10.3390\/molecules23123100","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,27]]}}}