dc.creator | Ahuja Casarín, Ana I. | es |
dc.creator | Merino Montiel, Penélope | es |
dc.creator | Vega Báez, José Luis | es |
dc.creator | Montiel Smith, Sara | es |
dc.creator | Fernandes, Miguel X, | es |
dc.creator | Lagunes, Irene | es |
dc.creator | Maya Castilla, Inés | es |
dc.creator | López López, Óscar | es |
dc.creator | Fernández-Bolaños Guzmán, José María | es |
dc.date.accessioned | 2022-04-08T09:57:19Z | |
dc.date.available | 2022-04-08T09:57:19Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Ahuja Casarín, A.I., Merino Montiel, P., Vega Báez, J.L., Montiel Smith, S., Fernandes, M.X., Lagunes, I.,...,Fernández-Bolaños Guzmán, J.M. (2021). Tuning the activity of iminosugars: novel N-alkylated deoxynojirimycin derivatives as strong BuChE inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 36 (1), 138-146. | |
dc.identifier.issn | 1475-6366 | es |
dc.identifier.uri | https://hdl.handle.net/11441/131985 | |
dc.description.abstract | We have designed unprecedented cholinesterase inhibitors based on 1-deoxynojirimycin as potential anti-Alzheimer’s agents. Compounds are comprised of three key structural motifs: the iminosugar, for interaction with cholinesterase catalytic anionic site (CAS); a hydrocarbon tether with variable lengths, and a fragment derived from 2-phenylethanol for promoting interactions with peripheral anionic site (PAS). Title compounds exhibited good selectivity towards BuChE, strongly depending on the substitution pattern and the length of the tether. The lead compounds were found to be strong mixed inhibitors of BuChE (IC50 = 1.8 and 1.9 µM). The presumptive binding mode of the lead compound was analysed using molecular docking simulations, revealing H-bond interactions with the catalytic subsite (His438) and CAS (Trp82 and Glu197) and van der Waals interactions with PAS (Thr284, Pro285, Asn289). They also lacked significant antiproliferative activity against tumour and non-tumour cells at 100 µM, making them promising new agents for tackling Alzheimer’s disease through the cholinergic approach. | es |
dc.description.sponsorship | Dirección General de Investigación de España. CTQ2016-78703-P | es |
dc.description.sponsorship | Junta de Andalucía. FQM134 | es |
dc.description.sponsorship | Fondo Europeo de Desarrollo Regional (FEDER) y Consejo Nacional de Ciencia y Tecnología de México (CONACYT). CB-2015/257465 | es |
dc.description.sponsorship | Ministerio de Ciencia, Innovación y Universidades y Agencia Estatal de Investigación de España y Fondos FEDER de la Unión Europea (MCIU/AEI/FEDER). PGC2018-094503-B-C22 | es |
dc.format | application/pdf | es |
dc.format.extent | 9 p. | es |
dc.language.iso | eng | es |
dc.publisher | Taylor & Francis Open Access | es |
dc.relation.ispartof | Journal of Enzyme Inhibition and Medicinal Chemistry, 36 (1), 138-146. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Iminosugars | es |
dc.subject | 1-DNJ | es |
dc.subject | cholinesterase inhibitors | es |
dc.subject | anti-Alzheimer’s agents | es |
dc.subject | docking simulations | es |
dc.title | Tuning the activity of iminosugars: novel N-alkylated deoxynojirimycin derivatives as strong BuChE inhibitors | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Química orgánica | es |
dc.relation.projectID | CTQ2016-78703-P | es |
dc.relation.projectID | FQM134 | es |
dc.relation.projectID | CB-2015/257465 | es |
dc.relation.projectID | PGC2018-094503-B-C22 | es |
dc.relation.publisherversion | ttps://doi.org/10.1080/14756366.2020.1847101 | es |
dc.identifier.doi | 10.1080/14756366.2020.1847101 | es |
dc.contributor.group | Universidad de Sevilla. FQM134: Química Fina de Carbohidratos | es |
dc.journaltitle | Journal of Enzyme Inhibition and Medicinal Chemistry | es |
dc.publication.volumen | 36 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 138 | es |
dc.publication.endPage | 146 | es |
dc.contributor.funder | Dirección General de Investigación (DGI). España | es |
dc.contributor.funder | Junta de Andalucía | es |
dc.contributor.funder | European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) | es |
dc.contributor.funder | Consejo Nacional de Ciencia y Tecnología (CONACYT). México | es |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (MICINN). España | es |
dc.contributor.funder | Agencia Estatal de Investigación. España | es |