Artículos (Química Orgánica)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/10924

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Examinando Artículos (Química Orgánica) por Agencia financiadora "Consejo Nacional de Ciencia y Tecnología (CONACYT). México"

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    Tuning the activity of iminosugars: novel N-alkylated deoxynojirimycin derivatives as strong BuChE inhibitors
    (Taylor & Francis Open Access, 2021) Ahuja Casarín, Ana I.; Merino Montiel, Penélope; Vega Báez, José Luis; Montiel Smith, Sara; Fernandes, Miguel X,; Lagunes, Irene; Maya Castilla, Inés; López López, Óscar; Fernández-Bolaños Guzmán, José María; Universidad de Sevilla. Departamento de Química orgánica; Dirección General de Investigación (DGI). España; Junta de Andalucía; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Consejo Nacional de Ciencia y Tecnología (CONACYT). México; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Agencia Estatal de Investigación. España; Universidad de Sevilla. FQM134: Química Fina de Carbohidratos
    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.