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dc.contributor.authorBarbosa, Deyse B.
dc.contributor.authordo Bomfim, Mayra R.
dc.contributor.authorde Oliveira, Tiago A.
dc.contributor.authorda Silva, Alisson M.
dc.contributor.authorTaranto, Alex G.
dc.contributor.authorCruz, Jorddy N.
dc.contributor.authorde Carvalho, Paulo B.
dc.contributor.authorCampos Rosa, Joaquín María 
dc.contributor.authorRodrigues dos Santos, Cleydson Breno
dc.contributor.authorLeite, Franco H. A.
dc.date.accessioned2024-04-29T10:08:06Z
dc.date.available2024-04-29T10:08:06Z
dc.date.issued2023-11-28
dc.identifier.citationBarbosa, D.B.; do Bomfim, M.R.; de Oliveira, T.A.; da Silva, A.M.; Taranto, A.G.; Cruz, J.N.; de Carvalho, P.B.; Campos, J.M.; Santos, C.B.R.; Leite, F.H.A. Development of Potential Multi-Target Inhibitors for Human Cholinesterases and Beta-Secretase 1: A Computational Approach. Pharmaceuticals 2023, 16, 1657. https://doi.org/10.3390/ph16121657es_ES
dc.identifier.urihttps://hdl.handle.net/10481/91251
dc.description.abstractAlzheimer’s disease causes chronic neurodegeneration and is the leading cause of dementia in the world. The causes of this disease are not fully understood but seem to involve two essential cerebral pathways: cholinergic and amyloid. The simultaneous inhibition of AChE, BuChE, and BACE-1, essential enzymes involved in those pathways, is a promising therapeutic approach to treat the symptoms and, hopefully, also halt the disease progression. This study sought to identify triple enzymatic inhibitors based on stereo-electronic requirements deduced from molecular modeling of AChE, BuChE, and BACE-1 active sites. A pharmacophore model was built, displaying four hydrophobic centers, three hydrogen bond acceptors, and one positively charged nitrogen, and used to prioritize molecules found in virtual libraries. Compounds showing adequate overlapping rates with the pharmacophore were subjected to molecular docking against the three enzymes and those with an adequate docking score (n = 12) were evaluated for physicochemical and toxicological parameters and commercial availability. The structure exhibiting the greatest inhibitory potential against all three enzymes was subjected to molecular dynamics simulations (100 ns) to assess the stability of the inhibitor-enzyme systems. The results of this in silico approach indicate ZINC1733 can be a potential multi-target inhibitor of AChE, BuChE, and BACE-1, and future enzymatic assays are planned to validate those results.es_ES
dc.description.sponsorshipPPBE and PPGCF/UEFS; Fundação de Amparo à Pesquisa do Estado de Minas Gerais—FAPEMIG, grants APQ-02741-17, APQ-00855-19, APQ-01733-21, and APQ-04559-22es_ES
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq-Brazil, grants 305117/2017-3, 426261/2018-6es_ES
dc.description.sponsorshipFellowship of 2021 (grant 310108/2020-9)es_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAlzheimer’s diseasees_ES
dc.subjectMolecular dockinges_ES
dc.subjectMolecular dynamics es_ES
dc.titleDevelopment of Potential Multi-Target Inhibitors for Human Cholinesterases and Beta-Secretase 1: A Computational Approaches_ES
dc.typejournal articlees_ES
dc.rights.accessRightsopen accesses_ES
dc.identifier.doi10.3390/ph16121657
dc.type.hasVersionVoRes_ES


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