Toward the cholinesterase inhibition potential of TADDOL derivatives: Seminal biological and computational studies

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dc.article.numbere2200142
dc.catalogadorgjm
dc.contributor.authorConstantino, Andrea R.
dc.contributor.authorCharbe, Nitin Bharat
dc.contributor.authorDuarte, Yorley
dc.contributor.authorGutierrez, Margarita
dc.contributor.authorGiordano Villatoro, Ady
dc.contributor.authorPrasher, Parteek
dc.contributor.authorDua, Kamal
dc.contributor.authorMandolesi, Sandra
dc.contributor.authorZacconi, Flavia C. M.
dc.date.accessioned2023-08-24T20:16:52Z
dc.date.available2023-08-24T20:16:52Z
dc.date.issued2022
dc.description.abstractAlzheimer's disease (AD) is a degenerative neurological disease characterized by gradual loss of cognitive skills and memory. The exact pathogenesis involved still remains unrevealed, but several studies indicate the involvement of an array of different enzymes, underlining the multifactorial character of the disease. Inhibition of these enzymes is therefore a powerful approach in the development of AD treatments, with promising candidates, including acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase. Interestingly, AChE is the target of a major pesticide family (organophosphates), with several reports indicating an intersection between the pesticide's activity and AD. In this study, various TADDOL derivatives were synthesized and their in vitro activities as AChE/BuChE inhibitors as well as their antioxidant activities were studied. Molecular modeling studies revealed the capability of TADDOL derivatives to bind to AChE and induce inhibition, especially compounds 2b and 3c furnishing IC50 values of 36.78 +/- 8.97 and 59.23 +/- 5.31 mu M, respectively. Experimental biological activities and molecular modeling studies clearly demonstrate that TADDOL derivatives with specific stereochemistry have an interesting potential for the design of potent AChE inhibitors. The encouraging results for compounds 2b and 3c indicate them as promising scaffolds for selective and potent AChE inhibitors.
dc.fechaingreso.objetodigital2023-08-24
dc.format.extent14 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1002/ardp.202200142
dc.identifier.eissn1521-4184
dc.identifier.issn0365-6233
dc.identifier.urihttp://doi.org/10.1002/ardp.202200142
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/74489
dc.identifier.wosidWOS:000830293700001
dc.information.autorucEscuela de Química; Giordano Villatoro, Ady; S/I; 207712
dc.information.autorucEscuela de Química; Zacconi, Flavia C. M.; 0000-0002-3676-0453; 1011127
dc.issue.numero11
dc.language.isoen
dc.nota.accesoContenido parcial
dc.revistaArchiv der Pharmazie
dc.rightsacceso restringido
dc.subjectAcetylcholinesterase inhibitors
dc.subjectC-2 symmetry
dc.subjectMolecular modeling analysis
dc.subjectSelective AChE inhibitors
dc.subjectTADDOL derivatives
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleToward the cholinesterase inhibition potential of TADDOL derivatives: Seminal biological and computational studies
dc.typeartículo
dc.volumen355
sipa.codpersvinculados207712
sipa.codpersvinculados1011127
sipa.indexWOS
sipa.trazabilidadWOS;2022-10-11
sipa.trazabilidadORCID;2023-08-21
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