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dc.contributor.authorMarkowicz-Piasecka Magdalena
dc.contributor.authorSikora Joanna
dc.contributor.authorMateusiak Lukasz
dc.contributor.authorMikiciuk-Olasik Elzbieta
dc.contributor.authorHuttunen Kristiina M
dc.date.accessioned2017-12-14T12:00:24Z
dc.date.available2017-12-14T12:00:24Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/5076
dc.description.abstractThe results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM) may predispose to Alzheimer’s disease (AD). The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE) activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE) and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE) at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition) and BuChE (IC50 = 28 nmol/mL, mixed type inhibition), while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL). Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future.en
dc.language.isoENen
dc.publisherHindawi Limiteden
dc.relation.ispartofseriesOxidative Medicine and Cellular Longevityen
dc.relation.urihttp://dx.doi.org/10.1155/2017/7303096en
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/en
dc.titleMetformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activityen
dc.description.versionpublished versionen
dc.contributor.departmentSchool of Pharmacy, Activitiesen
uef.solecris.id49056457en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© Authorsen
dc.relation.doi10.1155/2017/7303096en
dc.description.reviewstatuspeerRevieweden
dc.relation.articlenumber7303096en
dc.relation.issn1942-0900en
dc.relation.volume2017en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
uef.solecris.openaccessOpen access -julkaisukanavassa ilmestynyt julkaisu


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