Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/27923
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dc.contributor.authorCarreiro, Elisabete P.-
dc.contributor.authorLouro, Patrícia-
dc.contributor.authorAdriano, Gizé-
dc.contributor.authorGuedes, Romina A.-
dc.contributor.authorVannuchi, Nicholas-
dc.contributor.authorCosta, Ana R.-
dc.contributor.authorAntunes, Célia M. M.-
dc.contributor.authorGuedes, Rita C.-
dc.contributor.authorBurke, A. J.-
dc.date.accessioned2014-12-16T14:01:48Z-
dc.date.available2014-12-16T14:01:48Z-
dc.date.issued2014-06-
dc.identifier.citationCARREIRO, Elisabete P. [et. al] - 3-Hydroxypyrrolidine and (3,4)-dihydroxypyrrolidine derivatives: inhibition of rat intestinal α-glucosidase. "Bioorganic Chemistry". ISSN 0045-2068. Vol. 54 (2014) p. 81–88por
dc.identifier.issn0045-2068-
dc.identifier.urihttp://hdl.handle.net/10316/27923-
dc.description.abstractThirteen pyrrolidine-based iminosugar derivatives have been synthesized and evaluated for inhibition of α-glucosidase from rat intestine. The compounds studied were the non-hydroxy, mono-hydroxy and dihydroxypyrrolidines. All the compounds were N-benzylated apart from one. Four of the compounds had a carbonyl group in the 2,5-position of the pyrrolidine ring. The most promising iminosugar was the trans-3,4-dihydroxypyrrolidine 5 giving an IC50 of 2.97 ± 0.046 and a KI of 1.18 mM. Kinetic studies showed that the inhibition was of the mixed type, but predominantly competitive for all the compounds tested. Toxicological assay results showed that the compounds have low toxicity. Docking studies showed that all the compounds occupy the same region as the DNJ inhibitor on the enzyme binding site with the most active compounds establishing similar interactions with key residues. Our studies suggest that a rotation of ∼90° of some compounds inside the binding pocket is responsible for the complete loss of inhibitory activity. Despite the fact that activity was found only in the mM range, these compounds have served as simple molecular tools for probing the structural features of the enzyme, so that inhibition can be improved in further studies.por
dc.language.isoengpor
dc.publisherElsevierpor
dc.rightsopenAccesspor
dc.subject1-Benzyl-3-hydroxypyrrolidinepor
dc.subject1-Benzyl-3,4-dihydroxypyrrolidinepor
dc.subjectSmall molecule inhibitorpor
dc.subjectα-Glucosidasepor
dc.subjectRat intestinal cellspor
dc.title3-Hydroxypyrrolidine and (3,4)-dihydroxypyrrolidine derivatives: inhibition of rat intestinal α-glucosidasepor
dc.typearticlepor
degois.publication.firstPage81por
degois.publication.lastPage88por
degois.publication.titleBioorganic Chemistrypor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0045206814000315por
dc.peerreviewedYespor
dc.identifier.doi10.1016/j.bioorg.2014.04.007-
degois.publication.volume54por
item.grantfulltextopen-
item.languageiso639-1en-
item.fulltextCom Texto completo-
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
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