Combined Chemical, Biological and Theoretical DFT‐QTAIM Study of Potent Glycosidase Inhibitors Based on Quaternary Indolizinium Salts
Identifieur interne : 000591 ( France/Analysis ); précédent : 000590; suivant : 000592Combined Chemical, Biological and Theoretical DFT‐QTAIM Study of Potent Glycosidase Inhibitors Based on Quaternary Indolizinium Salts
Auteurs : Peter Šafá ; Jozefína Žúžiová ; Štefan Marchalín [Slovaquie] ; Nadežda Pr Nayová [Slovaquie] ; Ubomír Švorc [Slovaquie] ; Viktor Vrábel [Slovaquie] ; Sergej Šesták [Slovaquie] ; Dubravko Rendi [Autriche] ; Vincent Tognetti [France] ; Laurent Joubert ; Adam Daïch [France]Source :
- European Journal of Organic Chemistry [ 1434-193X ] ; 2012-10.
English descriptors
- KwdEn :
Abstract
Six novel enantiopure epimeric indolizidinediols have been easily prepared in high yields by an effective and well‐established regioselective THF ring‐opening reaction as a key step. Quarternization of these species was also studied and comparison was made to the quaternizations of other substituted indolizidines. Importantly, a combined theoretical DFT‐QTAIM study has cast light on the various factors that explain the observed conformational selectivity. The inhibitory properties of the six synthesized indolizidines were then investigated against the recombinant Golgi α‐mannosidase‐IIb (dGMIIb) and lysosomal α‐mannosidase (dLM408), human homologues of Drosophila melanogaster. Among the tested compounds, two of them, 4a and 4b, exhibited a pH‐dependent inhibition of dGMIIb at the milimolar level (IC50 = 3.5 or 1.7 mM at pH 5.8 or 6.5, respectively) without affecting the activity of dLM408.
Url:
DOI: 10.1002/ejoc.201200431
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 001031
- to stream Istex, to step Curation: 001031
- to stream Istex, to step Checkpoint: 000072
- to stream Main, to step Merge: 000673
- to stream Main, to step Curation: 000673
- to stream Main, to step Exploration: 000673
- to stream France, to step Extraction: 000591
Links to Exploration step
ISTEX:E61BE7EDC52CBE6B6D57B11E6F06655D84CB06DALe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Combined Chemical, Biological and Theoretical DFT‐QTAIM Study of Potent Glycosidase Inhibitors Based on Quaternary Indolizinium Salts</title><author><name sortKey="Safa, Peter" sort="Safa, Peter" uniqKey="Safa P" first="Peter" last="Šafá">Peter Šafá</name></author><author><name sortKey="Zuziova, Jozefina" sort="Zuziova, Jozefina" uniqKey="Zuziova J" first="Jozefína" last="Žúžiová">Jozefína Žúžiová</name></author><author><name sortKey="Marchalin, Stefan" sort="Marchalin, Stefan" uniqKey="Marchalin S" first="Štefan" last="Marchalín">Štefan Marchalín</name></author><author><name sortKey="Pr Nayova, Nadezda" sort="Pr Nayova, Nadezda" uniqKey="Pr Nayova N" first="Nadežda" last="Pr Nayová">Nadežda Pr Nayová</name></author><author><name sortKey="Svorc, Ubomir" sort="Svorc, Ubomir" uniqKey="Svorc " first=" Ubomír" last="Švorc"> Ubomír Švorc</name></author><author><name sortKey="Vrabel, Viktor" sort="Vrabel, Viktor" uniqKey="Vrabel V" first="Viktor" last="Vrábel">Viktor Vrábel</name></author><author><name sortKey="Sestak, Sergej" sort="Sestak, Sergej" uniqKey="Sestak S" first="Sergej" last="Šesták">Sergej Šesták</name></author><author><name sortKey="Rendi, Dubravko" sort="Rendi, Dubravko" uniqKey="Rendi D" first="Dubravko" last="Rendi">Dubravko Rendi</name></author><author><name sortKey="Tognetti, Vincent" sort="Tognetti, Vincent" uniqKey="Tognetti V" first="Vincent" last="Tognetti">Vincent Tognetti</name></author><author><name sortKey="Joubert, Laurent" sort="Joubert, Laurent" uniqKey="Joubert L" first="Laurent" last="Joubert">Laurent Joubert</name></author><author><name sortKey="Daich, Adam" sort="Daich, Adam" uniqKey="Daich A" first="Adam" last="Daïch">Adam Daïch</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:E61BE7EDC52CBE6B6D57B11E6F06655D84CB06DA</idno><date when="2012" year="2012">2012</date><idno type="doi">10.1002/ejoc.201200431</idno><idno type="url">https://api.istex.fr/document/E61BE7EDC52CBE6B6D57B11E6F06655D84CB06DA/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001031</idno><idno type="wicri:Area/Istex/Curation">001031</idno><idno type="wicri:Area/Istex/Checkpoint">000072</idno><idno type="wicri:doubleKey">1434-193X:2012:Safa P:combined:chemical:biological</idno><idno type="wicri:Area/Main/Merge">000673</idno><idno type="wicri:Area/Main/Curation">000673</idno><idno type="wicri:Area/Main/Exploration">000673</idno><idno type="wicri:Area/France/Extraction">000591</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Combined Chemical, Biological and Theoretical DFT‐QTAIM Study of Potent Glycosidase Inhibitors Based on Quaternary Indolizinium Salts</title><author><name sortKey="Safa, Peter" sort="Safa, Peter" uniqKey="Safa P" first="Peter" last="Šafá">Peter Šafá</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField">http://www.chtf.stuba.sk/koch/marchalin/prof_marchalin.html</wicri:noCountry></affiliation></author><author><name sortKey="Zuziova, Jozefina" sort="Zuziova, Jozefina" uniqKey="Zuziova J" first="Jozefína" last="Žúžiová">Jozefína Žúžiová</name><affiliation><wicri:noCountry code="subField">http://www.chtf.stuba.sk/koch/marchalin/prof_marchalin.html</wicri:noCountry></affiliation></author><author><name sortKey="Marchalin, Stefan" sort="Marchalin, Stefan" uniqKey="Marchalin S" first="Štefan" last="Marchalín">Štefan Marchalín</name><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Slovaquie</country></affiliation></author><author><name sortKey="Pr Nayova, Nadezda" sort="Pr Nayova, Nadezda" uniqKey="Pr Nayova N" first="Nadežda" last="Pr Nayová">Nadežda Pr Nayová</name><affiliation wicri:level="1"><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Central Laboratories Faculty of Chemical & Food Technology, University of Technology, Radlinského 9, 81237 Bratislava</wicri:regionArea><wicri:noRegion>81237 Bratislava</wicri:noRegion></affiliation></author><author><name sortKey="Svorc, Ubomir" sort="Svorc, Ubomir" uniqKey="Svorc " first=" Ubomír" last="Švorc"> Ubomír Švorc</name><affiliation wicri:level="1"><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Analytical Chemistry, Faculty of Chemical & Food Technology, University of Technology, Radlinského 9, 81237 Bratislava</wicri:regionArea><wicri:noRegion>81237 Bratislava</wicri:noRegion></affiliation></author><author><name sortKey="Vrabel, Viktor" sort="Vrabel, Viktor" uniqKey="Vrabel V" first="Viktor" last="Vrábel">Viktor Vrábel</name><affiliation wicri:level="1"><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Analytical Chemistry, Faculty of Chemical & Food Technology, University of Technology, Radlinského 9, 81237 Bratislava</wicri:regionArea><wicri:noRegion>81237 Bratislava</wicri:noRegion></affiliation></author><author><name sortKey="Sestak, Sergej" sort="Sestak, Sergej" uniqKey="Sestak S" first="Sergej" last="Šesták">Sergej Šesták</name><affiliation wicri:level="1"><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravská cesta 9, 84538 Bratislava</wicri:regionArea><wicri:noRegion>84538 Bratislava</wicri:noRegion></affiliation></author><author><name sortKey="Rendi, Dubravko" sort="Rendi, Dubravko" uniqKey="Rendi D" first="Dubravko" last="Rendi">Dubravko Rendi</name><affiliation wicri:level="3"><country xml:lang="fr">Autriche</country><wicri:regionArea>Department für Chemie, Universität für Bodenkultur, Muthgasse 18, 1190 Wien</wicri:regionArea><placeName><region type="land" nuts="2">Vienne (Autriche)</region><settlement type="city">Vienne (Autriche)</settlement></placeName></affiliation></author><author><name sortKey="Tognetti, Vincent" sort="Tognetti, Vincent" uniqKey="Tognetti V" first="Vincent" last="Tognetti">Vincent Tognetti</name><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation></author><author><name sortKey="Joubert, Laurent" sort="Joubert, Laurent" uniqKey="Joubert L" first="Laurent" last="Joubert">Laurent Joubert</name><affiliation><wicri:noCountry code="subField">http://ircof.crihan.fr/V2/rubrique.php3?id_rubrique=144</wicri:noCountry></affiliation></author><author><name sortKey="Daich, Adam" sort="Daich, Adam" uniqKey="Daich A" first="Adam" last="Daïch">Adam Daïch</name><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation></author></analytic><monogr></monogr><series><title level="j">European Journal of Organic Chemistry</title><title level="j" type="abbrev">Eur. J. Org. Chem.</title><idno type="ISSN">1434-193X</idno><idno type="eISSN">1099-0690</idno><imprint><publisher>WILEY‐VCH Verlag</publisher><pubPlace>Weinheim</pubPlace><date type="published" when="2012-10">2012-10</date><biblScope unit="volume">2012</biblScope><biblScope unit="issue">28</biblScope><biblScope unit="page" from="5498">5498</biblScope><biblScope unit="page" to="5514">5514</biblScope></imprint><idno type="ISSN">1434-193X</idno></series><idno type="istex">E61BE7EDC52CBE6B6D57B11E6F06655D84CB06DA</idno><idno type="DOI">10.1002/ejoc.201200431</idno><idno type="ArticleID">EJOC201200431</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1434-193X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biological activity</term><term>Conformation analysis</term><term>Density functional calculations</term><term>Enzyme inhibitors</term><term>Natural products</term><term>Nitrogen heterocycles</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Six novel enantiopure epimeric indolizidinediols have been easily prepared in high yields by an effective and well‐established regioselective THF ring‐opening reaction as a key step. Quarternization of these species was also studied and comparison was made to the quaternizations of other substituted indolizidines. Importantly, a combined theoretical DFT‐QTAIM study has cast light on the various factors that explain the observed conformational selectivity. The inhibitory properties of the six synthesized indolizidines were then investigated against the recombinant Golgi α‐mannosidase‐IIb (dGMIIb) and lysosomal α‐mannosidase (dLM408), human homologues of Drosophila melanogaster. Among the tested compounds, two of them, 4a and 4b, exhibited a pH‐dependent inhibition of dGMIIb at the milimolar level (IC50 = 3.5 or 1.7 mM at pH 5.8 or 6.5, respectively) without affecting the activity of dLM408.</div></front></TEI><affiliations><list><country><li>Autriche</li><li>France</li><li>Slovaquie</li></country><region><li>Vienne (Autriche)</li></region><settlement><li>Vienne (Autriche)</li></settlement></list><tree><noCountry><name sortKey="Joubert, Laurent" sort="Joubert, Laurent" uniqKey="Joubert L" first="Laurent" last="Joubert">Laurent Joubert</name><name sortKey="Safa, Peter" sort="Safa, Peter" uniqKey="Safa P" first="Peter" last="Šafá">Peter Šafá</name><name sortKey="Zuziova, Jozefina" sort="Zuziova, Jozefina" uniqKey="Zuziova J" first="Jozefína" last="Žúžiová">Jozefína Žúžiová</name></noCountry><country name="Slovaquie"><noRegion><name sortKey="Marchalin, Stefan" sort="Marchalin, Stefan" uniqKey="Marchalin S" first="Štefan" last="Marchalín">Štefan Marchalín</name></noRegion><name sortKey="Pr Nayova, Nadezda" sort="Pr Nayova, Nadezda" uniqKey="Pr Nayova N" first="Nadežda" last="Pr Nayová">Nadežda Pr Nayová</name><name sortKey="Sestak, Sergej" sort="Sestak, Sergej" uniqKey="Sestak S" first="Sergej" last="Šesták">Sergej Šesták</name><name sortKey="Svorc, Ubomir" sort="Svorc, Ubomir" uniqKey="Svorc " first=" Ubomír" last="Švorc"> Ubomír Švorc</name><name sortKey="Vrabel, Viktor" sort="Vrabel, Viktor" uniqKey="Vrabel V" first="Viktor" last="Vrábel">Viktor Vrábel</name></country><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Rendi, Dubravko" sort="Rendi, Dubravko" uniqKey="Rendi D" first="Dubravko" last="Rendi">Dubravko Rendi</name></region></country><country name="France"><noRegion><name sortKey="Tognetti, Vincent" sort="Tognetti, Vincent" uniqKey="Tognetti V" first="Vincent" last="Tognetti">Vincent Tognetti</name></noRegion><name sortKey="Daich, Adam" sort="Daich, Adam" uniqKey="Daich A" first="Adam" last="Daïch">Adam Daïch</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/France/explor/LeHavreV1/Data/France/Analysis
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000591 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/France/Analysis/biblio.hfd -nk 000591 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/France
|area= LeHavreV1
|flux= France
|étape= Analysis
|type= RBID
|clé= ISTEX:E61BE7EDC52CBE6B6D57B11E6F06655D84CB06DA
|texte= Combined Chemical, Biological and Theoretical DFT‐QTAIM Study of Potent Glycosidase Inhibitors Based on Quaternary Indolizinium Salts
}}
| This area was generated with Dilib version V0.6.25. |  |