Antivirulence Isoquinolone Mannosides: Optimization of the Biaryl Aglycone for FimH Lectin Binding Affinity and Efficacy in the Treatment of Chronic UTI
| العنوان: | Antivirulence Isoquinolone Mannosides: Optimization of the Biaryl Aglycone for FimH Lectin Binding Affinity and Efficacy in the Treatment of Chronic UTI |
|---|---|
| المؤلفون: | James W. Janetka, Laurel Mydock-McGrane, Jerome S. Pinkner, Vasilios Kalas, Zhenfu Han, Corinne K. Cusumano, Jana Binkley, Bradley Ford, Roger D. Klein, Cassie M. Jarvis, Zachary T. Cusumano, Scott J. Hultgren |
| المصدر: | ChemMedChem. 11(4) |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Mannosides, Hemagglutination, medicine.drug_class, Stereochemistry, 030106 microbiology, Urinary Bladder, Carboxamide, Biochemistry, Article, 03 medical and health sciences, chemistry.chemical_compound, Drug Discovery, medicine, Potency, Humans, Uropathogenic Escherichia coli, General Pharmacology, Toxicology and Pharmaceutics, Escherichia coli Infections, Pharmacology, Adhesins, Escherichia coli, Chemistry, Organic Chemistry, Biofilm, Rational design, Isoquinolines, Anti-Bacterial Agents, Bacterial adhesin, Molecular Docking Simulation, 030104 developmental biology, Aglycone, Chronic Disease, Urinary Tract Infections, Molecular Medicine, Fimbriae Proteins |
| الوصف: | Uropathogenic E. coli (UPEC) employ the mannose-binding adhesin FimH to colonize the bladder epithelium during urinary tract infection (UTI). Previously reported FimH antagonists exhibit good potency and efficacy, but low bioavailability and a short half-life in vivo. In a rational design strategy, we obtained an X-ray structure of lead mannosides and then designed mannosides with improved drug-like properties. We show that cyclizing the carboxamide onto the biphenyl B-ring aglycone of biphenyl mannosides into a fused heterocyclic ring, generates new biaryl mannosides such as isoquinolone 22 (2-methyl-4-(1-oxo-1,2-dihydroisoquinolin-7-yl)phenyl α-d-mannopyranoside) with enhanced potency and in vivo efficacy resulting from increased oral bioavailability. N-Substitution of the isoquinolone aglycone with various functionalities produced a new potent subseries of FimH antagonists. All analogues of the subseries have higher FimH binding affinity than unsubstituted lead 22, as determined by thermal shift differential scanning fluorimetry assay. Mannosides with pyridyl substitution on the isoquinolone group inhibit bacteria-mediated hemagglutination and prevent biofilm formation by UPEC with single-digit nanomolar potency, which is unprecedented for any FimH antagonists or any other antivirulence compounds reported to date. |
| تدمد: | 1860-7187 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0870168f07aa020437a9a39095c673b1 https://pubmed.ncbi.nlm.nih.gov/26812660 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0870168f07aa020437a9a39095c673b1 |
| قاعدة البيانات: | OpenAIRE |
| ResultId |
1 |
|---|---|
| Header |
edsair OpenAIRE edsair.doi.dedup.....0870168f07aa020437a9a39095c673b1 790 3 unknown 790.477966308594 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsair&AN=edsair.doi.dedup.....0870168f07aa020437a9a39095c673b1&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0870168f07aa020437a9a39095c673b1# [Name] => EDS - OpenAIRE [Category] => fullText [Text] => View record in OpenAIRE [MouseOverText] => View record in OpenAIRE ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Antivirulence Isoquinolone Mannosides: Optimization of the Biaryl Aglycone for FimH Lectin Binding Affinity and Efficacy in the Treatment of Chronic UTI
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22James+W%2E+Janetka%22">James W. Janetka</searchLink><br /><searchLink fieldCode="AR" term="%22Laurel+Mydock-McGrane%22">Laurel Mydock-McGrane</searchLink><br /><searchLink fieldCode="AR" term="%22Jerome+S%2E+Pinkner%22">Jerome S. Pinkner</searchLink><br /><searchLink fieldCode="AR" term="%22Vasilios+Kalas%22">Vasilios Kalas</searchLink><br /><searchLink fieldCode="AR" term="%22Zhenfu+Han%22">Zhenfu Han</searchLink><br /><searchLink fieldCode="AR" term="%22Corinne+K%2E+Cusumano%22">Corinne K. Cusumano</searchLink><br /><searchLink fieldCode="AR" term="%22Jana+Binkley%22">Jana Binkley</searchLink><br /><searchLink fieldCode="AR" term="%22Bradley+Ford%22">Bradley Ford</searchLink><br /><searchLink fieldCode="AR" term="%22Roger+D%2E+Klein%22">Roger D. Klein</searchLink><br /><searchLink fieldCode="AR" term="%22Cassie+M%2E+Jarvis%22">Cassie M. Jarvis</searchLink><br /><searchLink fieldCode="AR" term="%22Zachary+T%2E+Cusumano%22">Zachary T. Cusumano</searchLink><br /><searchLink fieldCode="AR" term="%22Scott+J%2E+Hultgren%22">Scott J. Hultgren</searchLink> ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => <i>ChemMedChem</i>. 11(4) ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2016 ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%220301+basic+medicine%22">0301 basic medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Mannosides%22">Mannosides</searchLink><br /><searchLink fieldCode="DE" term="%22Hemagglutination%22">Hemagglutination</searchLink><br /><searchLink fieldCode="DE" term="%22medicine%2Edrug%5Fclass%22">medicine.drug_class</searchLink><br /><searchLink fieldCode="DE" term="%22Stereochemistry%22">Stereochemistry</searchLink><br /><searchLink fieldCode="DE" term="%22030106+microbiology%22">030106 microbiology</searchLink><br /><searchLink fieldCode="DE" term="%22Urinary+Bladder%22">Urinary Bladder</searchLink><br /><searchLink fieldCode="DE" term="%22Carboxamide%22">Carboxamide</searchLink><br /><searchLink fieldCode="DE" term="%22Biochemistry%22">Biochemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Article%22">Article</searchLink><br /><searchLink fieldCode="DE" term="%2203+medical+and+health+sciences%22">03 medical and health sciences</searchLink><br /><searchLink fieldCode="DE" term="%22chemistry%2Echemical%5Fcompound%22">chemistry.chemical_compound</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+Discovery%22">Drug Discovery</searchLink><br /><searchLink fieldCode="DE" term="%22medicine%22">medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Potency%22">Potency</searchLink><br /><searchLink fieldCode="DE" term="%22Humans%22">Humans</searchLink><br /><searchLink fieldCode="DE" term="%22Uropathogenic+Escherichia+coli%22">Uropathogenic Escherichia coli</searchLink><br /><searchLink fieldCode="DE" term="%22General+Pharmacology%2C+Toxicology+and+Pharmaceutics%22">General Pharmacology, Toxicology and Pharmaceutics</searchLink><br /><searchLink fieldCode="DE" term="%22Escherichia+coli+Infections%22">Escherichia coli Infections</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmacology%22">Pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22Adhesins%2C+Escherichia+coli%22">Adhesins, Escherichia coli</searchLink><br /><searchLink fieldCode="DE" term="%22Chemistry%22">Chemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Organic+Chemistry%22">Organic Chemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Biofilm%22">Biofilm</searchLink><br /><searchLink fieldCode="DE" term="%22Rational+design%22">Rational design</searchLink><br /><searchLink fieldCode="DE" term="%22Isoquinolines%22">Isoquinolines</searchLink><br /><searchLink fieldCode="DE" term="%22Anti-Bacterial+Agents%22">Anti-Bacterial Agents</searchLink><br /><searchLink fieldCode="DE" term="%22Bacterial+adhesin%22">Bacterial adhesin</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+Docking+Simulation%22">Molecular Docking Simulation</searchLink><br /><searchLink fieldCode="DE" term="%22030104+developmental+biology%22">030104 developmental biology</searchLink><br /><searchLink fieldCode="DE" term="%22Aglycone%22">Aglycone</searchLink><br /><searchLink fieldCode="DE" term="%22Chronic+Disease%22">Chronic Disease</searchLink><br /><searchLink fieldCode="DE" term="%22Urinary+Tract+Infections%22">Urinary Tract Infections</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+Medicine%22">Molecular Medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Fimbriae+Proteins%22">Fimbriae Proteins</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => Uropathogenic E. coli (UPEC) employ the mannose-binding adhesin FimH to colonize the bladder epithelium during urinary tract infection (UTI). Previously reported FimH antagonists exhibit good potency and efficacy, but low bioavailability and a short half-life in vivo. In a rational design strategy, we obtained an X-ray structure of lead mannosides and then designed mannosides with improved drug-like properties. We show that cyclizing the carboxamide onto the biphenyl B-ring aglycone of biphenyl mannosides into a fused heterocyclic ring, generates new biaryl mannosides such as isoquinolone 22 (2-methyl-4-(1-oxo-1,2-dihydroisoquinolin-7-yl)phenyl α-d-mannopyranoside) with enhanced potency and in vivo efficacy resulting from increased oral bioavailability. N-Substitution of the isoquinolone aglycone with various functionalities produced a new potent subseries of FimH antagonists. All analogues of the subseries have higher FimH binding affinity than unsubstituted lead 22, as determined by thermal shift differential scanning fluorimetry assay. Mannosides with pyridyl substitution on the isoquinolone group inhibit bacteria-mediated hemagglutination and prevent biofilm formation by UPEC with single-digit nanomolar potency, which is unprecedented for any FimH antagonists or any other antivirulence compounds reported to date. ) Array ( [Name] => ISSN [Label] => ISSN [Group] => ISSN [Data] => 1860-7187 ) Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0870168f07aa020437a9a39095c673b1" linkWindow="_blank">https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0870168f07aa020437a9a39095c673b1</link><br /><link linkTarget="URL" linkTerm="https://pubmed.ncbi.nlm.nih.gov/26812660" linkWindow="_blank">https://pubmed.ncbi.nlm.nih.gov/26812660</link> ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => OPEN ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsair.doi.dedup.....0870168f07aa020437a9a39095c673b1 ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Languages] => Array
(
[0] => Array
(
[Text] => Undetermined
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => 0301 basic medicine
[Type] => general
)
[1] => Array
(
[SubjectFull] => Mannosides
[Type] => general
)
[2] => Array
(
[SubjectFull] => Hemagglutination
[Type] => general
)
[3] => Array
(
[SubjectFull] => medicine.drug_class
[Type] => general
)
[4] => Array
(
[SubjectFull] => Stereochemistry
[Type] => general
)
[5] => Array
(
[SubjectFull] => 030106 microbiology
[Type] => general
)
[6] => Array
(
[SubjectFull] => Urinary Bladder
[Type] => general
)
[7] => Array
(
[SubjectFull] => Carboxamide
[Type] => general
)
[8] => Array
(
[SubjectFull] => Biochemistry
[Type] => general
)
[9] => Array
(
[SubjectFull] => Article
[Type] => general
)
[10] => Array
(
[SubjectFull] => 03 medical and health sciences
[Type] => general
)
[11] => Array
(
[SubjectFull] => chemistry.chemical_compound
[Type] => general
)
[12] => Array
(
[SubjectFull] => Drug Discovery
[Type] => general
)
[13] => Array
(
[SubjectFull] => medicine
[Type] => general
)
[14] => Array
(
[SubjectFull] => Potency
[Type] => general
)
[15] => Array
(
[SubjectFull] => Humans
[Type] => general
)
[16] => Array
(
[SubjectFull] => Uropathogenic Escherichia coli
[Type] => general
)
[17] => Array
(
[SubjectFull] => General Pharmacology, Toxicology and Pharmaceutics
[Type] => general
)
[18] => Array
(
[SubjectFull] => Escherichia coli Infections
[Type] => general
)
[19] => Array
(
[SubjectFull] => Pharmacology
[Type] => general
)
[20] => Array
(
[SubjectFull] => Adhesins, Escherichia coli
[Type] => general
)
[21] => Array
(
[SubjectFull] => Chemistry
[Type] => general
)
[22] => Array
(
[SubjectFull] => Organic Chemistry
[Type] => general
)
[23] => Array
(
[SubjectFull] => Biofilm
[Type] => general
)
[24] => Array
(
[SubjectFull] => Rational design
[Type] => general
)
[25] => Array
(
[SubjectFull] => Isoquinolines
[Type] => general
)
[26] => Array
(
[SubjectFull] => Anti-Bacterial Agents
[Type] => general
)
[27] => Array
(
[SubjectFull] => Bacterial adhesin
[Type] => general
)
[28] => Array
(
[SubjectFull] => Molecular Docking Simulation
[Type] => general
)
[29] => Array
(
[SubjectFull] => 030104 developmental biology
[Type] => general
)
[30] => Array
(
[SubjectFull] => Aglycone
[Type] => general
)
[31] => Array
(
[SubjectFull] => Chronic Disease
[Type] => general
)
[32] => Array
(
[SubjectFull] => Urinary Tract Infections
[Type] => general
)
[33] => Array
(
[SubjectFull] => Molecular Medicine
[Type] => general
)
[34] => Array
(
[SubjectFull] => Fimbriae Proteins
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Antivirulence Isoquinolone Mannosides: Optimization of the Biaryl Aglycone for FimH Lectin Binding Affinity and Efficacy in the Treatment of Chronic UTI
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => James W. Janetka
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Laurel Mydock-McGrane
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Jerome S. Pinkner
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Vasilios Kalas
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Zhenfu Han
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Corinne K. Cusumano
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Jana Binkley
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Bradley Ford
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Roger D. Klein
)
)
)
[9] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Cassie M. Jarvis
)
)
)
[10] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Zachary T. Cusumano
)
)
)
[11] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Scott J. Hultgren
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 05
[M] => 01
[Type] => published
[Y] => 2016
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-print
[Value] => 18607187
)
[1] => Array
(
[Type] => issn-locals
[Value] => edsair
)
[2] => Array
(
[Type] => issn-locals
[Value] => edsairFT
)
)
[Numbering] => Array
(
[0] => Array
(
[Type] => volume
[Value] => 11
)
[1] => Array
(
[Type] => issue
[Value] => 4
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => ChemMedChem
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |