Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine protease of Trypanosoma brucei
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Tanja Schirmeister
- Janina Schmitz
- Sascha Jung
- Torsten Schmenger
- R Luise Krauth-Siegel
- Michael Guetschow
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000395771100010&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.bmcl.2016.11.036
- eISSN
- 1464-3405
- Externe Identifier
- Clarivate Analytics Document Solution ID: EN1LH
- PubMed Identifier: 27890381
- ISSN
- 0960-894X
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
- Schlüsselwörter
- Dipeptide nitrile
- Cysteine protease
- Rhodesain
- Inhibitor
- Trypanosoma
- Paginierung
- 45 - 50
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Titel
- Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine protease of <i>Trypanosoma brucei</i>
- Sub types
- Article
- Ausgabe der Zeitschrift
- 27
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- Tanja Schirmeister
- Janina Schmitz
- Sascha Jung
- Torsten Schmenger
- R Luise Krauth-Siegel
- Michael Gütschow
- DOI
- 10.1016/j.bmcl.2016.11.036
- ISSN
- 0960-894X
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Bioorganic & Medicinal Chemistry Letters
- Sprache
- en
- Paginierung
- 45 - 50
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.bmcl.2016.11.036
- Datum der Datenerfassung
- 2022
- Titel
- Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine protease of Trypanosoma brucei
- Ausgabe der Zeitschrift
- 27
Datenquelle: Crossref
- Abstract
- A series of dipeptide nitriles known as inhibitors of mammalian cathepsins were evaluated for inhibition of rhodesain, the cathepsin L-like protease of Trypanosoma brucei. Compound 35 consisting of a Leu residue fitting into the S2 pocket and a triarylic moiety consisting of thiophene, a 1,2,4-oxadiazole and a phenyl ring fitting into the S3 pocket, and compound 33 with a 3-bromo-Phe residue (S2) and a biphenyl fragment (S3) were found to inhibit rhodesain in the single-digit nanomolar range. The observed steep structure-activity relationship could be explained by covalent docking simulations. With their high selectivity indices (ca. 200) and the good antitrypanosomal activity (8μM) the compounds represent promising starting points for new rhodesain inhibitors.
- Addresses
- Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University, Staudingerweg 5, 55128 Mainz, Germany. Electronic address: schirmei@uni-mainz.de.
- Autoren
- Tanja Schirmeister
- Janina Schmitz
- Sascha Jung
- Torsten Schmenger
- R Luise Krauth-Siegel
- Michael Gütschow
- DOI
- 10.1016/j.bmcl.2016.11.036
- eISSN
- 1464-3405
- Externe Identifier
- PubMed Identifier: 27890381
- Open access
- false
- ISSN
- 0960-894X
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Bioorganic & medicinal chemistry letters
- Schlüsselwörter
- Trypanosoma brucei brucei
- Nitriles
- Cysteine Endopeptidases
- Dipeptides
- Cysteine Proteinase Inhibitors
- Antitubercular Agents
- Molecular Structure
- Structure-Activity Relationship
- Dose-Response Relationship, Drug
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2016
- Paginierung
- 45 - 50
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Datum der Datenerfassung
- 2016
- Titel
- Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine protease of Trypanosoma brucei.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 27
Datenquelle: Europe PubMed Central
- Abstract
- A series of dipeptide nitriles known as inhibitors of mammalian cathepsins were evaluated for inhibition of rhodesain, the cathepsin L-like protease of Trypanosoma brucei. Compound 35 consisting of a Leu residue fitting into the S2 pocket and a triarylic moiety consisting of thiophene, a 1,2,4-oxadiazole and a phenyl ring fitting into the S3 pocket, and compound 33 with a 3-bromo-Phe residue (S2) and a biphenyl fragment (S3) were found to inhibit rhodesain in the single-digit nanomolar range. The observed steep structure-activity relationship could be explained by covalent docking simulations. With their high selectivity indices (ca. 200) and the good antitrypanosomal activity (8μM) the compounds represent promising starting points for new rhodesain inhibitors.
- Date of acceptance
- 2016
- Autoren
- Tanja Schirmeister
- Janina Schmitz
- Sascha Jung
- Torsten Schmenger
- R Luise Krauth-Siegel
- Michael Gütschow
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/27890381
- DOI
- 10.1016/j.bmcl.2016.11.036
- eISSN
- 1464-3405
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Bioorg Med Chem Lett
- Schlüsselwörter
- Cysteine protease
- Dipeptide nitrile
- Inhibitor
- Rhodesain
- Trypanosoma
- Antitubercular Agents
- Cysteine Endopeptidases
- Cysteine Proteinase Inhibitors
- Dipeptides
- Dose-Response Relationship, Drug
- Molecular Structure
- Nitriles
- Structure-Activity Relationship
- Trypanosoma brucei brucei
- Sprache
- eng
- Country
- England
- Paginierung
- 45 - 50
- PII
- S0960-894X(16)31177-5
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2017
- Titel
- Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine protease of Trypanosoma brucei.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 27
Datenquelle: PubMed
- Beziehungen:
- Eigentum von