Gold compounds as cysteine protease inhibitors: perspectives for pharmaceutical application as antiparasitic agents
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Lara Massai
- Luigi Messori
- Nicola Micale
- Tanja Schirmeister
- Louis Maes
- Dolores Fregona
- Maria Agostina Cinellu
- Chiara Gabbiani
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000398709100015&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1007/s10534-017-0007-0
- eISSN
- 1572-8773
- Externe Identifier
- Clarivate Analytics Document Solution ID: ER3PI
- PubMed Identifier: 28283781
- ISSN
- 0966-0844
- Ausgabe der Veröffentlichung
- 2
- Zeitschrift
- BIOMETALS
- Schlüsselwörter
- Gold compounds
- Parasitic protozoa
- Cysteine proteases
- Enzyme inhibition
- Paginierung
- 313 - 320
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Titel
- Gold compounds as cysteine protease inhibitors: perspectives for pharmaceutical application as antiparasitic agents
- Sub types
- Article
- Ausgabe der Zeitschrift
- 30
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- Lara Massai
- Luigi Messori
- Nicola Micale
- Tanja Schirmeister
- Louis Maes
- Dolores Fregona
- Maria Agostina Cinellu
- Chiara Gabbiani
- DOI
- 10.1007/s10534-017-0007-0
- eISSN
- 1572-8773
- ISSN
- 0966-0844
- Ausgabe der Veröffentlichung
- 2
- Zeitschrift
- BioMetals
- Sprache
- en
- Online publication date
- 2017
- Paginierung
- 313 - 320
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1007/s10534-017-0007-0
- Datum der Datenerfassung
- 2019
- Titel
- Gold compounds as cysteine protease inhibitors: perspectives for pharmaceutical application as antiparasitic agents
- Ausgabe der Zeitschrift
- 30
Datenquelle: Crossref
- Abstract
- Gold compounds form a new class of promising metal-based drugs with a number of potential therapeutic applications, particularly in the fields of anticancer and antimicrobial treatments. Previous research revealed that a group of structurally diverse gold compounds cause conspicuous inhibition of the protease activities of the human proteasome. Given the pharmacological importance of protease inhibition, the present study further explored whether these gold compounds might inhibit a few other proteases that are accepted druggable targets for disease treatment. In particular, four distinct cysteine proteases were considered here: cathepsin B and L that play a primary role in tumor-cell invasion and metastasis; rhodesain, the major cathepsin L-like cysteine protease of Trypanosoma brucei rhodesiense and CPB2.8ΔCTE, a Leishmania mexicana mature cysteine protease. Based on the encouraging results obtained for some of the tested gold compounds on the two parasitic cysteine proteases, especially against CPB2.8ΔCTE, with IC<sub>50s</sub> in the micromolar range, we next evaluated whether those gold compounds might contrast effectively the growth of the respective protozoa and indeed important antiprotozoal properties were disclosed; on the other hand a certain lack of selectivity was highlighted. Also, no direct or clear correlation could be established between the in vitro antiprotozoal properties and the level of protease inhibition. The implications of these results are discussed in relation to possible pharmaceutical applications.
- Addresses
- (MetMed) Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy.
- Autoren
- Lara Massai
- Luigi Messori
- Nicola Micale
- Tanja Schirmeister
- Louis Maes
- Dolores Fregona
- Maria Agostina Cinellu
- Chiara Gabbiani
- DOI
- 10.1007/s10534-017-0007-0
- eISSN
- 1572-8773
- Externe Identifier
- PubMed Identifier: 28283781
- Funding acknowledgements
- Ente Cassa di Risparmio di Firenze:
- Open access
- false
- ISSN
- 0966-0844
- Ausgabe der Veröffentlichung
- 2
- Zeitschrift
- Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine
- Schlüsselwörter
- Cell Line
- Fibroblasts
- Macrophages
- Animals
- Humans
- Mice
- Plasmodium falciparum
- Leishmania infantum
- Trypanosoma brucei brucei
- Trypanosoma brucei rhodesiense
- Trypanosoma cruzi
- Proteasome Endopeptidase Complex
- Cathepsin B
- Cysteine Endopeptidases
- Protozoan Proteins
- Recombinant Proteins
- Cysteine Proteinase Inhibitors
- Antiprotozoal Agents
- Inhibitory Concentration 50
- Organogold Compounds
- Cathepsin L
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2017
- Paginierung
- 313 - 320
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Datum der Datenerfassung
- 2017
- Titel
- Gold compounds as cysteine protease inhibitors: perspectives for pharmaceutical application as antiparasitic agents.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 30
Datenquelle: Europe PubMed Central
- Abstract
- Gold compounds form a new class of promising metal-based drugs with a number of potential therapeutic applications, particularly in the fields of anticancer and antimicrobial treatments. Previous research revealed that a group of structurally diverse gold compounds cause conspicuous inhibition of the protease activities of the human proteasome. Given the pharmacological importance of protease inhibition, the present study further explored whether these gold compounds might inhibit a few other proteases that are accepted druggable targets for disease treatment. In particular, four distinct cysteine proteases were considered here: cathepsin B and L that play a primary role in tumor-cell invasion and metastasis; rhodesain, the major cathepsin L-like cysteine protease of Trypanosoma brucei rhodesiense and CPB2.8ΔCTE, a Leishmania mexicana mature cysteine protease. Based on the encouraging results obtained for some of the tested gold compounds on the two parasitic cysteine proteases, especially against CPB2.8ΔCTE, with IC50s in the micromolar range, we next evaluated whether those gold compounds might contrast effectively the growth of the respective protozoa and indeed important antiprotozoal properties were disclosed; on the other hand a certain lack of selectivity was highlighted. Also, no direct or clear correlation could be established between the in vitro antiprotozoal properties and the level of protease inhibition. The implications of these results are discussed in relation to possible pharmaceutical applications.
- Date of acceptance
- 2017
- Autoren
- Lara Massai
- Luigi Messori
- Nicola Micale
- Tanja Schirmeister
- Louis Maes
- Dolores Fregona
- Maria Agostina Cinellu
- Chiara Gabbiani
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/28283781
- DOI
- 10.1007/s10534-017-0007-0
- eISSN
- 1572-8773
- Ausgabe der Veröffentlichung
- 2
- Zeitschrift
- Biometals
- Schlüsselwörter
- Cysteine proteases
- Enzyme inhibition
- Gold compounds
- Parasitic protozoa
- Animals
- Antiprotozoal Agents
- Cathepsin B
- Cathepsin L
- Cell Line
- Cysteine Endopeptidases
- Cysteine Proteinase Inhibitors
- Fibroblasts
- Humans
- Inhibitory Concentration 50
- Leishmania infantum
- Macrophages
- Mice
- Organogold Compounds
- Plasmodium falciparum
- Proteasome Endopeptidase Complex
- Protozoan Proteins
- Recombinant Proteins
- Trypanosoma brucei brucei
- Trypanosoma brucei rhodesiense
- Trypanosoma cruzi
- Sprache
- eng
- Country
- Netherlands
- Paginierung
- 313 - 320
- PII
- 10.1007/s10534-017-0007-0
- Datum der Veröffentlichung
- 2017
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2017
- Titel
- Gold compounds as cysteine protease inhibitors: perspectives for pharmaceutical application as antiparasitic agents.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 30
Datenquelle: PubMed
- Beziehungen:
- Eigentum von