edoc

In silico identification and in vitro activity of novel natural inhibitors of Trypanosoma brucei glyceraldehyde-3-phosphate-dehydrogenase

Herrmann, Fabian C. and Lenz, Mairin and Jose, Joachim and Kaiser, Marcel and Brun, Reto and Schmidt, Thomas J.. (2015) In silico identification and in vitro activity of novel natural inhibitors of Trypanosoma brucei glyceraldehyde-3-phosphate-dehydrogenase. Molecules, Vol. 20, H. 9. pp. 16154-16169.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6438874

Downloads: Statistics Overview

Abstract

As part of our ongoing efforts to identify natural products with activity against pathogens causing neglected tropical diseases, we are currently performing an extensive screening of natural product (NP) databases against a multitude of protozoan parasite proteins. Within this project, we screened a database of NPs from a commercial supplier, AnalytiCon Discovery (Potsdam, Germany), against Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH), a glycolytic enzyme whose inhibition deprives the parasite of energy supply. NPs acting as potential inhibitors of the mentioned enzyme were identified using a pharmacophore-based virtual screening and subsequent docking of the identified hits into the active site of interest. In a set of 700 structures chosen for the screening, 13 (1.9%) were predicted to possess significant affinity towards the enzyme and were therefore tested in an in vitro enzyme assay using recombinant TbGAPDH. Nine of these in silico hits (69%) showed significant inhibitory activity at 50 µM, of which two geranylated benzophenone derivatives proved to be particularly active with IC50 values below 10 µM. These compounds also showed moderate in vitro activity against T. brucei rhodesiense and may thus represent interesting starting points for further optimization.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Kaiser, Marcel and Brun, Reto
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:MDPI
ISSN:1420-3049
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:06 Nov 2015 10:21
Deposited On:06 Nov 2015 10:21

Repository Staff Only: item control page