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In vitro and In vivo evaluation of 28DAP010, a novel diamidine for treatment of second-stage African sleeping sickness

Wenzler, Tanja and Yang, Sihyung and Patrick, Donald A. and Braissant, Olivier and Ismail, Mohamed A. and Tidwell, Richard R. and Boykin, David W. and Wang, Michael Zhuo and Brun, Reto. (2014) In vitro and In vivo evaluation of 28DAP010, a novel diamidine for treatment of second-stage African sleeping sickness. Antimicrobial agents and chemotherapy, Vol. 58, H. 8. pp. 4452-4463.

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Official URL: http://edoc.unibas.ch/dok/A6289127

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Abstract

African sleeping sickness is a neglected tropical disease transmitted by tsetse flies. New and better drugs are still needed especially for its second stage, which is fatal if untreated. 28DAP010, a dipyridylbenzene analogue of DB829, is the second simple diamidine found to cure mice with central nervous system infections by a parenteral route of administration. 28DAP010 showed efficacy similar to that of DB829 in dose-response studies in mouse models of first- and second-stage African sleeping sickness. The in vitro time to kill, determined by microcalorimetry, and the parasite clearance time in mice were shorter for 28DAP010 than for DB829. No cross-resistance was observed between 28DAP010 and pentamidine on the tested Trypanosoma brucei gambiense isolates from melarsoprol-refractory patients. 28DAP010 is the second promising preclinical candidate among the diamidines for the treatment of second-stage African sleeping sickness.
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:Wenzler, Tanja and Brun, Reto
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:0066-4804
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Nov 2014 08:28
Deposited On:07 Nov 2014 08:28

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