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Antimalarial pyrido[1,2-a]benzimidazoles : lead optimization, parasite life cycle stage profile, mechanistic evaluation, killing kinetics, and in vivo oral efficacy in a mouse model

Singh, Kawaljit and Okombo, John and Brunschwig, Christel and Ndubi, Ferdinand and Barnard, Linley and Wilkinson, Chad and Njogu, Peter M. and Njoroge, Mathew and Laing, Lizahn and Machado, Marta and Prudêncio, Miguel and Reader, Janette and Botha, Mariette and Nondaba, Sindisiwe and Birkholtz, Lyn-Marie and Lauterbach, Sonja and Churchyard, Alisje and Coetzer, Theresa L. and Burrows, Jeremy N. and Yeates, Clive and Denti, Paolo and Wiesner, Lubbe and Egan, Timothy J. and Wittlin, Sergio and Chibale, Kelly. (2017) Antimalarial pyrido[1,2-a]benzimidazoles : lead optimization, parasite life cycle stage profile, mechanistic evaluation, killing kinetics, and in vivo oral efficacy in a mouse model. Journal of medicinal chemistry, 60 (4). pp. 1432-1448.

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Official URL: http://edoc.unibas.ch/54815/

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Abstract

Further structure-activity relationship (SAR) studies on the recently identified pyrido[1,2-a]benzimidazole (PBI) antimalarials have led to the identification of potent, metabolically stable compounds with improved in vivo oral efficacy in the P. berghei mouse model and additional activity against parasite liver and gametocyte stages, making them potential candidates for preclinical development. Inhibition of hemozoin formation possibly contributes to the mechanism of action.
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 (MPI) > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Wittlin, Sergio
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
ISSN:0022-2623
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:20 Oct 2017 05:53
Deposited On:29 May 2017 12:05

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