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Optimization of the electrophile of chloronitrobenzamide leads active against Trypanosoma brucei

Hwang, Jong Yeon and Smithson, David C. and Holbrook, Gloria and Zhu, Fangyi and Connelly, Michele C. and Kaiser, Marcel and Brun, Reto and Kiplin Guy, R.. (2013) Optimization of the electrophile of chloronitrobenzamide leads active against Trypanosoma brucei. Bioorganic & medicinal chemistry letters : a Tetrahedron publication for the rapid dissemination of preliminary communications on all aspects of bioorganic chemistry, medicinal chemistry, bioinorganic chemistry and related disciplines, Vol. 23, H. 14. pp. 4127-4131.

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Official URL: http://edoc.unibas.ch/dok/A6164969

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Abstract

We previously reported the phenylchloronitrobenzamides (PCNBs), a novel class of compounds active against the species of trypanosomes that cause Human African Trypanosomiasis (HAT). Herein, we explored the potential to adjust the reactivity of the electrophilic chloronitrobenzamide core. These studies identified compound 7d that potently inhibited the growth of trypanosomes (EC50=120nM for Trypanosoma b. brucei, 18nM for Trypanosoma b. rhodesiense, and 38nM for Trypanosoma b. gambiense) without significant cytotoxicity against mammalian cell lines (EC50<25μM for HepG2, HEK293, Raji, and BJ cell lines) and also had good stability in microsomal models (t1/2<4h in both human and mouse). Overall these properties indicate the compound 7d and its analogs are worth further exploration as potential leads for HAT.
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:Brun, Reto and Kaiser, Marcel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0960-894X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Jan 2014 09:49
Deposited On:31 Jan 2014 09:49

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