Publication
Title
Optimization of the pharmacokinetic properties of potent anti-trypanosomal triazine derivatives
Author
Abstract
Human African trypanosomiasis is causing thousands of deaths every year in the rural areas of sub-saharan Africa. There is a high unmet medical need since the approved drugs are poorly efficacious, show considerable toxicity and are not easy to administer. This work describes the optimization of the pharmacokinetic properties of a previously published family of triazine lead compounds. One compound (35 (UAMC-03011)) with potent anti-trypanosomal activity and no cytotoxicity was selected for further study because of its good microsomal stability and high selectivity for Trypanosoma brucei over a panel including Trypanosoma cruzi, L.eishmania infantum, and Plasmodium falciparum. In vivo pharmacokinetic parameters were determined and the compound was studied in an acute in vivo mouse disease model. One of the important learnings of this study was that the rate of trypanocidal activity is an important parameter during the lead optimization process.
Language
English
Source (journal)
European journal of medicinal chemistry. - Paris, 1974, currens
Publication
Paris : 2018
ISSN
0223-5234
Volume/pages
151 (2018) , p. 18-26
ISI
000432640900003
Pubmed ID
29604541
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Project info
Optimization of novel lead compounds for the treatment of African trypanosomiasis using innovative medicinal chemistry and formulation.
Dynamics and mechanisms of paromomycin and miltefosine drug-resistance in the protozoan parasite Leishmania.
Identifying factors involved in miltefosine or amphotericin B treatment failure in visceral leishmaniasis.
Veterinary and human parasitology.
INFLA-MED - Fundamental research in the pathophysiological processes of inflammatory diseases.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 09.04.2018
Last edited 15.11.2022
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