AI Article Synopsis
- Human African trypanosomiasis causes thousands of deaths annually in rural sub-Saharan Africa, with current treatments being ineffective and toxic.
- A triazine compound (UAMC-03011) was optimized for better pharmacokinetic properties and showed promising anti-trypanosomal activity without harming human cells.
- The study highlighted that understanding the rate of trypanocidal activity is crucial during the drug development process.
Article 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.
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| http://dx.doi.org/10.1016/j.ejmech.2018.03.048 | DOI Listing |
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