Structure-property studies of an imidazoquinoline chemotype with antitrypanosomal activity.

Autor:	Klug DM; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Diaz-Gonzalez R; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Cientificas , Granada 18016 , Spain., DeLano TJ; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Mavrogiannaki EM; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Buskes MJ; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Dalton RM; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Fisher JK; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Schneider KM; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Hilborne V; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Fritsche MG; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Simpson QJ; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Tear WF; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Devine WG; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Pérez-Moreno G; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Cientificas , Granada 18016 , Spain., Ceballos-Pérez G; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Cientificas , Granada 18016 , Spain., García-Hernández R; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Cientificas , Granada 18016 , Spain., Bosch-Navarrete C; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Cientificas , Granada 18016 , Spain., Ruiz-Pérez LM; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Cientificas , Granada 18016 , Spain., Gamarro F; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Cientificas , Granada 18016 , Spain., González-Pacanowska D; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Cientificas , Granada 18016 , Spain., Martinez-Martinez MS; Tres Cantos Medicines Development Campus , DDW and CIB , GlaxoSmithKline , Tres Cantos , Spain., Manzano-Chinchon P; Tres Cantos Medicines Development Campus , DDW and CIB , GlaxoSmithKline , Tres Cantos , Spain., Navarro M; Instituto de Parasitología y Biomedicina 'López-Neyra' Consejo Superior de Investigaciones Cientificas , Granada 18016 , Spain., Pollastri MP; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu., Ferrins L; Department of Chemistry & Chemical Biology , Northeastern University , 360 Huntington Avenue , Boston , MA 02115 , USA . Email: l.ferrins@northeastern.edu.
Jazyk:	angličtina
Zdroj:	RSC medicinal chemistry [RSC Med Chem] 2020 Jul 10; Vol. 11 (8), pp. 950-959. Date of Electronic Publication: 2020 Jul 10 (Print Publication: 2020).
DOI:	10.1039/d0md00103a
Abstrakt:	Human African trypanosomiasis is a neglected tropical disease (NTD) that is fatal if left untreated. Although approximately 13 million people live in moderate- to high-risk areas for infection, current treatments are plagued by problems with safety, efficacy, and emerging resistance. In an effort to fill the drug development pipeline for HAT, we have expanded previous work exploring the chemotype represented by the compound NEU-1090 , with a particular focus on improvement of absorption, distribution, metabolism and elimination (ADME) properties. These efforts resulted in several compounds with substantially improved aqueous solubility, although these modifications typically resulted in a loss of trypanosomal activity. We herein report the results of our investigation into the antiparasitic activity, toxicity, and ADME properties of this class of compounds in the interest of informing the NTD drug discovery community and avoiding duplication of effort. (This journal is © The Royal Society of Chemistry 2020.)
Databáze:	MEDLINE
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