Structure-property studies of an imidazoquinoline chemotype with antitrypanosomal activity
| Autor: | Miguel Navarro, Quillon J. Simpson, Travis J. DeLano, Maria Santos Martinez-Martinez, Raquel García-Hernández, Rosario Diaz-Gonzalez, Westley Tear, Guiomar Pérez-Moreno, William G. Devine, Lori Ferrins, Dolores González-Pacanowska, Luis M. Ruiz-Pérez, Melanie G. Fritsche, Katherine M. Schneider, Michael P. Pollastri, Francisco Gamarro, John K. Fisher, Cristina Bosch-Navarrete, Pilar Manzano-Chinchon, Vivian Hilborne, Dana M. Klug, Raeann M. Dalton, Gloria Ceballos-Pérez, Eftychia M. Mavrogiannaki, Melissa J. Buskes |
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| Rok vydání: | 2020 |
| Předmět: |
Pharmaceutical Science
Biology Pharmacology 01 natural sciences Biochemistry 03 medical and health sciences chemistry.chemical_compound Drug Discovery medicine African trypanosomiasis 030304 developmental biology ADME 0303 health sciences Chemotype Drug discovery Organic Chemistry Structure property Tropical disease medicine.disease 0104 chemical sciences Imidazoquinoline Chemistry 010404 medicinal & biomolecular chemistry Drug development chemistry Molecular Medicine |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Digital.CSIC: Repositorio Institucional del CSIC Consejo Superior de Investigaciones Científicas (CSIC) RSC Med Chem |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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