In vitro phenotypic screening of 7-chloro-4-amino(oxy)quinoline derivatives as putative anti-Trypanosoma cruzi agents |
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| Institution: | 1. CEI Campus Moncloa, UCM-UPM & CSIC, Madrid, Spain;2. Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, Pza. Ramón y Cajal s/n, 28040 Madrid, Spain;3. Laboratorio de Química Orgánica y Biomolecular, Escuela de Química, Universidad Industrial de Santander, A.A. 678 Bucaramanga, Colombia;1. Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia;2. Faculty of Chemistry, University of Belgrade, P.O. Box 51, 11158 Belgrade, Serbia;1. Infection Control Programme and WHO Collaborating Centre on Patient Safety—Infection Control and Improving Practices, University of Geneva Hospitals and Faculty of Medicine, 1205 Geneva, Switzerland;2. Department of Infectious Diseases, Centro Hospitalar Lisboa Norte and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal;1. Department of Gastroenterology, Kochi Medical School, Kochi, Japan;2. Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy;3. Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia;4. Istituto di Biochimica delle Proteine—CNR, Via P. Castellino 111, 80131 Napoli, Italy;5. Università degli Studi di Firenze, Polo Scientifico, Dipartimento di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy |
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| Abstract: | In this study, a series of 22 pre-synthesized 7-chloro-4-amino(oxy)quinoline derivatives was assayed in vitro as potential antichagasic agents. A primary screening against Trypanosoma cruzi epimastigotes and a non-specific cytotoxicity assay on murine fibroblasts were simultaneously performed, resulting quinolines 3, 7 and 12 with great selectivity (SI) on the extracellular parasite (SI7, SI3, SI12 and SIBZ >9.44). Therefore, the activity of these derivatives was evaluated on intracellular amastigotes, achieving derivative 7 the best SI (SI = 12.73). These results, supported by the in silico prediction of a good oral bioavailability and a suitable risk profile, propose the 4-amino-7-chloroquinoline scaffold as a potential template for designing trypanocidal prototypes. |
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| Keywords: | Chloroquinoline derivatives Cytotoxicity Lipinski’s rule OSIRIS software |
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