Investigation into novel thiophene- and furan-based 4-amino-7-chloroquinolines afforded antimalarials that cure mice
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Sciotti, Richard J.
Pybus, Brandon S.
Šolaja, Bogdan A.
Article (Published version)
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We herein report the design and synthesis of a novel series of thiophene-and furan-based aminoquinoline derivatives which were found to be potent antimalarials and inhibitors of b-hematin polymerization. Tested compounds were 3-71 times more potent in vitro than CQ against chloroquine-resistant (CQR) W2 strain with benzonitrile 30 being as active as mefloquine (MFQ), and almost all synthesized aminoquinolines (22/27) were more potent than MFQ against multidrug-resistant (MDR) strain C235. In vivo experiments revealed that compound 28 showed clearance with recrudescence at 40 mg/kg/day, while 5/5 mice survived in Thompson test at 160 mg/kg/day.
Keywords:Malaria / Thiophene / Furan / Aminoquinoline inhibitors / P. berghei / Chemotherapy / Cytotoxicity / beta-Hematin polymerization inhibitors
Source:Bioorganic and Medicinal Chemistry, 2015, 23, 9, 2176-2186
- Pergamon-Elsevier Science Ltd, Oxford
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
- Control of infections by Apicomplexan pathogens: from novel drug targets to prediction (RS-41019)
- Serbian Academy of Sciences and Arts
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3381