Synthesis, Antimalarial Activity, and Structure-Activity Relationship of 7-(2-Phenoxyethoxy)-4(1H)-quinolones
| Autor: | Lisa Luong, R. Matthew Cross, Tina S. Mutka, Roman Manetsch, Dennis E. Kyle, Niranjan K. Namelikonda |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Plasmodium falciparum
Drug Resistance Drug resistance Pharmacology Quinolones Article Cell Line Antimalarials Mice Structure-Activity Relationship Drug Discovery medicine Structure–activity relationship Animals ED50 Atovaquone EC50 biology Chemistry biology.organism_classification medicine.disease Multiple drug resistance Molecular Medicine Malaria medicine.drug |
| Zdroj: | J Med Chem |
| Popis: | ICI 56,780 (5) displayed causal prophylactic and blood schizonticidal activity (ED(50) = 0.05 mg/kg) in rodent malaria models, but produced rapid acquisition of parasitological resistance in P. berghei infected mice.(1) Herein we describe the synthesis of analogs of 5 with EC(50)s as low as 0.15 nM against multi-drug resistant P. falciparum. Optimal activity with low cross resistance indexes (RI) to atovaquone were achieved by introducing ortho-substituted aryl moieties at the 3-position of the 7-(2-phenoxyethoxy)-4(1H)-quinolone core. |
| Databáze: | OpenAIRE |
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