2. Academic Validation
  3. Synthesis, antimalarial activity, and structure-activity relationship of 7-(2-phenoxyethoxy)-4(1H)-quinolones

Synthesis, antimalarial activity, and structure-activity relationship of 7-(2-phenoxyethoxy)-4(1H)-quinolones

  • J Med Chem. 2011 Dec 22;54(24):8321-7. doi: 10.1021/jm200718m.
R Matthew Cross 1,  Niranjan K Namelikonda,  Tina S Mutka,  Lisa Luong,  Dennis E Kyle,  Roman Manetsch
Affiliations

Affiliation

  • 1 Department of Chemistry, University of South Florida, CHE 205, 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
PMID: 22111907 DOI: 10.1021/jm200718m
Abstract

ICI 56,780 (5) displayed causal prophylactic and blood schizonticidal activity (ED50=0.05 mg/kg) in rodent malaria models but produced rapid acquisition of parasitological resistance in P. berghei infected mice. Herein we describe the synthesis of analogues of 5 with EC50 as low as 0.15 nM against multidrug resistant P. falciparum. Optimal activity with low cross-resistance indexes (RI) to atovaquone was achieved by introducing ortho-substituted aryl moieties at the 3-position of the 7-(2-phenoxyethoxy)-4(1H)-quinolone core.

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