Flavones as isosteres of 4(1H)-quinolones: Discovery of ligand efficient and dual stage antimalarial lead compounds

Malaria is responsible for nearly one million deaths annually, and the increasing prevalence of multi-resistant strains of Plasmodium falciparum poses a great challenge to controlling the disease. A diverse set of flavones, isosteric to 4(1H)-quinolones, were prepared and profiled for their antiplasmodial activity against the blood stage of P. falciparum W2 strain, and the liver stage of the rodent parasite Plasmodium berghei. Ligand efficient leads were identified as dual stage antimalarials, suggesting that scaffold optimization may afford potent antiplasmodial compounds.

Tiago Rodrigues a, Ana S. Ressurreição a, Filipa P. da Cruz b, Inês S. Albuquerque b, Jiri Gut c, Marta P. Carrasco a, Daniel Gonçalves a, Rita C. Guedes a, Daniel J.V.A. dos Santos a, d, Maria M. Mota b, Philip J. Rosenthal c, Rui Moreira a, Miguel Prudêncio b, Francisca Lopes a

a Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-019 Lisbon,

b Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal

c Department of Medicine, San Francisco General Hospital, University of California, San Francisco, Box 0811, San Francisco, CA 94143, USA

d REQUIMTE, Department of Chemistry & Biochemistry, Faculty of Sciences, University of Porto, R. do Campo Alegre, 4169-007 Porto, Portugal


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