October N., Watermeyer N.D., Yardley V., Egan T.J., Ncokazi K., Chibale K.
Reversed chloroquines based on the 3,4-dihydropyrimidin-2(1H)-one scaffold: Synthesis and evaluation for antimalarial, β-haematin inhibition, and cytotoxic activity
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa; Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
October, N., Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Watermeyer, N.D., Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Yardley, V., Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; Egan, T.J., Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Ncokazi, K., Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Chibale, K., Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa
(Chemical Equation Presented) The synthesis, cytotoxicity, and antimalarial activity of resistance-reversing bifunctional dihydropyrimidone-chloroquinoline conjugates are reported herein. In vitro assay results indicate this class of compounds is highly active against both chloroquine-resistant and chloroquine-sensitive strains of P. falciparum. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.
antimalarial agent; chloroquine; hemoprotein; hemozoin; pyrimidine derivative; animal; article; biological model; chemical model; chemical structure; chemistry; drug antagonism; drug design; IC 50; metabolism; methodology; nuclear magnetic resonance spectroscopy; structure activity relation; synthesis; Animals; Antimalarials; Chemistry, Pharmaceutical; Chloroquine; Drug Design; Hemeproteins; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Models, Biological; Models, Chemical; Molecular Structure; Pyrimidines; Structure-Activity Relationship