Discovery of highly selective 7-chloroquinoline-thiohydantoins with potent antimalarial activity.
Basic Information
ID: ALA3351876
Journal: Eur J Med Chem
Title: Discovery of highly selective 7-chloroquinoline-thiohydantoins with potent antimalarial activity.
Authors: Raj R, Mehra V, Gut J, Rosenthal PJ, Wicht KJ, Egan TJ, Hopper M, Wrischnik LA, Land KM, Kumar V.
Abstract: A series of C-3 thiourea functionalized β-lactams, β-lactam-7-chloroquinoline conjugates and 7-chloroquinoline-thiohydantoin derivatives were prepared with the aim of probing antimalarial structure-activity relationships. 7-Chlorquinoline-thiohydantoin derivatives were found to be potent inhibitors of cultured Plasmodium falciparum, with the most potent and non-cytotoxic compound exhibiting an IC50 of 39.8 nM. Studies of β-hematin formation suggested that inhibition of haemozoin formation could be primary mechanism of action, with IC50 values comparable to those of chloroquine. Evaluation of cytotoxicity against HeLa cells demonstrated high selective indices.
CiteXplore: 25038484
DOI: 10.1016/j.ejmech.2014.07.048
Patent ID: ┄