title: 4-Thiophenoxy-2-trichloromethyquinazolines display in vitro selective antiplasmodial activity against the human malaria parasite Plasmodium falciparum.
abstract: A series of original quinazolines bearing a 4-thiophenoxy and a 2-trichloromethyl group was synthesized in a convenient and efficient way and was evaluated toward its in vitro antiplasmodial potential. The series revealed global good activity against the K1-multi-resistant Plasmodium falciparum strain, especially with hit compound 5 (IC(50)=0.9 μM), in comparison with chloroquine and doxycycline chosen as reference-drugs. Both the in vitro cytotoxicity study which was conducted on the human HepG2 cell line and the in vitro antitoxoplasmic screening against Toxoplasma gondii indicate that this series presents an interesting selective antiplasmodial profile. Structure-activity- and toxicity relationships highlight that the trichloromethyl group plays a key role in the antiplasmodial activity and also show that the modulation of the thiophenol moiety influences the toxicity/activity ratio.
authors.affiliation: Laboratoire de Pharmacochimie Radicalaire, Faculté de Pharmacie, Universités d'Aix-Marseille I, II et III - UMR CNRS 6264, Laboratoire Chimie Provence, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Verhaeghe
authors.forename: Aurélien
authors.initials: A
authors.lastname: Dumètre
authors.forename: Caroline
authors.initials: C
authors.lastname: Castera-Ducros
authors.forename: Sébastien
authors.initials: S
authors.lastname: Hutter
authors.forename: Michèle
authors.initials: M
authors.lastname: Laget
authors.forename: Cyril
authors.initials: C
authors.lastname: Fersing
authors.forename: Marion
authors.initials: M
authors.lastname: Prieri
authors.forename: Julien
authors.initials: J
authors.lastname: Yzombard
authors.forename: France
authors.initials: F
authors.lastname: Sifredi
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rault
authors.forename: Pascal
authors.initials: P
authors.lastname: Rathelot
authors.forename: Patrice
authors.initials: P
authors.lastname: Vanelle
authors.forename: Nadine
authors.initials: N
authors.lastname: Azas
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004351:Drug Resistance; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009152:Mutagenicity Tests; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D011799:Quinazolines