title: Synthesis and in vitro antiplasmodial evaluation of 4-anilino-2-trichloromethylquinazolines.
abstract: To identify a new safe antiplasmodial molecular scaffold, an original series of 2-trichloromethylquinazolines, functionalized in position 4 by an alkyl- or arylamino substituent, was synthesized from 4-chloro-2-trichloromethylquinazoline 1, via a cheap, fast and efficient solvent-free operating procedure. Among the 40 molecules prepared, several exhibit a good profile with both a significant antiplasmodial activity on the W2 Plasmodium falciparum strain (IC(50) values: 0.4-2.2 microM) and a promising toxicological behavior regarding human cells (HepG2/W2 selectivity indexes: 40-83), compared to the antimalarial drug compounds chloroquine and doxycycline. The in vitro antitoxoplasmic and antileishmanial evaluations were conducted in parallel on the most active molecules, showing that these ones specifically display antiplasmodial properties.
authors.affiliation: Laboratoire de Pharmacochimie Radicalaire, Faculté de Pharmacie, Universités d'Aix Marseille I, II et III-CNRS, UMR 6264, Marseille cedex 05, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Verhaeghe
authors.forename: Nadine
authors.initials: N
authors.lastname: Azas
authors.forename: Sébastien
authors.initials: S
authors.lastname: Hutter
authors.forename: Caroline
authors.initials: C
authors.lastname: Castera-Ducros
authors.forename: Michèle
authors.initials: M
authors.lastname: Laget
authors.forename: Aurélien
authors.initials: A
authors.lastname: Dumètre
authors.forename: Monique
authors.initials: M
authors.lastname: Gasquet
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Reboul
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
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014122:Toxoplasma / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000814:Aniline Compounds; D000962:Antimalarials; D011799:Quinazolines