title: Design, synthesis, and antimalarial activity of structural chimeras of thiosemicarbazone and ferroquine analogues.
abstract: The design, synthesis, and antimalarial activity of chimeras of thiosemicarbazones (TSC) and ferroquine (FQ) is reported. Key structural elements derived from FQ were coupled to fragments capable of coordinating metal ions. Biological evaluation was conducted against four strains of the malaria parasite Plasmodium falciparum and against the parasitic cysteine protease falcipain-2. To establish the role of the ferrocenyl moiety in the antiplasmodial activity of this series, purely organic parent compounds were also synthesized and tested. The presence of the aminoquinoline structure, allowing transport of the compounds to the food vacuole of the parasite, seems to be the major contributor to antimalarial activity.
authors.affiliation: Université des Sciences et Technologies, Unité de Catalyse et de Chimie du Solide-UMR CNRS 8181, ENSCL, Bâtiment C7, BP 90108, 59652 Villeneuve d'Ascq Cedex, France. christophe.biot@ensc-lille.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Biot
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Sergeant
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D000075163:Metallocenes; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D005296:Ferrous Compounds; D000075163:Metallocenes; D013882:Thiosemicarbazones; C479230:ferroquine; D003546:Cysteine Endopeptidases; C416224:falcipain 2