title: Synthetic ferrocenic mefloquine and quinine analoguesas potential antimalarial agents.
abstract: A few years ago we proposed a strategy for the synthesis of new ferrocene-chloroquine analogues replacing the carbon chain of chloroquine by hydrophobic ferrocenyl moieties. Now, this strategy has been applied to the antimalarial amino-alcohols class to afford new potentially active analogues of mefloquine and quinine bearing a substituted ferrocenic group. The pathway used for the synthesis of the mefloquine analogues includes the coupling of an aminomethyl substituted ferrocene carboxaldehyde with a lithio quinoline compound. On the other hand, the synthesis of quinine analogues was ensured by the 'inverse' reaction of a lithio aminomethyl ferrocene with a quinoline carboxaldehyde. The configurations of each diastereoisomer were unambiguously determined by spectroscopic data. The mechanistic interpretations were fully discussed. Ferrocenyl analogues of mefloquine and quinine exhibited a lower antimalarial activity than mefloquine and quinine themselves. Comparing optical isomers, those isomers dissimilar to ferrocenyl derivatives presented better antimalarial activities than those similar to ferrocenyl.
authors.affiliation: Laboratoire de catalyse de Lille, groupe de synthèse organométallique, UPRESA 8010, école nationale supérieure de chimie de Lille, bâtiment C7 université des sciences et technologies BP 108, Villeneuve, France.
authors.forename: C
authors.initials: C
authors.lastname: Biot
authors.forename: L
authors.initials: L
authors.lastname: Delhaes
authors.forename: L A
authors.initials: LA
authors.lastname: Maciejewski
authors.forename: M
authors.initials: M
authors.lastname: Mortuaire
authors.forename: D
authors.initials: D
authors.lastname: Camus
authors.forename: D
authors.initials: D
authors.lastname: Dive
authors.forename: J S
authors.initials: JS
authors.lastname: Brocard
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015767:Mefloquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000075163:Metallocenes; D010963:Plasmodium falciparum / Q000187:drug effects; D011803:Quinine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D005296:Ferrous Compounds; D000075163:Metallocenes; D011803:Quinine; D015767:Mefloquine; C004998:ferrocene