Synthetic ferrocenic mefloquine and quinine analoguesas potential antimalarial agents.
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.
Biot
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C
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.
Delhaes
L
L
Maciejewski
L A
LA
Mortuaire
M
M
Camus
D
D
Dive
D
D
Brocard
J S
JS
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
D000962:Antimalarials; D005296:Ferrous Compounds; D000075163:Metallocenes; D011803:Quinine; D015767:Mefloquine; C004998:ferrocene