Metallocene-based antimalarials: an exploration into the influence of the ferrocenyl moiety on in vitro antimalarial activity in chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum.
To establish the role of the ferrocenyl moiety in the antiplasmodial activity of ferroquine, compounds in which this moiety is replaced by the corresponding ruthenium-based moieties were synthesized and evaluated. In both the sensitive (D10) and resistant (K1) strains of Plasmodium falciparum, ruthenoquine analogues showed comparable potency to ferroquine. This suggests that a probable role of the ferrocenyl fragment is to serve simply as a hydrophobic spacer group. In addition, ferroquine analogues with different aromatic substituents were synthesized and evaluated. Unexpectedly high activity for quinoline compounds lacking the 7-chloro substituent suggests the ferrocenyl moiety may have an additive and/or synergistic effect.
Blackie
Margaret A L
MA
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
Beagley
Paul
P
Croft
Simon L
SL
Kendrick
Howard
H
Moss
John R
JR
Chibale
Kelly
K
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002738:Chloroquine / Q000737:chemistry / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects; D005296:Ferrous Compounds / Q000737:chemistry*; D000075163:Metallocenes; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
D000962:Antimalarials; D005296:Ferrous Compounds; D000075163:Metallocenes; D009942:Organometallic Compounds; C013108:metallocene; D002738:Chloroquine; C004998:ferrocene