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

A series of ferrocenyl and ruthenocenyl analogues of ferroquine have been synthesized and tested for efficacy against both chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum. To establish the role of the ferrocenyl moiety in the antiplasmodial activity of ferroquine, co...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2007-10, Vol.15 (20), p.6510-6516
Main Authors: Blackie, Margaret A.L., Beagley, Paul, Croft, Simon L., Kendrick, Howard, Moss, John R., Chibale, Kelly
Format: Article
Language:English
Subjects:
4-Aminoquinolines
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarial activity
Antimalarials - chemical synthesis
Antimalarials - chemistry
Antimalarials - pharmacology
Antiparasitic agents
Biological and medical sciences
Bioorganometallic
Chloroquine - chemistry
Chloroquine - pharmacology
Drug Resistance - drug effects
Ferroquine
Ferrous Compounds - chemistry
Medical sciences
Metallocene
Metallocenes
Molecular Structure
Organometallic Compounds - chemical synthesis
Organometallic Compounds - chemistry
Organometallic Compounds - pharmacology
Pharmacology. Drug treatments
Plasmodium falciparum - drug effects
Sensitivity and Specificity
Structure-Activity Relationship
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Summary:A series of ferrocenyl and ruthenocenyl analogues of ferroquine have been synthesized and tested for efficacy against both chloroquine-resistant and chloroquine-sensitive 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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2007.07.012