Title:4-Aminoquinoline-ferrocene Hybrids as Potential Antimalarials
Volume: 15
Issue: 2
Author(s): Xhamla Nqoro and Blessing A. Aderibigbe*
Affiliation:
- Department of Chemistry, University of Fort Hare, Alice Campus, Alice,South Africa
Keywords:
Ferrocene, Plasmodium falciparum, 4-aminoquinoline, esterification reaction, hybrid compound,
malaria.
Abstract: Background: Malaria is a deadly disease. It is mostly treated using 4-
aminoquinoline derivatives such as chloroquine etc. because it is well-tolerated, displays
low toxicity, and after administration, it is rapidly absorbed. The combination of
4-aminoquinoline with other classes of antimalarial drugs has been reported to be an
effective approach for the treatment of malaria. Furthermore, some patents reported
hybrids 4-aminoquinolines containing ferrocene moiety with potent antimalarial activity.
Objective: The objective of the current study is to prepare 4-aminoquinoline-ferrocene
hybrids via esterification and amidation reactions. The compounds were characterized via
FTIR, LC-MS and NMR spectroscopy. In vitro screening against chloroquine-sensitive
P. falciparum parasite (NF54) at concentrations (1 μM and 5 μM) and an inhibitory concentration
(full dose-response) was studied.
Methods: The compounds were prepared via known reactions and monitored by Thin
Layer Chromatography. The compounds were purified by column chromatography and
characterized using FTIR, NMR and MS. In vitro antiplasmodial evaluation was performed
against asexual parasite and chloroquine was used as a reference drug.
Results: The percentage inhibition effects of the hybrid compounds were in a range of
97.9-102% at 5 μM and 36-96% at 1 μM. Furthermore, the IC50 values of the compounds
were in the range of 0.7-1.6 μM when compared to the parent drug,
4-ferrocenylketobutanoic acid.
Conclusion: The hybrid compounds displayed significant antimalarial activity when
compared to the parent drug. However, they were not as effective as chloroquine on the
drug-sensitive parasite. The findings revealed that 4-aminoquinolines and ferrocene are
potential scaffolds for developing potent antimalarials.
