In Vitro Antimalarial Activity of a New Organometallic Analog, Ferrocene-Chloroquine

Abstract

The in vitro activities of new organometallic chloroquine analogs, based on 4-amino-quinoleine compounds bound to a molecule of ferrocene, were evaluated against chloroquine-susceptible, chloroquine-intermediate, and chloroquine-resistant, culture-adaptedPlasmodium falciparum lineages by a proliferation test. One of the ferrocene analogs totally restored the activity of chloroquine against chloroquine-resistant parasites. This compound, associated with tartaric acid for better solubility, was highly effective. The role of the ferrocene in reversing chloroquine resistance is discussed, as is its potential use for human therapy.

In vitro and in vivo antimalarial activity of ferrochloroquine, a ferrocenyl analogue of chloroquine against chloroquine-resistant malaria parasites

“…The in vitro FQ activity was more striking against resistant P. falciparum strains (FCR3 and Dd2) than against the chloroquine-susceptible strain HB3. In vivo, FQ was shown to have an appreciable antimalarial activity against P. berghei N. Those data con®rmed preliminary published results (Biot et al 1997(Biot et al , 1999aDomarle et al 1998).…”

“…It is already known that many quinoline derivatives are capable of overcoming chloroquine resistance (De et al 1998;Kotecka et al 1997;Ridley et al 1996), although some level of cross-resistance may be involved (Ridley et al 1996). So far, no cross-resistance has been observed between FQ and chloroquine (Domarle et al 1998). The present work strengthens this hypothesis.…”

“…Recently, dicyclopentadienyl iron analogues of chloroquine have been shown to be eective against malaria parasites (Biot et al 1997(Biot et al , 1999aDomarle et al 1998). The present work con®rms the in vitro and in vivo activity of ferrochloroquine (the most potent derivative) on chloroquine-resistant strains and describes both the curative eect on P. vinckei vinckei and preliminary investigations on its toxicity.…”

Recent developments in the design and synthesis of hybrid molecules basedon aminoquinoline ring and their antiplasmodial evaluation

“…Besides short chain CQ derivatives, several aminoquinoline metal complexes have been screened against resistant strains of P. falciparum. Of these complexes, ferroquine (30a) shows the greatest promise, and clinical trials are currently in progress with this candidate [128,129]. The presence of a bulk ferrocenyl moiety (hydrophobic group) in the alkyl side chain of CQ-analogues has a positive effect on the efficacy of these compounds in CQ-resistant strains of P. falciparum.…”

Synthesis, Crystal Structure and Thermal Properties of N-Acetyl-3-(2-furyl)-5-ferrocenyl-2-pyrazoline and N-Acetyl-3-(2-thienyl)-5-ferrocenyl-2-pyrazoline

“…Ferrocene is often incorporated into organic compounds in order to obtain novel, enhanced or unexpected biological activities due to unique structure, different membrane-permeation properties and anomalous metabolism [18][19][20][21][22][23][24][25]. Many ferrocenyl compounds display interesting cytotoxic, anti-tumor, antimalarial, antifungal and DNA-cleaving activities [26][27][28].…”