Design and Synthesis of Hydroxyferroquine Derivatives with Antimalarial and Antiviral Activities

Biot, Christophe; Daher, Wassim; Chavain, Natascha; Fandeur, Thierry; Khalife, Jamal; Dive, Daniel; Clercq, Erik De

doi:10.1021/jm0601856

Cited by 296 publications

(229 citation statements)

References 37 publications

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“…) (Keyaerts et al, 2004;Vincent et al, 2005;Biot et al, 2006). None of the other compounds evaluated were inhibitory, including two HIV PIs previously shown to inhibit SARS-CoV replication (Chu et al, 2004;Yamamoto et al, 2004).…”

Section: Experimental Designmentioning

confidence: 99%

“…Because other groups had shown in vitro efficacy (Keyaerts et al, 2004;Vincent et al, 2005;Biot et al, 2006) (Bermejo et al, 2003). It has also been shown to inhibit viruses in cell culture including herpes simplex virus, HIV, tick-borne encephalitis virus and rotavirus (Bermejo et al, 2003), and has been in clinical trials for treating certain age groups infected with hepatitis B virus, showing modest beneficial effects (Bermejo et al, 2003) (Table 1 (Bray et al, 2002) (Sainz et al, 2004;Stroher et al, 2004) IFN-α (Cinatl et al, 2003;Sainz et al, 2004;Stroher et al, 2004) and from a study by Weck et al (1982) showing that a single high dose of human IFN-α (100,000 IU) could protect mice from death due encephalomyocarditis virus infection.…”

Section: It Was Readily Apparent That Bhc Although Well-tolerated mentioning

confidence: 99%

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Evaluation of Immunomodulators, Interferons and Known in Vitro SARS-CoV Inhibitors for Inhibition of SARS-Cov Replication in BALB/c Mice

Barnard

Day

Bailey

et al. 2006

Antivir Chem Chemother

208

193

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IFN-α-n3) did not significantly reduce lung virus titres in mice. Anti-inflammatory agents, chloroquine, amodiaquin and pentoxifylline, were also inactive in vivo, suggesting that although they may be useful in ameliorating the hyperinflammatory response induced by the virus infection, they will not significantly reduce the replication of the virus, the inducer of inflammatory response. Thus, anti-inflammatory agents may only be useful in treating virus lung infections if used in combination with agents that inhibit virus replication. In summary, the data suggest that induction of IFN by mismatched dsRNA or actual treatment with exogenous IFN-α can inhibit SARS-CoV replication in the lungs of mice.

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Section: Experimental Designmentioning

confidence: 99%

Section: It Was Readily Apparent That Bhc Although Well-tolerated mentioning

confidence: 99%

Evaluation of Immunomodulators, Interferons and Known in Vitro SARS-CoV Inhibitors for Inhibition of SARS-Cov Replication in BALB/c Mice

Barnard

Day

Bailey

et al. 2006

Antivir Chem Chemother

208

193

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“…3,4 The biological activity of ferrocenyl analogues of established drugs (e.g. ferroquine 5 or ferrocifen 6 ) or ferrocene conjugates with aminoacids, peptides, DNA, and other biomolecules has been evaluated and interesting medicinal properties have been evidenced. 7 The major part of chiral ferrocenes has been designed for use in asymmetric synthesis and several ferrocenebased ligands, mainly phosphines 8 or aminoalcohols, 9 have been found effective in catalyzing different reactions with high enantioselectivity.…”

Section: Introductionmentioning

confidence: 99%

Comparative HPLC enantioseparation of ferrocenylalcohols on two cellulose‐based chiral stationary phases

2007

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The direct HPLC enantiomeric separation of several ferrocenylalcohols on the commercially available Chiralcel OD and Chiralcel OJ columns has been evaluated in normal-phase mode. Almost all the compounds were resolved on one or both chiral stationary phases (CSPs) with separation factor (alpha) ranging from 1.06 to 2.88 while the resolution (R(s)) varied from 0.63 to 12.70 In the separation of the alpha-ferrocenylalcohols 1a-e and the phenyl analogues 2a-e, which were all resolved except 1c, a similar trend in the retention behavior for the two series of alcohols was evidenced and the selectivity was roughly complementary on the two investigated CSP. For three ferrocenylacohols, chosen as model compounds, the influence of the mobile phase composition and temperature on the enantioseparation were investigated and additional information on the chiral recognition mechanism were deduced from the chromatographic behavior of their acetylderivatives.

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“…In vivo experiments performed on rodent Plasmodium species demonstrated powerful activity of the drug and a high oral bioavailability, two major qualities for selecting lead compounds for further development (6,11). In vitro susceptibility of FQ has been tested in different culture-adapted P. falciparum strains (5,11,12) and field isolates from Gabon, Africa, Senegal, Cambodia, and Thailand (1,4,9,21,22) and has proven to be effective against CQ-sensitive (CQS) and CQR strains. More recently, the ex vivo activity of FQ against chloroquine-sensitive strains of P. vivax has been demonstrated in Thailand (19).…”

mentioning

confidence: 99%

Ex Vivo Drug Susceptibility of Ferroquine against Chloroquine-Resistant Isolates of Plasmodium falciparum and P. vivax

Marfurt

Chalfein

Prayoga

et al. 2011

Antimicrob Agents Chemother

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Ferroquine (FQ; SSR97193), a ferrocene-containing 4-aminoquinoline derivate, has potent in vitro efficacy against chloroquine (CQ)-resistant Plasmodium falciparum and CQ-sensitive P. vivax. In the current study, ex vivo FQ activity was tested in multidrug-resistant P. falciparum and P. vivax field isolates using a schizont maturation assay. Although FQ showed excellent activity against CQ-sensitive and -resistant P. falciparum and P. vivax (median 50% inhibitory concentrations [IC 50 s], 9.6 nM and 18.8 nM, respectively), there was significant cross-susceptibility with the quinoline-based drugs chloroquine, amodiaquine, and piperaquine (for P. falciparum, r ‫؍‬ 0.546 to 0.700, P < 0.001; for P. vivax, r ‫؍‬ 0.677 to 0.821, P < 0.001). The observed ex vivo cross-susceptibility is likely to reflect similar mechanisms of drug uptake/efflux and modes of drug action of this drug class. However, the potent activity of FQ against resistant isolates of both P. falciparum and P. vivax highlights a promising role for FQ as a lead antimalarial against CQ-resistant Plasmodium and a useful partner drug for artemisinin-based combination therapy.

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Design and Synthesis of Hydroxyferroquine Derivatives with Antimalarial and Antiviral Activities

Cited by 296 publications

References 37 publications

Evaluation of Immunomodulators, Interferons and Known in Vitro SARS-CoV Inhibitors for Inhibition of SARS-Cov Replication in BALB/c Mice

Evaluation of Immunomodulators, Interferons and Known in Vitro SARS-CoV Inhibitors for Inhibition of SARS-Cov Replication in BALB/c Mice

Comparative HPLC enantioseparation of ferrocenylalcohols on two cellulose‐based chiral stationary phases

Ex Vivo Drug Susceptibility of Ferroquine against Chloroquine-Resistant Isolates of Plasmodium falciparum and P. vivax

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