On the Molecular Mechanisms of the Antimalarial Action of Ferroquine

Dubar, Faustine; Biot, Christophe

doi:10.1002/9783527673438.ch05

Cited by 3 publications

(3 citation statements)

References 80 publications

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“…We have already discussed its role in enhancing the efficacy and range of applicability of tamoxifen by replacing a phenyl substituent by ferrocenyl in the ferrocifens for the treatment of a broad range of cancers [63]. Another spectacular advance has been the adoption of ferroquine as a replacement for chloroquine in the world-wide fight against malaria [70]. It is evident that the electronic control exerted by the ferrocenyl group continues to attract attention, and will undoubtedly lead to additional practical applications.…”

Section: Concluding Commentsmentioning

confidence: 99%

Ferrocenyl Migrations and Molecular Rearrangements: The Significance of Electronic Charge Delocalization

McGlinchey

2020

Inorganics

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The enhanced stabilization of a carbocationic site adjacent to a ferrocenyl moiety was recognized within a few years of the discovery of sandwich compounds. While a detailed understanding of the phenomenon was the subject of some early debate, researchers soon took advantage of it to control the ease and direction of a wide range of molecular rearrangements. We, here, discuss the progress in this area from the pioneering studies of the 1960s, to more recent applications in chromatography and analytical detection techniques, and currently in the realm of bioactive organometallic complexes. Several classic reactions involving ferrocenyl migrations, such as the pinacol, Wolff, Beckmann, and Curtius, are discussed, as well as the influence of the ferrocenyl substituent on the mechanisms of the Nazarov, Meyer-Schuster, benzoin, and Stevens rearrangements. The preparation and isomerizations of ferrocenyl-stabilized vinyl cations and vinylcyclopropenes, together with the specific cyclization of acetylcyclopentadienyl-metal derivatives to form 1,3,5-substituted benzenes, demonstrate the versatility and generality of this approach.

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Section: Concluding Commentsmentioning

confidence: 99%

Ferrocenyl Migrations and Molecular Rearrangements: The Significance of Electronic Charge Delocalization

McGlinchey

2020

Inorganics

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“…The rationale behind synthesizing ferrocenyl analogs of DCQ stems from previously published studies by Jaouen, Biot, and co-workers, which showed that ferrocenyl analogs of tamoxifen and chloroquine had improved bioactivities compared to the original parent compounds. − Further studies showed that the ferrocenyl component made a difference by producing reactive oxygen species, increasing lipophilicity of the molecule, and provided additional mechanisms of action compared to that of the original drug. − At our end, we have, over the past few years, used this strategy to unveil novel lead compounds against different parasitic diseases such as schistosomiasis or fungal agents. ,,, …”

Section: Introductionmentioning

confidence: 99%

Organometallic Derivatives of Decoquinate Targeted toward Toxoplasma gondii

et al. 2022

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Toxoplasmosis is an infection contracted by exposure to Toxoplasma gondii and can have deleterious health effects on pregnant women and their children. Current treatments for the infection are complex and have considerable undesired side effects, raising the need for new treatments. Herein, we report the synthesis, characterization, and biological testing of some organometallic derivatives of the commercially available, broadspectrum antiparasitic, decoquinate (DCQ). The cyclic secondary amine of decoquinate was functionalized with a range of groups (i.e., ferrocene, ruthenocene, and phenyl) with either methyl or vinyl bridges. Through measurement of half maximal inhibitory concentrations (IC 50 ) and T. gondii proliferation assays, it was found that ferrocenylvinyl-DCQ and an oxygenalkylated phenylvinyl-DCQ side product reduced proliferation of the parasite by 84% at 1 μM, which approached that of the parent drug (96%). These data provide a possible roadmap for future investigations on the derivatization of DCQ to yield better treatments for toxoplasmosis, particularly the functionalization of the cyclic ketone.

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“…No other ferrocene analogues had equal or better anti-malarial activity despite the structure-activity investigation on another 120 ferrocenyl derivatives. After various validations of its specific pharmacology,23,24 FQ entered phase I clinical trials with Sanofi-Aventis in 2003 in Gabon, Senegal, Cambodia, Thailand and Madagascar 24. Initially, FQ was used in dual therapy with artesunate (ARS), a semi-synthetic analogue of artemisinin,25 the traditional Chinese anti-malarial drug discovered by Tu Youyou…”

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confidence: 99%