Short synthesis and antimalarial activity of fagaronine

Rivaud, Marion; Mendoza, Adela; Sauvain, Michel; Valentin, Alexis; Jullian, Valérie

doi:10.1016/j.bmc.2012.05.061

Cited by 25 publications

(16 citation statements)

References 26 publications

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“…Further separation yielded a very potent antiplasmodial benzophenanthridine alkaloid, fagaronine (7) with an IC 50 of 0.018 µg/mL against P. falciparum strain 3D7 (Kassim et al, 2005). A short and efficient synthesis for this compound was developed by Rivaud et al (2012), who also confirmed the compound's activity against chloroquine-sensitive and -resistant P. falciparum isolates superior to chloroquine with half maximal effective concentration (EC 50 ) of ∼10 nM in vitro and comparable to chloroquine against P. vinckei in vivo [median effective dose (ED 50 ) of 6 mg/Kg/day for 4 days]. Moreover, the compound, displayed no toxicity against Vero cells in vitro (Rivaud et al, 2012) or by single injection in the mouse at up to 50 mg/Kg (Nakanishi et al, 1999).…”

Section: Active Compounds From Nigerian Plants Alkaloidsmentioning

confidence: 99%

“…A short and efficient synthesis for this compound was developed by Rivaud et al (2012), who also confirmed the compound's activity against chloroquine-sensitive and -resistant P. falciparum isolates superior to chloroquine with half maximal effective concentration (EC 50 ) of ∼10 nM in vitro and comparable to chloroquine against P. vinckei in vivo [median effective dose (ED 50 ) of 6 mg/Kg/day for 4 days]. Moreover, the compound, displayed no toxicity against Vero cells in vitro (Rivaud et al, 2012) or by single injection in the mouse at up to 50 mg/Kg (Nakanishi et al, 1999). The methanol extract of F. zanthoxyloides also displayed >90% inhibition of Plasmodium berghei in vivo, with an estimated EC 50 of 235 mg/Kg b.w.…”

Section: Active Compounds From Nigerian Plants Alkaloidsmentioning

confidence: 99%

“…Above, we have already highlighted the ease of synthesis as one of the shortlisting criteria for progressing natural compounds down the DDP, and efforts should be initiated to establish economically viable synthesis routes for the selected candidates. To the best of our knowledge, so far only compound 7 (fagaronine) has an established chemical synthesis procedure (Rivaud et al, 2012) and funding of natural compounds synthesis research should be part of the national scientific strategy of Nigeria.…”

Section: Setting Up Synthesis Programs For the Various Compoundsmentioning

confidence: 99%

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A Review of the Antimalarial, Antitrypanosomal, and Antileishmanial Activities of Natural Compounds Isolated From Nigerian Flora

et al. 2020

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The West African country Nigeria features highly diverse vegetation and climatic conditions that range from rain forest bordering the Atlantic Ocean in the South to the Desert (Sahara) at the Northern extreme. Based on data from the World Conservation Monitoring Center of the United Nations Environmental Protection, Nigeria, with ~5,000 documented vascular plants, ranks amongst the top 50 countries in terms of biodiversity. Such a rich biodiversity implies that the country is rich in diverse secondary metabolites—natural products/unique chemicals produced by the plant kingdom to confer selective advantages to them. Like many tropical countries, Nigeria is also endemic to numerous infectious diseases particularly those caused by parasitic pathogens. These phytochemicals have been exploited for the treatment of diseases and as a result, a new branch of chemistry, natural product chemistry, has evolved, to try to reproduce and improve the therapeutic qualities of particular phytochemicals. In this review, we have compiled a compendium of natural products, isolated from Nigerian flora, that have been reported to be effective against certain protozoan parasites with the aim that it will stimulate interests for further investigations, and give impetus to the development of the natural products into registered drugs. In total 93 structurally characterized natural compounds have been identified with various levels of anti-parasite activity mainly from Nigerian plants. The synthesis protocol and molecular target for some of these natural anti-parasite agents have been established. For instance, the anti-plasmodial compound fagaronine (7), a benzophenanthridine alkaloid from Fagara zanthoxyloides has been successfully synthesized in the laboratory, and the anti-trypanosomal compound azaanthraquinone (55) elicits its effect by inhibiting mitochondrial electron transfer in trypanosomes. This review also discusses the barriers to developing approved drugs from phytochemicals, and the steps that should be taken in order to accelerate the development of new antiparasitics from the highlighted compounds.

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Section: Active Compounds From Nigerian Plants Alkaloidsmentioning

confidence: 99%

Section: Active Compounds From Nigerian Plants Alkaloidsmentioning

confidence: 99%

Section: Setting Up Synthesis Programs For the Various Compoundsmentioning

confidence: 99%

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A Review of the Antimalarial, Antitrypanosomal, and Antileishmanial Activities of Natural Compounds Isolated From Nigerian Flora

et al. 2020

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“…Their identities were established by comparison with samples previously isolated in the laboratory [10] and comparison with published spectroscopic data [25][26][27]. Fagaronine iodide (3), nornitidine (6), and norfagaronine (7) were synthetized as previously described [12]. The purity of the compounds was checked by 1 H NMR.…”

Section: Synthesis and Isolation Of Compoundsmentioning

confidence: 99%

“…We have reported the traditional use of Z. rhoifolium bark in French Guyana against malaria, and characterized the antiplasmodial activity of avicine (1), nitidine (2), and fagaridine (4) present in the traditional preparations [10]. We also described the in vivo antimalarial activity of nitidine and fagaronine [11,12]. In our continuing studies of the antileishmanial properties of natural products [13], we present here the evaluation of seven benzo[c]phenanthridines isolated from Z. rhoifolium or of synthetic origin (l " Fig.…”

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confidence: 96%

In Vitro and In Vivo Activity of Benzo[c]phenanthridines against Leishmania amazonensis

Castillo

Sauvain²,

Rivaud

et al. 2014

Planta Med

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Seven benzo[c]phenanthridines, synthetic or isolated from Zanthoxylum rhoifolium root bark, were evaluated against Leishmania amazonensis axenic amastigotes. Five of them were considered leishmanicidal, with IC50 values ranging from 0.03 to 0.54 µM, and were evaluated on intramacrophagic amastigotes of L. amazonensis. Chelerythrine displayed the best activity (IC50=0.5 µM), which was in the same range as the reference compound amphotericin B (IC50=0.4 µM). In vivo studies with chelerythrine, avicine, and fagaridine on a model of mice cutaneous leishmaniasis resulted in the identification of fagaridine as the most active compound. Fagaridine decreased the parasitic burden more than 50% at the 3rd and 6th weeks after the end of treatment.

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One‐pot Cascade Reaction for the Synthesis of Phenanthridines via Suzuki Coupling/C−H Oxidation/Aromatization

et al. 2020

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Short synthesis and antimalarial activity of fagaronine

Cited by 25 publications

References 26 publications

A Review of the Antimalarial, Antitrypanosomal, and Antileishmanial Activities of Natural Compounds Isolated From Nigerian Flora

A Review of the Antimalarial, Antitrypanosomal, and Antileishmanial Activities of Natural Compounds Isolated From Nigerian Flora

In Vitro and In Vivo Activity of Benzo[c]phenanthridines against Leishmania amazonensis

One‐pot Cascade Reaction for the Synthesis of Phenanthridines via Suzuki Coupling/C−H Oxidation/Aromatization

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