Antimalarial Activity of Azafluorenone Alkaloids from the Australian Tree <i>Mitrephora diversifolia</i>

Mueller, Daniela; Davis, Rohan A.; Duffy, Sandra; Avery, Vicky M.; Camp, David Brian; Quinn, Ronald J.

doi:10.1021/np900247f

Cited by 79 publications

(56 citation statements)

References 12 publications

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“…However, these compounds also exhibited cytotoxicity against the cancer cell lines KB and MCF-7, with the IC50 values ranging from 13.9-34.5 μM. According to Mueller et al [32], 5-hydroxy-6-methoxyonychine (8), an alkaloid obtained from the roots of the Australian tree plant Mitrephora diversifolia, showed IC50 values of 9.9 and 11.4 μM against the 3D7 and Dd2 clones of P. falciparum, respectively.…”

Section: Annonaceaementioning

confidence: 98%

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Antimalarial Activity of Plant Metabolites

Pan¹,

Xu²,

Shi³

et al. 2018

Preprint

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Malaria, as a major global health problem, continues to affect a large number of people each year, especially those in the developing countries. Effective drug discovery is still one of the main efforts to control malaria. As natural products are still considered as a key source for discovery and development of therapeutic agents, we have evaluated more than 2,000 plant extracts against Plasmodium falciparum. As a result, we discovered dozens of plant leads that displayed antimalarial activity. Our phytochemical study of some of these plant extracts led to identification of several potent antimalarial compounds. The prior comprehensive review article entitled "Antimalarial activity of plant metabolites" by Schwikkard and Van Heerden (2002) reported structures of plant-derived compounds with antiplasmodial activity and covered literature up to the year 2000. As a continuation of this effort, the present review covers the antimalarial compounds isolated from plants, including marine plants, reported in the literatures from 2001 to the end of 2017. During the span of the last 17 years, 175 antiplasmodial compounds were discovered from plants. These active compounds are organized in our review article according to their plant families. In addition, we also include ethnobotanical information of the antimalarial plants discussed.

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Section: Annonaceaementioning

confidence: 98%

“…The plant root extracts were further analyzed and fractionated to provide subfractions, which were also active in an in vivo study. Two compounds, β-sitosterol (32) and tormentic acid (33), were identified from the subfractions (Figure 8). Both compounds showed plasmodial inhibitory activity.…”

Section: Cecropiaceae Familymentioning

confidence: 99%

Antimalarial Activity of Plant Metabolites

Pan¹,

Xu²,

Shi³

et al. 2018

Preprint

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“…Algunos de los esqueletos que se encuentran más frecuentemente son las aporfinas, las bencilisoquinoleínas, las protoberberinas y los dímeros bis-bencilisoquinoleínas (PROTAIS et al, 1992;CORTES et al, 1992;IVORRA et al, 1993;CORTES et al, 1993b;MARTÍN et al, 1993;PROTAIS et al, 1995;BERMEJO et al, 1995). Otros como las azafluorenonas (ARANGO et al, 1987;MUELLER et al, 2009) Los alcaloides isoquinoleínicos encontrados en Annonáceas, se biosintetizan a partir de dos moléculas de tirosina (p-OH-fenilalanina) y a través de la dopamina, por lo que muchos de estos compuestos, naturales y sintéticos, muestran afinidad por algunos de los receptores dopaminérgicos, implicados en desórdenes importantes del comportamiento como la esquizofrenia, enfermedad de Huntington, trastorno de hiperactividad con déficit de atención y la enfermedad de Parkinson. Precisamente, (R)-apomorfina, aporfina semisintetizada a partir de la morfina, se ha utilizado en clínica para el tratamiento de la enfermedad de Parkinson.…”

Section: Alcaloides Isoquinoleínicosunclassified

Nuevos fármacos inspirados en Annonáceas

et al. 2014

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RESUMEN -Los metabolitos secundarios activos (MSA) juegan un papel importante en el descubrimiento de nuevos medicamentos. Moléculas naturales con esqueletos complejos, tales como las estatinas aisladas de Aspergillus terreus, o las acetogeninas específicas de la familia Annonaceae, no hubieran podido ser inventadas en ningún laboratorio. Los MSA aislados en Annonaceae, especialmente las acetogeninas y los alcaloides isoquinoleínicos, pueden ser considerados como fuente constante de inspiración para químicos, farmacólogos y para todos los investigadores interesados en el descubrimiento de una nueva familia de medicamentos. Terminos para indexacion: Annonaceae, acetogeninas, antitumorales, insecticidas, alcaloides isoquinoleínicos, dopaminérgicos, antimicrobianos. NEW MEDICINES INSPIRATED IN ANNONACEASABSTRACT -Active secondary metabolites (ASM) play a highly significant role in the drug discovery. Natural complex chemical skeleton such as statins isolated from Aspergillus terreus, or acetogenins specific from Annonaceae family, are not able to be invented in any laboratory. The ASM isolated from Annonaces, especially acetogenins and isoquinoline alkaloids should be considered as a source of continuous inspiration for the chemists, the pharmacologists and all researchers that are interested in discovering a new drug family. Los metabolitos secundarios (MS) han sido la principal fuente de diversidad química que ha dirigido el descubrimiento y desarrollo de nuevos agentes terapéuticos en el siglo pasado. Muchos productos de origen natural o análogos estructurales preparados por síntesis, han sido desarrollados con éxito para combatir enfermedades humanas en prácticamente todas las áreas terapéuticas. La época posterior al descubrimiento de la penicilina, durante la segunda guerra mundial, fue la más floreciente en cuanto a los esfuerzos dedicados por las empresas farmacéuticas al descubrimiento de nuevos metabolitos secundarios activos (MSA), moléculas de origen natural con interés terapéutico, centradas principalmente en la búsqueda de antibióticos (Figura 1).Pero estos esfuerzos no se dirigieron únicamente al desarrollo de compuestos antibacterianos o antifúngicos sino que también se amplió el objetivo a otras enfermedades no infecciosas. Así en los años 70, como ejemplo, se desarrollaron la mevastatina, aislada en cultivos de Penicillium citrinum y la lovastatina aislada a partir de un extracto del hongo Aspergillus terreus, como inhibidores de la biosíntesis de colesterol en el hígado, que son la base principal del tratamiento actual de las nuevas estatinas de síntesis (BAKER et al., 2007).Sin embargo, a pesar de estos éxitos indudables la gran industria farmacéutica disminuyó el interés por la investigación en productos naturales a lo largo de los años 90 y principios de la década del 2000, para focalizar la búsqueda de nuevos compuestos activos mediante el rastreo automatizado a gran escala (high throughpout screening, HTS) aplicados a librerías de compuestos generados por la química combinatoria (NEWMAN e C...

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“…Azafluorenones represent the heterocyclic cores of many molecules of biological interest; derivatives have, for example, been described for their antifungal, 1 antibacterial, 2 and antimalarial 3 properties. In the course of the development of lithium-metal amido-based heterometallic bases, synergic reagents with which to functionalize aromatic compounds unsuitable for reaction with traditional organolithium bases have been identified and developed.…”

Section: Introductionmentioning

confidence: 99%

Efficient two-step access to azafluorenones and related compounds

Marquise

Harford

Chevallier

et al. 2013

Tetrahedron Letters

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Efficient two-step access to azafluorenones and related compounds. Tetrahedron Letters, Elsevier, 2013, 54 (24) Abstract:Crystals of a lithiocuprate prepared from copper(I) chloride and lithium 2,2,6,6-tetramethylpiperidide (2 equiv) were isolated and analysed by X-ray diffraction as (TMP)2Cu(Cl)Li2·THF. The observation of this species is consistent with its having a role in deprotocupration-aroylation for a higher-order bis(amido)cuprate. Phenyl pyridyl ketones, phenyl quinolyl ketones and phenyl thienyl ketones were prepared in tetrahydrofuran by this sequence using the lithiocuprate and aroyl chorides as electrophiles. Diaryl ketones bearing a chloro group at the 2 position (of a pyridyl or phenyl group) thus synthesized were next converted through palladium-catalysed ring closure to polycycles of the 5H-indeno

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Antimalarial Activity of Azafluorenone Alkaloids from the Australian Tree Mitrephora diversifolia

Cited by 79 publications

References 12 publications

Antimalarial Activity of Plant Metabolites

Antimalarial Activity of Plant Metabolites

Nuevos fármacos inspirados en Annonáceas

Efficient two-step access to azafluorenones and related compounds

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