Pyridocoumarin, aristolactam and aporphine alkaloids from the Australian rainforest plant Goniothalamus australis

Levrier, Claire; Balastrier, Melodie; Beattie, Karren D.; Carroll, Anthony Richard; Martin, Franklin H.; Choomuenwai, Vanida; Davis, Rohan A.

doi:10.1016/j.phytochem.2012.09.019

Cited by 72 publications

(46 citation statements)

References 39 publications

(39 reference statements)

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“…and, at the time of the present study, consisted of 260 distinct small molecules. The majority of the library compounds (;55%) have been purified from Australian natural sources, such as fungi (38), marine invertebrates (39), and plants (40). Approximately 30% of this library contained semisynthetic natural product analogs (41), whereas ;15% were known commercial drugs or synthetic compounds that were inspired by natural products.…”

Section: Screening Of the Compounds On H Contortus Larvae In Vitromentioning

confidence: 99%

Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain

et al. 2017

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As a result of limited classes of anthelmintics and an over-reliance on chemical control, there is a great need to discover new compounds to combat drug resistance in parasitic nematodes. Here, we show that deguelin, a plant-derived rotenoid, selectively and potently inhibits the motility and development of nematodes, which supports its potential as a lead candidate for drug development. Furthermore, we demonstrate that deguelin treatment significantly increases gene transcription that is associated with energy metabolism, particularly oxidative phosphorylation and mitoribosomal protein production before inhibiting motility. Mitochondrial tracking confirmed enhanced oxidative phosphorylation. In accordance, real-time measurements of oxidative phosphorylation in response to deguelin treatment demonstrated an immediate decrease in oxygen consumption in both parasitic () and free-living () nematodes. Consequently, we hypothesize that deguelin is exerting its toxic effect on nematodes as a modulator of oxidative phosphorylation. This study highlights the dynamic biologic response of multicellular organisms to deguelin perturbation.-Preston, S., Korhonen, P. K., Mouchiroud, L., Cornaglia, M., McGee, S. L., Young, N. D., Davis, R. A., Crawford, S., Nowell, C., Ansell, B. R. E., Fisher, G. M., Andrews, K. T., Chang, B. C. H., Gijs, M. A. M., Sternberg, P. W., Auwerx, J., Baell, J., Hofmann, A., Jabbar, A., Gasser, R. B. Deguelin exerts potent nematocidal activity the mitochondrial respiratory chain.

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Section: Screening Of the Compounds On H Contortus Larvae In Vitromentioning

confidence: 99%

Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain

et al. 2017

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“…[32] Anonaine has also shown antiplasmodial activity against the sensitive chloroquine (3D7) strain P. falciparum (IC 50 values of 7 AE 2 lM, equal 1.85 lg/ml) by the in-vitro [ 3 H]-hypoxanthine radiometric method. [33] On the other hand, the IC 50 23.2 AE 2.7 lg/ml for anonaine presently reported is higher than that one determined for the resistant strain Dd2 what might be related to differences in their resistance. Furthermore, anonaine disclosed a moderate cytotoxicity to HepG2 cells (CC 50 38.3 AE 2.3 lg/ml) and a low SI (1.6).…”

Section: Identification Of the Alkaloids Isolatedmentioning

confidence: 63%

“…Anonaine was assayed in vitro by the p LDH method against the sensitive (D10) and resistant chloroquine (Dd2) strains of P. falciparum and was shown to be highly active disclosing low IC 50 values (1.2 ± 0.1 μg/ml and IC 50 5.2 ± 0.3 μg/ml, respectively), in addition to CC 50 > 100 μg/ml in Chinese hamster ovarian (CHO) cells by the MTT assay . Anonaine has also shown antiplasmodial activity against the sensitive chloroquine (3D7) strain P. falciparum (IC 50 values of 7 ± 2 μ m , equal 1.85 μg/ml) by the in‐vitro [ 3 H]‐hypoxanthine radiometric method . On the other hand, the IC 50 23.2 ± 2.7 μg/ml for anonaine presently reported is higher than that one determined for the resistant strain Dd2 what might be related to differences in their resistance.…”

Section: Resultsmentioning

confidence: 99%

Antiplasmodial activity and cytotoxicity, isolation of active alkaloids, and dereplication of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS

Gontijo

Brandão

Nascimento

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives To assess the antiplasmodial activity of the ethanol extract of Xylopia sericea leaves, Annonaceae, often associated with antimalarial use and to perform a bioguided isolation of active compounds. Methods Dereplication of ethanol extract by the UPLC‐DAD‐ESI‐MS/MS technique allowed the identification of the major constituents, isolation and identification of alkaloids. The antiplasmodial and cytotoxic activity of the extract, fractions and isolated compounds was evaluated against the chloroquine‐resistant W2 strain Plasmodium falciparum and HepG2 cells, respectively. Key findings Ethanol extract showed high reduction of parasitemia as well as moderate cytotoxicity (86.5 ± 3.0% growth inhibition at 50 μg/ml and CC50 72.1 ± 5.1 μg/ml, respectively). A total of eight flavonoids were identified, and two aporphine alkaloids, anonaine and O‐methylmoschatoline, were isolated. Anonaine disclosed significant antiplasmodial effect and moderate cytotoxicity (IC50 23.2 ± 2.7 μg/ml, CC50 38.3 ± 2.3 μg/ml, SI 1.6) while O‐methylmoschatoline was not active against P. falciparum and showed a low cytotoxicity (33.5 ± 1.9% growth inhibition at 50 μg/ml, CC50 274.4 ± 0.5 μg/ml). Conclusions Characterization of Xylopia sericea leaves ethanol extract by UPLC‐DAD‐ESI‐MS/MS as well as its antiplasmodial activity and the occurrence of anonaine and O‐methylmoschatoline in this Xylopia species are reported by the first time.

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“…Briefly, the NPs in this collection have been isolated from endophytic fungi, [31] macrofungi, [32] plants, [33], and marine invertebrates (e.g., sponges [34] and ascidians [35]) with quantities ranging from 0.4 mg to >1 g. Approximately 15% of this library contains semisynthetic NP analogues, [32, 36] while a small percentage (~5%) of the library is known commercial drugs or synthetic compounds inspired by NPs. A substructure search on this NP-based library against the spermidine fragment identified five secondary metabolites as hits.…”

Section: Resultsmentioning

confidence: 99%

Natural Product Polyamines That Inhibit Human Carbonic Anhydrases

Davis

Vullo

Supuran

et al. 2014

BioMed Research International

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Natural product compound collections have proven an effective way to access chemical diversity and recent findings have identified phenolic, coumarin, and polyamine natural products as atypical chemotypes that inhibit carbonic anhydrases (CAs). CA enzymes are implicated as targets of variable drug therapeutic classes and the discovery of selective, drug-like CA inhibitors is essential. Just two natural product polyamines, spermine and spermidine, have until now been investigated as CA inhibitors. In this study, five more complex natural product polyamines 1–5, derived from either marine sponge or fungi, were considered for inhibition of six different human CA isozymes of interest in therapeutic drug development. All compounds share a simple polyamine core fragment, either spermine or spermidine, yet display substantially different structure activity relationships for CA inhibition. Notably, polyamines 1–5 were submicromolar inhibitors of the cancer drug target CA IX, this is more potent than either spermine or spermidine.

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Pyridocoumarin, aristolactam and aporphine alkaloids from the Australian rainforest plant Goniothalamus australis

Cited by 72 publications

References 39 publications

Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain

Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain

Antiplasmodial activity and cytotoxicity, isolation of active alkaloids, and dereplication of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS

Natural Product Polyamines That Inhibit Human Carbonic Anhydrases

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