Plakortethers A−G: A New Class of Cytotoxic Plakortin−Derived Metabolites

Campagnuolo, Claudio; Fattorusso, Ernesto; Taglialatela‐Scafati, Orazio; Ianaro, Angela; Pisano, Maria Barbara

doi:10.1002/1099-0690(20021)2002:1<61::aid-ejoc61>3.0.co;2-e

Cited by 30 publications

(27 citation statements)

References 7 publications

(18 reference statements)

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“…Indeed, 2D NMR spectra revealed the presence of a single set of characteristic proton and carbon signals, e.g. those at positions 10 (δ H = 3.98, δ C = 65.2) and 9 (δ H = 3.89, δ C = 79.2), assigned by comparison with literature data1231 (Supplementary Figure S2). …”

Section: Resultsmentioning

confidence: 86%

The interaction of heme with plakortin and a synthetic endoperoxide analogue: new insights into the heme-activated antimalarial mechanism

Persico

Fattorusso

Taglialatela‐Scafati

et al. 2017

Sci Rep

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In the present work we performed a combined experimental and computational study on the interaction of the natural antimalarial endoperoxide plakortin and its synthetic analogue 4a with heme. Obtained results indicate that the studied compounds produce reactive carbon radical species after being reductively activated by heme. In particular, similarly to artemisinin, the formation of radicals prone to inter-molecular reactions should represent the key event responsible for Plasmodium death. To our knowledge this is the first experimental investigation on the reductive activation of simple antimalarial endoperoxides (1,2-dioxanes) by heme and results were compared to the ones previously obtained from the reaction with FeCl2. The obtained experimental data and the calculated molecular interaction models represent crucial tools for the rational optimization of our promising class of low-cost synthetic antimalarial endoperoxides.

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Section: Resultsmentioning

confidence: 86%

The interaction of heme with plakortin and a synthetic endoperoxide analogue: new insights into the heme-activated antimalarial mechanism

Persico

Fattorusso

Taglialatela‐Scafati

et al. 2017

Sci Rep

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“…200 Japanese specimens of Callyspongia truncata yielded the α-glucosidase inhibitor callyspongynic acid 210 201 while corticatic acids D 211 and E 212 along with the previously reported corticatic acid A, 202 were isolated from a Japanese Petrosia corticata and found to be geranylgeranyltransferase type I inhibitors. 213 Plakortone D 234, originally isolated from P. halichondrioides, 214 has been synthesised thereby establishing the relative stereochemistry of C-10 and its absolute configuration as illustrated. 204 A series of polymethoxydienes 214-218, similar to the alkenes isolated from the cyanophyte Tolypothrix conglutinata, 205 were isolated from a Philippine specimen of Myriastra clavosa, and found to be moderately cytotoxic.…”

Section: Spongesmentioning

confidence: 99%

Marine natural products

et al. 2004

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This review covers the literature published in 2002 for marine natural products, with 579 citations (413 for the period January to December 2002) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (677 for 2002), together with their relevant biological activities, source organisms and country of origin. Syntheses that lead to the revision of structures or stereochemistries have been included (114), including any first total syntheses of a marine natural product.

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“…Assays on cytotoxic activity were performed for epichromazonarol against P-388, A-549, HT-29, and MEL-28 cells, and in all cases an IC 50 = 15.9 μM was obtained for epichromazonarol [ 28 ], while Plakortether E was evaluated for cytotoxic activity against two different cell lines: WEHI 164 (murine fibrosarcoma) and RAW 264-7 (murine macrophage). Plakortether E proved to be selectively active against the second cell line [ 29 ]. Moreover, stoloniferone O, imposed significant antitumoral effects on HT-29 and P-388 cell lines [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

New Cytotoxic Cerebrosides from the Red Sea Cucumber Holothuria spinifera Supported by In-Silico Studies

et al. 2020

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Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC50 values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC50 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents.

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Plakortethers A−G: A New Class of Cytotoxic Plakortin−Derived Metabolites

Cited by 30 publications

References 7 publications

The interaction of heme with plakortin and a synthetic endoperoxide analogue: new insights into the heme-activated antimalarial mechanism

The interaction of heme with plakortin and a synthetic endoperoxide analogue: new insights into the heme-activated antimalarial mechanism

Marine natural products

New Cytotoxic Cerebrosides from the Red Sea Cucumber Holothuria spinifera Supported by In-Silico Studies

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