Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Mar Drugs
2020 Dec 29;191:. doi: 10.3390/md19010011.
Show Gene links
Show Anatomy links
A Cytotoxic Porphyrin from North Pacific Brittle Star Ophiura sarsii.
Klimenko A
,
Huber R
,
Marcourt L
,
Chardonnens E
,
Koval A
,
Khotimchenko YS
,
Ferreira Queiroz E
,
Wolfender JL
,
Katanaev VL
.
???displayArticle.abstract???
Triple-negative breast cancer (TNBC) represents the deadliest form of gynecological tumors currently lacking targeted therapies. The ethanol extract of the North Pacific brittle star Ophiura sarsii presented promising anti-TNBC activities. After elimination of the inert material, the active extract was submitted to a bioguided isolation approach using high-resolution semipreparative HPLC-UV, resulting in one-step isolation of an unusual porphyrin derivative possessing strong cytotoxic activity. HRMS and 2D NMR resulted in the structure elucidation of the compound as (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid. Never identified before in Ophiuroidea, porphyrins have found broad applications as photosensitizers in the anticancer photodynamic therapy. The simple isolation of a cytotoxic porphyrin from an abundant brittle star species we describe here may pave the way for novel natural-based developments of targeted anti-cancer therapies.
19-515-55013 Russian Foundation for Basic Research, 13.1902.21.0012 Ministry of Science and Higher Education of Russia, 316030_164095 Swiss National Science Foundation
Figure 1. Extracts of Ophiura sarsii reveal anti-Wnt and cytotoxic activities. (A,B) Chromatograms of ethanol extracts of O. sarsii after additional solid-phase extraction (SPE) with elution with water (A) and methanol (B). Polar compounds, most probably inorganic salts, are abundant in the water fraction (A), while the methanol fraction (B) appears enriched in secondary metabolites of interest. (C,D) Acute cytotoxicity (CMV-Renilla) and anti-Wnt (TopFlash) biological assays reveal that the methanol fraction (D) is indeed enriched in both activities. (E) Scheme of the liquid–liquid extraction of the methanol fraction, which produced the butanol phase where the biological activities concentrated.
Figure 2. Isolation of the cytotoxic activity from O. sarsii. (A) Gradient transfer from the analytical HPLC-PDA (up) to the semipreparative HPLC-UV (down) of the butanol phase, resulted in the isolation of fraction 14. (B) NMR tubes of the different fractions, showing the strong dark-blue coloration of fraction 14. (C) Fraction 14 mediated the cytotoxic activity of O. sarsii in the acute cytotoxicity (CMV-Renilla) assay.
Figure 3. A porphyrin compound, (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid, mediates cytotoxicity of O. sarsii. (A) UV spectrum of the fraction 14 reveals absorbance peaks typical for porphyrins. (B) NMR identified the compound in fraction 14 as (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (1); ROESY correlations of compound 1 are shown as blue arrows. (C) Cell proliferation (MTT) assay shows a broad cytotoxicity of compound 1 against breast cancer lines. IC50 data are shown to the right of the graph as mean ± SEM values, n = 4.
Blagodatski,
Targeting the Wnt pathways for therapies.
2014, Pubmed
Blagodatski,
Targeting the Wnt pathways for therapies.
2014,
Pubmed
Blagodatski,
High-throughput targeted screening in triple-negative breast cancer cells identifies Wnt-inhibiting activities in Pacific brittle stars.
2017,
Pubmed
,
Echinobase
Calestani,
These Colors Don't Run: Regulation of Pigment-Biosynthesis in Echinoderms.
2018,
Pubmed
,
Echinobase
Chansakaow,
Isolation of pyropheophorbide a from the leaves of Atalantia monophylla (ROXB.) CORR. (Rutaceae) as a possible antiviral active principle against herpes simplex virus type 2.
1996,
Pubmed
Dougherty,
Introduction.
2010,
Pubmed
Dyer,
A noncommercial dual luciferase enzyme assay system for reporter gene analysis.
2000,
Pubmed
Guillarme,
Method transfer for fast liquid chromatography in pharmaceutical analysis: application to short columns packed with small particle. Part I: isocratic separation.
2007,
Pubmed
Hamblin,
Photodynamic Therapy for Cancer: What's Past is Prologue.
2020,
Pubmed
Katanaev,
The Anticancer Drug Discovery Potential of Marine Invertebrates from Russian Pacific.
2019,
Pubmed
Kennedy,
Porphyrins in invertebrates.
1975,
Pubmed
Koval,
Dramatic dysbalancing of the Wnt pathway in breast cancers.
2018,
Pubmed
Koval,
Anti-leprosy drug clofazimine inhibits growth of triple-negative breast cancer cells via inhibition of canonical Wnt signaling.
2014,
Pubmed
Koval,
Wnt3a stimulation elicits G-protein-coupled receptor properties of mammalian Frizzled proteins.
2011,
Pubmed
Li,
Clinical development and potential of photothermal and photodynamic therapies for cancer.
2020,
Pubmed
Li,
Synthesis of novel long wavelength cationic chlorins via stereoselective aldol-like condensation.
2012,
Pubmed
Miyazaki,
Purification and characterization of photosensitizing hemolytic toxin from harmful red tide phytoplankton, Heterocapsa circularisquama.
2005,
Pubmed
Nazarova,
13,15-N-cycloimide derivatives of chlorin p6 with isonicotinyl substituent are photosensitizers targeted to lysosomes.
2007,
Pubmed
Pandey,
Nature: a rich source for developing multifunctional agents. Tumor-imaging and photodynamic therapy.
2006,
Pubmed
Queiroz,
Utility of dry load injection for an efficient natural products isolation at the semi-preparative chromatographic scale.
2019,
Pubmed
Queirós,
Photodynamic therapy in dermatology: Beyond current indications.
2020,
Pubmed
Rutz,
Taxonomically Informed Scoring Enhances Confidence in Natural Products Annotation.
2019,
Pubmed
Sawa,
Targeting the Wnt signaling pathway in colorectal cancer.
2016,
Pubmed
Shaw,
Targeting the Wnt signalling pathway in cancer: prospects and perils.
2019,
Pubmed
Shaw,
A high-throughput assay pipeline for specific targeting of frizzled GPCRs in cancer.
2019,
Pubmed
Shoji,
Self-Assemblies of Zinc Bacteriochlorophyll-d Analogues Having Amide, Ester, and Urea Groups as Substituents at 17-Position and Observation of Lamellar Supramolecular Nanostructures.
2018,
Pubmed
Zhu,
Comparison between porphin, chlorin and bacteriochlorin derivatives for photodynamic therapy: Synthesis, photophysical properties, and biological activity.
2018,
Pubmed
