Structure‐Activity Relationships Study of Bastadin 6, an Anti‐Angiogenic Brominated‐Tyrosine Derived Metabolite from Marine Sponge

Kotoku, Naoyuki; Hiramatsu, Atsushi; Tsujita, Hiroaki; Hirakawa, Yoichi; Sanagawa, Mami; Aoki, Shunji; Kobayashi, Mariko

doi:10.1002/ardp.200700231

Cited by 20 publications

(11 citation statements)

References 20 publications

(15 reference statements)

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“…Guided by the fact that several naturally occurring bastadins are reported to exhibit anti-angiogenic effects [18,19,20,21], we evaluated if DBHB ( 8 ) also exhibits anti-angiogenic effects. Treatment of two human umbilical vein endothelial cell (HUVEC) lines, i.e.…”

Section: Resultsmentioning

confidence: 99%

“…Several reports have described the cytotoxic activity of various bastadins towards cancer cells [16,17], as well as their anti-angiogenic activity [18,19,20]. While their pro-apoptotic effects have been demonstrated in endothelial cells with respect to their cytotoxic activity [21], the mechanisms of action through which bastadins delay cancer cell growth have not yet been elucidated, to the best of our knowledge.…”

Section: Introductionmentioning

confidence: 99%

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Cyclic versus Hemi-Bastadins. Pleiotropic Anti-Cancer Effects: from Apoptosis to Anti-Angiogenic and Anti-Migratory Effects

et al. 2013

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Bastadins-6, -9 and -16 isolated from the marine sponge Ianthella basta displayed in vitro cytostatic and/or cytotoxic effects in six human and mouse cancer cell lines. The in vitro growth inhibitory effects of these bastadins were similar in cancer cell lines sensitive to pro-apoptotic stimuli versus cancer cell lines displaying various levels of resistance to pro-apoptotic stimuli. While about ten times less toxic than the natural cyclic bastadins, the synthetically derived 5,5'-dibromohemibastadin-1 (DBHB) displayed not only in vitro growth inhibitory activity in cancer cells but also anti-angiogenic properties. At a concentration of one tenth of its in vitro growth inhibitory concentration, DBHB displayed actual antimigratory effects in mouse B16F10 melanoma cells without any sign of cytotoxicity and/or growth inhibition. The serum concentration used in the cell culture media markedly influenced the DBHB-induced antimigratory effects in the B16F10 melanoma cell population. We are currently developing a specific inhalation formulation OPEN ACCESSMolecules 2013, 18 3544 for DBHB enabling this compound to avoid plasmatic albumin binding through its direct delivery to the lungs to combat primary as well as secondary (metastases) tumors.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cyclic versus Hemi-Bastadins. Pleiotropic Anti-Cancer Effects: from Apoptosis to Anti-Angiogenic and Anti-Migratory Effects

et al. 2013

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“…Mechanistically, the authors hypothesized an interaction of bastadin-6 with RyR-3, which may result in a mobilization of intracellular Ca 2+ and therefore trigger apoptosis. In a continuative study with synthetic analogues of bastadin-6 Kotoku et al [106] pointed to the oxime function and to the bromination of the aromatic rings as key structural elements with regard to the anti-proliferative effects of bastadin derivatives against HUVECs and KB3-1 cells. Derivatives where the oxime was masked lacked activity suggesting this moiety to be essential for the formation of hydrogen bond(s) with its target protein and therefore for its anti-angiogenic activity.…”

Section: Bastadins -Antifouling Agents Regulators Of Cellular Ca 2+hmentioning

confidence: 99%

Sponge Derived Bromotyrosines: Structural Diversity through Natural Combinatorial Chemistry

Niemann

Marmann

Lin

et al. 2015

Natural Product Communications

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Sponge derived bromotyrosines are a multifaceted class of marine bioactive compounds that are important for the chemical defense of sponges but also for drug discovery programs as well as for technical applications in the field of antifouling constituents. These compounds, which are mainly accumulated by Verongid sponges, exhibit a diverse range of bioactivities including antibiotic, cytotoxic and antifouling effects. In spite of the simple biogenetic building blocks, which consist only of brominated tyrosine and tyramine units, an impressive diversity of different compounds is obtained through different linkages between these precursors and through structural modifications of the side chains and/or aromatic rings resembling strategies that are known from combinatorial chemistry. As examples for bioactive, structurally divergent bromotyrosines psammaplin A, Aplysina alkaloids featuring aerothionin, aeroplysinin-1 and the dienone, and the bastadins, including the synthetically derived hemibastadin congeners, have been selected for this review. Whereas all of these natural products are believed to be involved in the chemical defense of sponges, some of them may also be of particular relevance to drug discovery due to their interaction with specific molecular targets in eukaryotic cells. These targets involve important enzymes and receptors, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), which are inhibited by psammaplin A, as well as ryanodine receptors that are targeted by bastadine type compounds. The hemibastadins such as the synthetically derived dibromohemibastadin are of particular interest due to their antifouling activity. For the latter, a phenoloxidase which catalyzes the bioglue formation needed for firm attachment of fouling organisms to a given substrate was identified as a molecular target. The Aplysina alkaloids finally provide a vivid example for dynamic wound induced bioconversions of natural products that generate highly efficient chemical weapons precisely when and where needed.

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“…Ianthella basta contains brominated macrocyclic alkaloids, so-called bastadins. Bastadins represent a unique class of natural products based on tyrosine-derived dipeptides (Kazlauskas et al, 1980, 1981; Pordesimo and Schmitz, 1990; Greve et al, 2008) with interesting medicinal properties (Franklin et al, 1996; Aoki et al, 2006; Kotoku et al, 2008). For example, they are cytotoxic against cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Chitin-based scaffolds are an integral part of the skeleton of the marine demosponge Ianthella basta

Brunner

Ehrlich

Schupp

et al. 2009

Journal of Structural Biology

160

136

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The skeletons of demosponges, such as Ianthella basta, are known to be a composite material containing organic constituents. Here, we show that a filigree chitin-based scaffold is an integral component of the I. basta skeleton. These chitin-based scaffolds can be isolated from the sponge skeletons using an isolation and purification technique based on treatment with alkaline solutions. Solid-state 13 C NMR, Raman, and FT-IR spectroscopies, as well as chitinase digestion, reveal that the isolated material indeed consists of chitin. The morphology of the scaffolds has been determined by light and electron microscopy. It consists of cross-linked chitin fibers approximately 40-100 nm in diameter forming a micro-structured network. The overall shape of this network closely resembles the shape of the integer sponge skeleton. Solid-state 13 C NMR spectroscopy was used to characterize the sponge skeleton on a molecular level. The 13 C NMR signals of the chitin-based scaffolds are relatively broad, indicating a high amount of disordered chitin, possibly in the form of surfaceexposed molecules. X-ray diffraction confirms that the scaffolds isolated from I. basta consist of partially disordered and loosely packed chitin with large surfaces. The spectroscopic signature of these chitin-based scaffolds is closer to that of α-chitin than β-chitin.

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Structure‐Activity Relationships Study of Bastadin 6, an Anti‐Angiogenic Brominated‐Tyrosine Derived Metabolite from Marine Sponge

Cited by 20 publications

References 20 publications

Cyclic versus Hemi-Bastadins. Pleiotropic Anti-Cancer Effects: from Apoptosis to Anti-Angiogenic and Anti-Migratory Effects

Cyclic versus Hemi-Bastadins. Pleiotropic Anti-Cancer Effects: from Apoptosis to Anti-Angiogenic and Anti-Migratory Effects

Sponge Derived Bromotyrosines: Structural Diversity through Natural Combinatorial Chemistry

Chitin-based scaffolds are an integral part of the skeleton of the marine demosponge Ianthella basta

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