Slayt 1

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Symposium of the Center for Marine Natural
Products and Drug Discovery on Marine Natural
Products and Drug Discovery (CMDDS 2006)
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• Takeshi Yasumoto
• Chemistry, etiology and food chain dynamics of
  marine toxins
• Junichi Kobayashi
• Bioactive products from Okinawan marine micro-
  and macroorganisms
• Tae Kook Kim
• A magnetic nanoprobe technology for detecting
  molecular interactions in live cells
• Motomasa Kobayashi
• Anti-angiogenic substances from marine sponge

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• Takeshi Yasumoto
• Chemistry, etiology and food chain dynamics of
  marine toxins

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Chemistry, etiology and food chain dynamics of
marine toxins

• Fish and shellfish, though delicious and
  considered good for ones health occasionally
  accumulate natural toxins and thereby cause food
  poisoning
• Ciguatera Fish Poisoning
• Small marine snail (Cigua) Caribbean
• Neurological and gastrointestinal syndromes
• Rare fatal cases
• High mortality rate
• 20000-60000 patients worldwide

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Chemistry, etiology and food chain dynamics of
marine toxins

• 1960 A Lipophilic toxin, Ciguatoxin (CTX) was
  isolated from moray eels
• 1977 Abundance of disk-shaped dinoflagellate
  (Gambierdiscus toxicus) in digestive content of
  C. Striatus
• Gambierdiscus toxicus contains two types of
  toxins differ on polarity
• Less polar CTX and more polar Maitotoxin (MTX)

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Chemistry, etiology and food chain dynamics of
marine toxins

• 0.35 mg pure CTX extracted from 4 tons moray eels
  collected from ciguatera-endemic areas
• 0.75 mg of a CTX analog coded CTX4B from wild G.
  toxicus
• Cultured G. toxicus produced two new
  poly-cyclic-ether toxins CTX3C and gambierol
  gambieric acid

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Chemistry, etiology and food chain dynamics of
marine toxins

• Maitotoxin (C164H256Na2O68S2) MW 3422 one of
  the larger natural product
• Lethal Dose, 50 (LD50) (mice) 50ng/kg
• Lethality is 200 times more potent than
  tetradoxin
• Tetradoxin is an extremely potent sodium channel
  blocker which if ingested, will cause muscle
  paralysis then death due to respiratory failure.
• Lethal dose for an adult is 1-2 mg

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• Junichi Kobayashi
• Bioactive products from Okinawan marine micro-
  and macroorganisms

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Bioactive products from Okinawan marine micro-
and macroorganisms

• Amphidinolides G (1) and H (2) isolated from the
  marine dinoflagellate Amphidinium sp. are potent
  cytotoxic 27- and 26-membered macrolides
• Amphidinolide H (2) exhibits antitumor activity
  against murine leukemia P388 mice (T/C140 at a
  dose of 0.2 mg/kg).

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Bioactive products from Okinawan marine micro-
and macroorganisms

• Amphidinolide X isolated from a marine
  dinoflagellate Amphidinium sp. Is the first
  macrodiolide consisting of polyketide-derived
  diacid and diol units from natural sources
• Amphidinolides X shows cytotoxicity against L1210
  (IC50 0.6) and KB cells (IC50 7.5).

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• Tae Kook Kim
• A magnetic nanoprobe technology for detecting
  molecular interactions
• in live cells

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A magnetic nanoprobe technology for detecting
molecular interactions in live cells

• Technology called magnetism-based interaction
  capture (MAGIC) that identifies molecular targets
  on the basis of induced movement of
  superparamagnetic nanoparticles inside living
  cells.
• These nanomagnetic probes was built up to develop
  a target ID technology MAGIC, to directly probe
  molecular interactions inside living cells with
  high sensitivity and selectivity
• After internalization of small moleculecoated
  MNPs into the cells, protein(s) bind to the small
  molecule on the MNP.

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A magnetic nanoprobe technology for detecting
molecular interactions in live cells

• When a magnetic field is applied, the MNP and
  associated target protein(s) can be concentrated.

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• Motomasa Kobayashi
• Anti-angiogenic substances from marine sponge

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Anti-angiogenic substances from marine sponge

• Angiogenesis is the process of generating new
  capillary blood vessels, which is responsible for
  the progression of solid tumors, diabetic
  retinopathy, psoriasis, and rheumatoid arthritis.
• Tumor growth and metastasis are highly dependent
  on angiogenesis.Therefore, specific inhibitors of
  angiogenesis are expected to be promising
  antitumor agents.

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Anti-angiogenic substances from marine sponge

• Four novel steroidal alkaloids named cortistatins
  A (1), B (2), C (3), and D (4) were isolated from
  the marine sponge Corticium simplex.

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Anti-angiogenic substances from marine sponge

• Cortistatin A (1) showed cytostatic
  anti-proliferative activity against human
  umbilical vein endothelial cells (HUVECs) at 100
  pM to 1 µM,
• Cortistatin A also inhibited migration and
  tubular formation of HUVECs