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Rhizoxin

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Rhizoxin
Identifiers
CAS Number
3D model (JSmol)
PubChem CID
CompTox Dashboard (EPA)
SMILES
  • O=C1C(C32O3)()C((C)/C=C/(O4)4(C)(O)C((C)(OC)/C(C)=C/C=C/C(C)=C/C5=COC(C)=N5)()OC2=O)()O1
Properties
Chemical formula C35H47NO9
Molar mass 625.749 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references
Chemical compound

Rhizoxin is an antimitotic agent with anti-tumor activity. It is isolated from a pathogenic plant fungus (Rhizopus microsporus) which causes rice seedling blight.

Biosynthesis

Rhizoxin is biosynthesised by Burkholderia rhizoxinica, a bacterial endosymbiont of the fungus Rhizopus microsporus. It is one of a large group of rhizoxin-like compounds produced by the bacteria. The bacterial endosymbiont can be grown independently in culture. This may allow easy harvesting of rhizoxin and the related compounds avoiding total chemical synthesis, although total chemical synthesis is possible.

Cytotoxic function

Rhizoxin binds beta tubulin in eukaryotic cells disrupting microtubule formation. This, in turn, prevents formation of the mitotic spindle inhibiting cell division. Additionally rhizoxin can depolymerise assembled microtubules. The function of rhizoxin is similar to Vinca alkaloids.

Rhizoxin has undergone clinical trials as an anti-cancer drug although, unfortunately, did not reach later stages of clinical trials due to low activity in vivo. Related compounds to rhizoxin may have improved biological activity.

Structure

Rhizoxin is a 16-membered lactone ring connected to an oxazole ring by a long unsaturated chain.

References

  1. Tsuro, T.; et al. (1986). "Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine resistant sublines". Cancer Res. 46 (1): 381–385. PMID 3753552. {{cite journal}}: Explicit use of et al. in: |author= (help)
  2. Ikubo, S.; et al. "In vitro evaluation of antimicrotubule agents in human small-cell lung cancer cell lines". Anticancer Res. 19: 3985–3988 year = 1999. PMID 10628341. {{cite journal}}: Explicit use of et al. in: |author= (help); Missing pipe in: |pages= (help)CS1 maint: extra punctuation (link)
  3. Laila, P. & Hertweck, C. (2005). "Pathogenic fungus harbours endosymbiotic bacteria for toxin production". Nature. 437 (7060): 884–888. doi:10.1038/nature03997. PMID 16208371.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Scherlach, K., Partida-Martinez, L.P., Dahse, H.M. & Hertweck, C. (2006). "Antimitotic Rhizoxin Derivatives from a Cultured Bacterial Endosymbiont of the Rice Pathogenic Fungus Rhizopus microsporus". J. Am. Chem. Soc. 128 (35): 11529–11536. doi:10.1021/ja062953o. PMID 16939276.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. Mitchell, I.S.; et al. (2005). "A total synthesis of the antitumour macrolide rhizoxin D". Org. Biomol. Chem. 24 (24): 4412–31. doi:10.1039/b507570j. PMID 16327903. {{cite journal}}: Explicit use of et al. in: |author= (help)
  6. Takahashi, M.; et al. (1987). "Studies on macrocyclic lactone antibiotics. XI. Anti-mitotic and anti-tubulin activity of new antitumor antibiotics, rhizoxin and its homologues". J. Antibiot. 40 (1): 66–72. PMID 3606749. {{cite journal}}: Explicit use of et al. in: |author= (help) Erratum in J. Antibiot. (Tokyo)., 40 (4), following 565. (1987).
  7. McLeod, H.L.; et al. (1996). "Multicentre phase II pharmacological evaluation of rhizoxin. Eortc early clinical studies (ECSG)/pharmacology and molecular mechanisms (PAMM) groups". Br. J. Cancer. 74 (12): 1944–8. PMC 2074819. PMID 8980394. {{cite journal}}: Explicit use of et al. in: |author= (help)
  8. Iwasaki, S.; et al. (1984). "Studies on macrocyclic lactone antibiotics. VII. Structure of a phytotoxin "rhizoxin" produced by Rhizopus chinensis". J. Antibiot. (Tokyo). 37 (4): 354–62. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: extra punctuation (link)
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