Rhizoxin

From Wikipedia, the free encyclopedia

Rhizoxin
Identifiers
CAS number [90996-54-6]
PubChem 11969567
Properties
Molecular formula C35H47NO9
Molar mass 625.749 g/mol
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Rhizoxin is an antimitotic agent with anti-tumor activity.[1][2] It is isolated from a pathogenic plant fungus (Rhizopus microsporus) which causes rice seedling blight.

Contents

[edit] Biosynthesis

Rhizoxin is biosynthesised by Burkholderia rhizoxina, an endosymbiotic bacteria of the fungus Rhizopus microsporus.[3] It is one of a large group of rhizoxin-like compounds produced by the bacteria.[4] The bacterial endosymbiote 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[5].

[edit] 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.[6] The function of rhizoxin is similar to Vinca alkaloids.

Rhizoxin has undergone clinical trials as an anti-cancer drug[7] 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.[4]

[edit] Structure

Rhizoxin is a 16-member lactone ring connected to an oxazole ring by a long unsaturated chain.[8]

[edit] References

  1. ^ Tsuro, T., et al., "Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine resistant sublines". Cancer Res., 46, 381-385 (1986).
  2. ^ Ikubo, S., et al., "In vitro evaluation of antimicrotubule agents in human small-cell lung cancer cell lines". Anticancer Res., 19, 3985-3988 (1999).
  3. ^ Laila, P., et al., "Pathogenic fungus harbours endosymbiotic bacteria for toxin production"., Nature 437, 884-888., (2005).
  4. ^ a b Scherlach, K., et al., "Antimitotic Rhizoxin Derivatives from a Cultured Bacterial Endosymbiont of the Rice Pathogenic Fungus Rhizopus microsporus". J. Am. Chem. Soc. 128 (35) 11529 - 11536., (2006).
  5. ^ Mitchell, I.S., et al., "A total synthesis of the antitumour macrolide rhizoxin D". Org. Biomol. Chem. 24 4412-31 (2005).
  6. ^ Takahashi, M., et al., "Studies on macrocyclic lactone antibiotics. XI. Anti-mitotic and anti-tubulin activity of new antitumor antibiotics, rhizoxin and its homologues." J. Antibiot. (Tokyo)., 40 (1), 66-72. (1987). Erratum in J. Antibiot. (Tokyo)., 40 (4), following 565. (1987).
  7. ^ McLeod, H.L., et al., "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., (1996).
  8. ^ Iwasaki, S., et al., "Studies on macrocyclic lactone antibiotics. VII. Structure of a phytotoxin "rhizoxin" produced by Rhizopus chinensis." J. Antibiot. (Tokyo). 37 (4), 354-62 (1984).