Rhizoxin

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Rhizoxin
Rhizoxin.png
Identifiers
CAS number 90996-54-6 YesY
PubChem 11969567
ChEMBL CHEMBL379989 N
Jmol-3D images Image 1
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 (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox 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.

Biosynthesis[edit]

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

Cytotoxic function[edit]

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]

Structure[edit]

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

References[edit]

  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. 
  2. ^ Ikubo, S., et al., (1999). "In vitro evaluation of antimicrotubule agents in human small-cell lung cancer cell lines". Anticancer Res. 19 (5B): 3985–3988. PMID 10628341. 
  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. 
  4. ^ a b 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. 
  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. 
  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. doi:10.7164/antibiotics.40.66. PMID 3606749.  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. 
  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. doi:10.7164/antibiotics.37.354.