“Rhizoxin”的意思、由来-开放百科全书

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

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

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 it 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

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

References

1. ^{{cite journal | author = Tsuro, T.| title = Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine resistant sublines | journal = Cancer Res. | volume = 46 | pages = 381–385 | year = 1986 | pmid = 3753552 | issue = 1|display-authors=etal}}
2. ^{{cite journal | author = Ikubo, S., et al., | title = In vitro evaluation of antimicrotubule agents in human small-cell lung cancer cell lines | journal = Anticancer Res. | volume = 19 | pages = 3985–3988 |year = 1999 | pmid=10628341 | issue = 5B}}
3. ^{{cite journal |author1=Laila, P. |author2=Hertweck, C. |lastauthoramp=yes | title = Pathogenic fungus harbours endosymbiotic bacteria for toxin production | journal = Nature | volume = 437 | pages = 884–888 | year = 2005 | doi = 10.1038/nature03997 | pmid = 16208371 | issue = 7060}}
4. ^¹{{cite journal | author = Scherlach, K., Partida-Martinez, L.P., Dahse, H.M. & Hertweck, C. | title = Antimitotic Rhizoxin Derivatives from a Cultured Bacterial Endosymbiont of the Rice Pathogenic Fungus Rhizopus microsporus | journal = J. Am. Chem. Soc. | volume = 128 | pages = 11529–11536 | year = 2006 | doi = 10.1021/ja062953o | pmid = 16939276 | issue = 35}}
5. ^{{cite journal | author = Mitchell, I.S.| title = A total synthesis of the antitumour macrolide rhizoxin D | journal = Org. Biomol. Chem. | volume = 3 | pages = 4412–31 | year = 2005 | doi = 10.1039/b507570j | pmid = 16327903 | issue = 24|display-authors=etal}}
6. ^{{cite journal | author = Takahashi, M.| title = Studies on macrocyclic lactone antibiotics. XI. Anti-mitotic and anti-tubulin activity of new antitumor antibiotics, rhizoxin and its homologues | journal = J. Antibiot. | volume = 40 | issue = 1 | pages = 66–72 | year = 1987 | pmid = 3606749 | doi=10.7164/antibiotics.40.66|display-authors=etal}} Erratum in J. Antibiot. (Tokyo)., 40 (4), following 565. (1987).
7. ^{{cite journal | author = McLeod, H.L.| title = Multicentre phase II pharmacological evaluation of rhizoxin. Eortc early clinical studies (ECSG)/pharmacology and molecular mechanisms (PAMM) groups | journal = Br. J. Cancer | volume = 74 | issue = 12 | pages = 1944–8 | year = 1996 | pmid = 8980394 | pmc = 2074819|display-authors=etal | doi=10.1038/bjc.1996.657}}
8. ^{{cite journal | author = Iwasaki, S., et al., | title = Studies on macrocyclic lactone antibiotics. VII. Structure of a phytotoxin "rhizoxin" produced by Rhizopus chinensis | journal = J. Antibiot. (Tokyo) | volume = 37 | issue = 4 | pages = 354–62 | year = 1984 | doi=10.7164/antibiotics.37.354}}