Rhizoxin is an

antimitotic A mitotic inhibitor, microtubule inhibitor, or tubulin inhibitor, is a drug that inhibits mitosis, or cell division, and is used in treating cancer, gout, and nail fungus. These drugs disrupt microtubules, which are structures that pull the ch ...

agent with anti-

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

activity. It is isolated from the

fungus A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

'' Rhizopus microsporus'' which causes rice seedling blight.

Biosynthesis

Rhizoxin is

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

ed by '' Paraburkholderia rhizoxinica'', a bacterial

endosymbiont An endosymbiont or endobiont is an organism that lives within the body or cells of another organism. Typically the two organisms are in a mutualism (biology), mutualistic relationship. Examples are nitrogen-fixing bacteria (called rhizobia), whi ...

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 Chemical synthesis (chemical combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In modern laboratory uses ...

, although total chemical synthesis is possible.

Cytotoxic function

Rhizoxin binds beta tubulin in

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

cells disrupting

microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nanometer, nm and have an inner diameter bet ...

formation. This, in turn, prevents formation of the

mitotic Mitosis () is a part of the cell cycle in eukaryotic cells in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis is an equational division which gives rise to genetically identical cells in which the t ...

spindle inhibiting cell division. Additionally rhizoxin can depolymerise assembled microtubules.Erratum in J. Antibiot. (Tokyo)., 40 (4), following 565. (1987) The function of rhizoxin is similar to ''Vinca'' alkaloids. Rhizoxin has undergone clinical trials as an anti-cancer drug although it did not reach later stages of

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s due to low activity ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

''. Related compounds to rhizoxin have improved biological activity (E.G Mertansine) .

Structure

Rhizoxin is a 16-membered

lactone Lactones are cyclic carboxylic esters. They are derived from the corresponding hydroxycarboxylic acids by esterification. They can be saturated or unsaturated. Lactones are formed by lactonization, the intramolecular esterification of the corresp ...

ring connected to an

oxazole Oxazole is the parent compound for a vast class of heterocyclic compound, heterocyclic aromatic organic compounds. These are azoles with an oxygen and a nitrogen separated by one carbon. Oxazoles are aromatic compounds but less so than the thiaz ...

ring by a long unsaturated chain.

References

{{reflist Oxazoles Macrolides Epoxides Polyenes Microtubule inhibitors