''Vinca'' alkaloids are a set of anti-mitotic and anti-microtubule

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

agents originally derived from the periwinkle plant ''

Catharanthus roseus ''Catharanthus roseus'', commonly known as bright eyes, Cape periwinkle, graveyard plant, Madagascar periwinkle, old maid, pink periwinkle, rose periwinkle, is a species of flowering plant in the family Apocynaceae. It is native and endemic to M ...

'' (

basionym In the scientific name of organisms, basionym or basyonym means the original name on which a new name is based; the author citation of the new name should include the authors of the basionym in parentheses. The term "basionym" is used in both botan ...

''Vinca rosea'') and other ''

vinca ''Vinca'' (; Latin: ''vincire'' "to bind, fetter") is a genus of flowering plants in the family Apocynaceae, native to Europe, northwest Africa and southwest Asia. The English name periwinkle is shared with the related genus ''Catharanthus'' (an ...

'' plants. They block

beta-tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...

polymerization in a dividing cell.

Sources

The Madagascan periwinkle ''

'' L. is the source for a number of important natural products, including

catharanthine Catharanthine is a terpene indole alkaloid produced by the medicinal plant ''Catharanthus roseus'' and '' Tabernaemontana divaricata''. Catharanthine is derived from strictosidine, but the exact mechanism by which this happens is currently unknow ...

and

vindoline Vindoline is a chemical precursor to vinblastine. Vindoline is formed through biosynthesis from Tabersonine Tabersonine is a terpene indole alkaloid found in the medicinal plant ''Catharanthus roseus'' and also in the genus Voacanga (both taxa b ...

and the vinca alkaloids it produces from them: leurosine and the

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

agents

vinblastine Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small cell lung cancer, bladder ca ...

and

vincristine Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's ...

, all of which can be obtained from the plant. The newer

semi-synthetic Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...

chemotherapeutic agent

vinorelbine Vinorelbine (NVB), sold under the brand name Navelbine among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer and non-small cell lung cancer. It is given by injection into a vein or by mou ...

is used in the treatment of

non-small-cell lung cancer Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to sm ...

and is not known to occur naturally. However, it can be prepared either from vindoline and catharanthine or from leurosine, in both cases by synthesis of anhydrovinblastine, which "can be considered as the key intermediate for the synthesis of vinorelbine." The leurosine pathway uses the

Nugent–RajanBabu reagent Bis(cyclopentadienyl)titanium(III) chloride, also known as the Nugent–RajanBabu reagent, is the organotitanium compound which exists as a dimer with the formula C5H5)2TiClsub>2. It is an air sensitive green solid. The complex finds specializ ...

in a highly

chemoselective Chemoselectivity is the preferential outcome of a chemical reaction over a set of possible alternative reactions. In another definition, chemoselectivity refers to the selective reactivity of one functional group in the presence of others; often ...

de-oxygenation of leurosine. Anhydrovinblastine is then reacted sequentially with ''N''-bromosuccinimide and

trifluoroacetic acid Trifluoroacetic acid (TFA) is an organofluorine compound with the chemical formula CF3CO2H. It is a structural analogue of acetic acid with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms and is a colorless liquid with ...

followed by

silver tetrafluoroborate Silver tetrafluoroborate is an inorganic compound with the chemical formula AgBF4. It is a white solid that dissolves in polar organic solvents as well as water. In its solid state, the Ag+ centers are bound to fluoride. Preparation Silver tetraf ...

to yield vinorelbine. Vinorelbine from leurosine and from catharanthine plus vindoline

Applications

''Vinca'' alkaloids are used in

for cancer. They are a class of

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

–specific

cytotoxic drugs Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

that work by inhibiting the ability of cancer cells to divide: Acting upon tubulin, they prevent it from forming into

microtubules 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 nm and have an inner diameter between 11 an ...

, a necessary component for

cellular division Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there are ...

. The ''vinca'' alkaloids thus prevent microtubule ''polymerization'', as opposed to the mechanism of action of

taxane Taxanes are a class of diterpenes. They were originally identified from plants of the genus ''Taxus'' (yews), and feature a taxadiene core. Paclitaxel (Taxol) and docetaxel (Taxotere) are widely used as chemotherapy agents. Cabazitaxel was FDA ap ...

s. ''Vinca'' alkaloids are now produced synthetically and used as drugs in cancer therapy and as immunosuppressive drugs. These compounds include vinblastine, vincristine,

vindesine Vindesine, also termed Eldisine, is a semisynthetic vinca alkaloid derived from the flowering plant ''Catharanthus roseus.'' Like the natural (e.g. vinblastine and vincristine) and semisynthetic vinca alkaloids (e.g. vinorelbine and vinflunine) ...

, and vinorelbine. Additional researched ''vinca'' alkaloids include vincaminol, vineridine, and vinburnine.

Vinpocetine Vinpocetine (ethyl apovincaminate) is a synthetic derivative of the vinca alkaloid vincamine, differing by the removal of a hydroxyl group. Vincamine is extracted from either the seeds of '' Voacanga africana'' or the leaves of ''Vinca minor'' ( ...

is a semi-synthetic

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. F ...

vincamine Vincamine is a monoterpenoid indole alkaloid found in the leaves of ''Vinca minor'' (lesser periwinkle), comprising about 25-65% of its indole alkaloids by weight. It can also be synthesized from related alkaloids. Uses Vincamine is sold in Eur ...

(sometimes described as "a synthetic

ethyl ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are ...

of apovincamine"). Minor ''vinca'' alkaloids include minovincine, methoxyminovincine, minovincinine, vincadifformine, desoxyvincaminol, and vincamajine.

References

{{Reflist

External links

Chemotherapeutic ''vinca'' alkaloids
Mitotic inhibitors Plant toxins