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

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

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 perennial species of flowering plant in the family Apocynaceae. It is native and en ...

'' (

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 an Old World genus of flowering plants in the family Apocynaceae, The English name periwinkle is shared with the related genus '' Catharanthus'' (and with the mollusc '' Littorina littorea'') ...

'' plants. They block beta-tubulin 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 unkn ...

and

vindoline Vindoline is a chemical precursor to vinblastine. Vindoline is formed through biosynthesis from Tabersonine. See also * Lochnericine * Dimerization of catharanthine and vindoline Catharanthine and vindoline are terpenoid indole alkaloids ...

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

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

agents

vinblastine Vinblastine, 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 canc ...

and

vincristine Vincristine, also known as leurocristine and sold 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 lym ...

, 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 wit ...

chemotherapeutic agent

vinorelbine Vinorelbine, 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 mout ...

is used in the treatment of

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

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 specialize ...

in a highly

chemoselective Chemoselectivity is the preferential reaction of a chemical reagent with one of two or more different functional groups. In a chemoselective system, a reagent in the presence of an aldehyde and an ester would mostly target the aldehyde, even if it ...

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

trifluoroacetic acid Trifluoroacetic acid (TFA) is a synthetic organofluorine compound with the chemical formula CF3CO2H. It belongs to the subclass of per- and polyfluoroalkyl substances (PFASs) known as ultrashort-chain perfluoroalkyl acids (PFAAs). TFA is not ...

followed by

silver tetrafluoroborate Silver tetrafluoroborate is an inorganic compound with the molecular formula AgBF4. It is a white solid, although commercial samples often are gray, that dissolves in polar organic solvents as well as water. Preparation Silver tetrafluoroborate ca ...

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 sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...

–specific

cytotoxic drugs Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) in a standard regimen. Chemotherapy may be given with a curat ...

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 ar ...

. 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 app ...

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 Vincaminol (C20H26N2O2) is a chemical that is a part of the ''Vinca'' alkaloid group, which were discovered in the 1950s and are derived from '' Vinca minor'' (periwinkle). Vincaminol is not as well known as some of the other ''Vinca'' alkaloids ...

, vineridine, and vinburnine.

Vinpocetine Vinpocetine (ethyl apovincaminate), sold under the brand name Cavinton among others, is a synthetic derivative (chemistry), derivative of the vinca alkaloid vincamine, differing by the removal of a hydroxyl group and by being the ethyl rather th ...

is a semi-synthetic

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

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 ...

(sometimes described as "a

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

ethyl ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distinct ...

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

References

{{Reflist

External links

Chemotherapeutic ''vinca'' alkaloids
Mitotic inhibitors Plant toxins