Periwinkle plant

Vinca alkaloids (vincristine, vinblastine, vindesine) are derived from the periwinkle plant (Vinca rosea), they bind to tubulin and inhibit its polymerization into microtubules and spindle formation, thus producing metaphase arrest. They are cell cycle specific and interfere also with other cellular activities that involve microtubules, such as leukocyte phagocytosis, chemotaxis, and axonal transport in neurons. Vincristine is mainly neurotoxic and mildly hematotoxic, vinblastine is myelosuppressive with veiy low neurotoxicity whereas vindesine has both, moderate myelotoxicity and neurotoxicity. 

Vinca alkaloids are derived from the Madagascar periwinkle plant, Catharanthus roseus. The main alkaloids are vincristine, vinblastine and vindesine. Vinca alkaloids are cell-cycle-specific agents and block cells in mitosis. This cellular activity is due to their ability to bind specifically to tubulin and to block the ability of the protein to polymerize into microtubules. This prevents spindle formation in mitosing cells and causes arrest at metaphase. Vinca alkaloids also inhibit other cellular activities that involve microtubules, such as leukocyte phagocytosis and chemotaxis as well as axonal transport in neurons. Side effects of the vinca alkaloids such as their neurotoxicity may be due to disruption of these functions. 

Runguphan W, O Connor SE. (2009) Metabolic reprogramming of periwinkle plant culture. Nat Chem Biol 5 151-153. 

The discovery of vinblastine and vincristine is one of the most intriguing examples of serendipity in scientihc research in recent years. In 1952, the Canadian medical researcher Robert Laing Noble (1910-90) received a package from his brother. Dr. Clark Noble, containing 25 leaves from the Madagascar periwinkle plant. Vinca rosea. Clark had received the leaves from one of his patients in Jamaica, who said that natives on the island often used the plant to control their diabetes when insulin was not available. Clark, who was retired, suggested that his brother study the plant for possible use as a drug for the treatment of diabetes. 

The contractile proteins of the spindle apparatus must draw apart the replicated chromosomes before the cell can divide. This process is prevented by the so-called spindle poisons (see also colchicine, p. 316) that arrest mitosis at metaphase by disrupting the assembly of microtubules into spindle threads. The vinca alkaloids, vincristine and vinblastine (from the periwinkle plant. Vinca rosea) exert such a cell-cycle-specific effect. Damage to the nervous system is a predicted adverse effect arising from injury to microtubule-operated axonal transport mechanisms. 

The vinca alkaloids comprise vincristine and vinblastine. These complex, heterocyclic alkaloids are derived from the periwinkle plant. Vindesine and vi-norelbine are semisynthetic analogues. These drugs are M-phase specitic. Binding specifically to tubulin they inhibit the polymerization of microtubules. The consequent ineffective chromosome segregation initiates apoptosis for both normal and malignant cells. 

Vincristine (Oncovin) and vinblastine (Velban) are both produced by the leaves of the periwinkle plant. Despite their structural similarity, there are significant differences between them in regard to clinical usefulness and toxicity. 

Vinblastine is an alkaloid derived from the periwinkle plant Vinca rosea. Its mechanism of action involves inhibition of tubulin polymerization, which disrupts assembly of microtubules, an important part of the cytoskeleton and the mitotic spindle. This inhibitory effect results in mitotic arrest in metaphase, bringing cell division to a halt, which then leads to cell death. Vinblastine and other vinca alkaloids are metabolized by the liver P450 system, and the majority of the drug is excreted in feces via the biliary system. As such, dose modification is required in the setting of liver dysfunction. The main adverse effects are outlined in Table 54-4, and they include nausea and vomiting, bone marrow suppression, and alopecia. This agent is also a potent vesicant, and care must be taken in its administration. It has clinical activity in the treatment of Hodgkin s... 

Vincristine [vin KRIS teen] and vinblastine [vin BLAST een] are structurally-related compounds derived from the periwinkle plant, Vinca rosea. They are therefore referred to as the vinca alkaloids. A structurally related new (and less toxic) agent, vinorelbine [vye NO rel been] shows promise in the treatment of advanced non-small cell lung cancer. 

The vinca alkaloids, vincristine and vinblastine (from the periwinkle plant, Vinca rosea), inhibit the polymerization of tubulin subunits into microtubuli. Damage to the nervous system is a predicted adverse effect arising from injury to microtubule-operated axonal transport mechanisms. 

Vinblastine Sulfate, USP. Vinblastine sulfate. Vcihun. vincaleucohlastinc. VLB. NSC-49842, is an antitumor alkaloid isolated from Vim ti rosea L.. the periwinkle plant. It is soluble in water and alcohol. Vials containing 10 mg of vinblastine sulfate as a lyophili/cd plug are supplied. It is reconstituted by the addition of sodium chloride solution for injection preserved with phenol or benzyl alcohol. 

Shepardson, S., and Me Crum, R.C. (1973). Effect of gibberellic acid on mycoplasma like organism-infected and healthy periwinkle. Plant Disease Reporter, 63 865-869. 

A total synthesis of vinblastine has not as yet been achieved. Methods of preparation involve making initial crude extracts from the periwinkle plant, followed by extraction at selected pH into organic solvents, and final separation of the complex mixture of alkaloids by column chromatography. Several methods have been devised since Noble, Beer, and Cutts1 first reported the isolation of vinblastine as the sulfate salt. A few are briefly described here. 

Vinca alkaloids (vincristine, vinblastine, vinorelbine) are derived from the periwinkle plant (Vinca rosea). These agents work by binding to tubulin at a site different than colchicine or paclitaxel. They block polymerization, which prevents the formation of the mitotic spindle, and are used as antineoplastic agents. Taxanes produce a stabilization of microtubules similar to colchicine, but by a different mechanism, and also halt cells in metaphase. Paclitaxel (taxol) is the taxane used clinically. It is derived from the bark of the pacific yew. Taxol disrupts several microtubule-based functions as completely as inhibitors of polymerization, emphasizing the importance of assembly/disassembly balance in microtubule function. Recently, it has been found that paclitaxel also binds to and inhibits the function of a protein called bcl-2, an inhibitor of one or more pathways involved in mediating apoptosis. PaclitaxeTs interference with this function promotes apoptosis in addition to its microtubule-related inhibition of cell division. 

Antimicrotubule agentArinca alkaloid derived from the periwinkle plant disrupts formation of microtubules... 

First studies were undertaken with Periwinkle plants from Jamaica. The roots, stems, and leaves all contain active material the leaves contain the highest proportion of activity, but in the seeds almost no activity is found.Today we know that four of the pure alkaloids, crystallised from extracts of Vinca rosea plants, namely vinblastine [(169), = vincaleukoblastine)], vincristine [(170), = leurocristine], vinleurosine [= leurosine, (183)], and vinrosidine [= leurosidine, (181)] show good effects in suppression of tumour growth. In the last decade about fifty-five alkaloids have been found in Vinca rosea extracts and tested for their pharmacological effects. Besides the four mentioned none of the... 

Vinca alkaloids are extracted from the periwinkle plant. Vinca rosea, although newer ones are semi-synthetic. They bind to tubulin and prevent its polymerization into microtubules. Microtubules form the spindle during mitosis, so vinca alkaloids halt mitosis at a certain stage. 

The periwinkle plant (Vinca rosa), which is indigenous to Florida, has yielded several indole alkaloids. Two with antineoplastic properties are the dimeric indole-dihydroindole derivatives vinblastine (Velban ) and vincristine (Oncovin ). These agents bind to tubulin, arresting mitosis at the metaphase. 

Vinblastine is an alkaloid derived from Vinca rosea, the periwinkle plant. Its mechanism of action involves depolymerization of microtubules, which are an important part of the cytoskeleton and the mitotic spindle. The drug binds specifically to the microtubular protein tubulin in dimeric form the drug-tubulin complex joins to the forming end of... 

No bone marrow depression. Autonomic, peripheral and motor neuropathy, injection site necrosis. IV. Hepatic metabolism, biliary excretion. Acute lymphocytic leukemia, Hodgkin s lymphoma, some solid tumors. Isolated from periwinkle plant. 

The list of commercial products from natural sources could fill volumes. It must be emphasized that their discoveries range from systematic searches, to tradition to chance favors the prepared mind. The latter is reemphasized in the discovery of the alkaloids from the periwinkle plant (vincristine and vinblastine) which were first screened for their hypoglycemic activity based on reports of their use by local groups in Madagascar. While the hypoglycemic response could not be confirmed under controlled laboratory conditions, an immunosuppressive effect due to... 

Initial methods for the isolation of vinblastine from the periwinkle plants (vinca rosea) had been described (5,7,23-25) and well documented in several texts including the previous profile of vinblastine sulfate (12). Isolation of vinblastine and vincristine from Catharanthus roseus continues to receive attention, and several procedures have been reported (mainly in the patent literature) for the isolation and separation of these alkaloids (24-29). Extracts of Catharanthus roseus have been found to contain N-demethylvinblastine and this can be used to prepare vincristine by formylating the alkaloid mixture before separation and purification (30). 

The compounds selected for evaluation as potential anticancer agents could be of natural or synthetic origin. Compounds of natural origin have often provided new leads in the novelty of structures with anticancer activity. Mans et al. have enlisted several examples of naturally derived anticancer compounds [35]. For example, vincristine derived from the periwinkle plant Vinca rosea, etoposide is derived from the mandrake plant Podophyllum peltatum, and taxol, which is... 

Bernhardt P, McCoy E, O Connor SE (2007) Rapid identification of enzyme variants for reengineered alkaloid biosynthesis in periwinkle. Chem Biol 14 888-897 Runguphan W, O Connor SE (2009) Metabolic reprogramming of periwinkle plant culture. Nat Chem Biol 5 151-153... 

Amongst these mitotic inhibitors are the Vinca alkaloids isolated from Vinca rosea, the periwinkle plant, of which vincristine and vinblastine are used chemically in the treatment of malignant disease, in particular acute leukaemia. Colchicine, used for many centuries in the treatment of gout, is isolated from the autumn crocus. Griseofulvin, and podophyllotoxin, are isolated from the resin of Podo-phyllum peltatum and used popularly in the treatment of warts. 

Where to chemical syntiiesis is not viaUe then the active imnciple must be obtained either completely or partially from a natural source. Often, however, active principles are present only in minute amounts in material fmn the source plant. The classical example of this situation refers to the anti-leukaemic dimeric alkaloids vincristine and vinblastine from Catharanthus roseus. These compounds may be obtained from the leaves of periwinkle plants grown in the field, but the yield of active principle is less than 0.001% (w/w) making these amongst die most expensive of drugs. Similariy, die content of artemisinin in A. annua has been shown to be rather low and variaUe widiin die range 0.003 -0.21% w/w (8). 

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