Vinca rosea, alkaloids

Separation vinca rosea alkaloids RSil-C18-HL-D 10 urn 250x4.6 gradient Me0H-H20(l l) to (85 15) containing 0.lt ethanolamine 60... 

NMR was very useful in elucidation of the structure of vincristine2. The application of nuclear magnetic resonance spectroscopy to help determine the structures of vinblastine, vincristine, and other Vinca rosea alkaloids is reviewed in several papers 87 88 89. ... 

Since anti-malignant properties in the Vinca rosea alkaloids are apparently confined solely to certain of the dimeric indole compounds, there being no... 

G. H. Svoboda, Antitumoral Effects of Vinca rosea Alkaloids, Proceedings First Symposium of the G.E.C.A. (Groupe Europden de Chimie Therapie Anticancereuse). International Congress Series No. 106. Excerpta Medica Foundation, 1966, p. 9. 

The alkaloid mixture from the extraction of Vinca rosea plants (as in vinblastine extraction) was chromatographed to give vincristine which was then converted to the sulfate, according to U.S. Patent 3,205,220. 

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. 

The discovery of medicinal alkaloids from Catharanthus roseus G. Don (Vinca rosea L.) represents one of the most important introductions of plant products into the cancer chemotherapeutic armamentarium. The relatively unique effects and toxicities of these agents have allowed the design of multiagent chemotherapy programs that have demonstrated sufficient effectiveness to achieve cures even of advanced tumors in many instances. This great accomplishment is possible only because of the inclusion of many different drugs, including the binary Vinca alkaloids. 

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. 

Vinblastine (4) and vincristine (5) are closely related indole-dihydroindole dimers (bisindole alkaloids), isolated from Catharanthus roseus (L.) G. Don (formerly known as Vinca rosea L.), the Madagascar periwinkle. Both of these anticancer agents, known as vinca alkaloids in the medical literature, are specific binders of tubulin, leading to tubulin depolymerization and cell cycle arrest in the metaphase stage. 

Vinblastine and vincristine are alkaloids isolated from plants of the periwinkle family (Vinca rosea). These compounds cause cells to stop at metaphase and inhibit assembly of microtubules, and likewise, failure of mitotic spindle formations. They inhibit synthesis of nucleic acids and proteins. 

The vinca alkaloids are isolated from plant Vinca rosea. They are cell cycle specific and mitotic inhibitors. 

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 is an alkaloid derivative of Vinca rosea and is closely related in structure to vinblastine. Its mechanism of action, mechanism of resistance, and clinical pharmacology are identical to those of vinblastine. Despite these similarities to vinblastine, vincristine has a strikingly different spectrum of clinical activity and safety profile. 

Alkaloid from Vinca rosea (Catharanthus roseus) (Apocynaceae)... 

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. 

The occurrence of catharanthine (XL) is presently confined to Vinca rosea L., and it is the only known iboga alkaloid to contain an olefinic double bond (40). A derivative of this compound makes up the indolic portion of the clinically useful antileukemic drug, vincaleukoblastine... 

A number of alkaloids with the aspidospermine skeleton occur in the genus Vinca and are dealt with in detail in Chapter 12. They include the very important base vindoline (CIII) which not only occurs as the free base in Vinca rosea (= Lochnera rosea = Catharanthus roseus) but also as part of the dimeric alkaloids vinblastine (vincaleucoblastine) and leurosine, whereas the Aa-formyl analog, CIV, forms part of the dimeric alkaloid leurocristine (5, 72a). These dimeric alkaloids have been used successfully for the treatment of certain forms of cancer in man (5). Vindolinine (CVI) has also been isolated from V. rosea and its dihydro-decarbomethoxy derivative, tuboxenin (CVI-A), which is the parent member of the series, occurs in a Pleiocarpa species (53). ( + )-Vincadif-formine (XCIII, 6, 74) has already been mentioned as the racemic form of (— )-6,7-dihydrotabersonine (Section II, O). It has been found in V. difformis and in Rhazya stricta (51b) where the (+) form also occurs. 

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