Alkaloid from Vinca rosea

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

Neuss N, Gorman M, Svoboda GH, Maciak G, Beer CT. Vinca alkaloids. IB. Characterization of leurosine and vindaleukoblas-tine, new alkaloids from Vinca rosea Linn. J. Am. Chem. Soc. 1959 81 4754-4755. 

NSC 49842 Velban Velbe ) is one of the vinca alkaloids from Vinca rosea (Catharanthus roseus) (Apocynaceae). It is a cytotoxic ANTICANCER AGENT used by injection for acute leukaemias, lymphomas and some solid tumours, vinblastine sulfate vinblastine, vincaleucoblastine vinblastine, vincaleukoblastine vinblastine. 

Other alkaloids from Vinca rosea show a different property vincolidine, lochrovicine, catharanthine (172), and vindolidine have been shown to possess diuretic activity.Vindolidine has been found to be a potent diuretic, but because of the availability of other harmless diuretics, these alkaloids have not been used for this purpose. 

Jakovljevic et al. [95] have separated eight alkaloids from Vinca rosea on an alumina layer which they had prepared with 0.5 N lithium hydroxide solvents were acetonitrile-ethanol (95 + 5) or benzene-acetonitrile (70 + 30) and sdsualisation was carried out with cerium(IV)-stilphate (Rgt. No. 34). According to [95] it is better to dilute this reagent solution with an equal volume of water before use. Moza and TrojAnek [142] also comment on the advantages of TLC over PC on an alumina layer, using petrol ether-anhydrous ether (50 + 50),... 

The discovery of the anticancer properties of the alkaloids of Vinca rosea constitutes a particularly beautiful example of pharmacological feed-back. Preparations from this plant had the reputation in some popular medicines to possess antidiabetic virtues. During a controlled pharmacological test, these extracts were proven to be devoid of hypoglycemic activity. On the other hand, it was frequently... 

In 1959 a series of bisindole alkaloids were isolated from Vinca rosea L. Catharanthus roseus G. Don). Of signal importance have been vinblastine (169) (= vincaleukoblastine) and vincristine (170) (= leurocristine), both of which show anti-tumour activity (see Section 18, p. 333). Structurally clarified also are leurosidine (= vinrosidine), leurosine, pleurosine, and isoleurosine , while only one half of Catharine is known. 

Leurosidine (181).— The third bisindole alkaloid of this group from Vinca rosea L. to be investigated was leurosidine (181), C46H58O9N4 (= vinrosidine), an isomer of vinblastine (169). 

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... 

So far about 72 alkaloids have been isolated from Vinca rosea Liim, genus Catharanthus roseus (Family Apocynaceae). Out of these 24 dimeric alkaloids only six possess antineoplastic activity but specifically two i.e., vincristine, vinblastine, are used clinically in human neoplasms. These are cell-cycle specific agents. 

The antibiotic griseoviridin (60) has been mentioned (see Section 9.27.3.3). The antitumor alkaloid vinblastine (411) (from Vinca rosea) is used widely in the treatment of Hodgkin s disease <89CC518>. The dibenz[(//]azonine alkaloids neodihydrothebaine (412 R = OMe, = H) and bractazonine (412 R = H, R = OMe) have been isolated from Papaver bracteatum <84H(22)2007> (see also... 

Vincristine, leurocrisliae a dimeric indole alkaloid closely related to vinblastine, from Vinca rosea (see Vinca alkaloids). It is used mainly for the treatment of acute leukemia in children, and against various other neoplasmic growths. 

Vincamine (CV) [1089], one of the monoterpenoid-derived indole alkaloids of Vinca minor L., which are quite different in chemical structure from the alkaloids occurring in Vinca rosea, is of interest mainly on account of its ability to produce a sustained h5q)otension - a property also characteristic of the total alkaloids of Vinca rosea [1090-1092]. A number of the studies with vincamine... 

In 1958, a most curious paper appeared in the Annals of the New York Academy of Science in which even the authors suggested that its appearance was unorthodox. The work was entitled Role of Chance Observations in Chemotherapy Vinca rosea" and needs to be read to be enjoyed. In this work, the authors describe following activity in extracts from Vinca rosea Linn, (now called Catharanthus roseus) through a series of purifications cycles until crystalline material of plant alkaloid is obtained. 

Noble RL, Beer CT, Cults JH (1958) Further biological activities of vincaleukoblastine - an alkaloid isolated from Vinca rosea (L). Biochem Pharmacol 1 347-348... 

Shimizu M, Uchimaru F 1958 Isolation of alkaloids from Vinca Lochnera) rosea. Chem Pharm Bull 6 324... 

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. 

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. 

---