Vinca

Several of the naturally occurring indoles also have clinical importance. The dimeric vinca alkaloid vincristine and closely related compounds were among the first of the anti-mitotic class of chemotherapeutic agents for cancer[14]. The mitomycins[15] and derivatives of ellipticine[16] are other examples of compounds having anti-tumour activity. Reserpine, while not now a major drug, was one of the first compounds to show beneficial effects in treatment of mental disorders[17]... 

Among the examples of monoindole bases being discussed, vincamine (109) is the principal alkaloid of Vinca minorC. and has received some notoriety because it apparently causes some improvement in the abiUties of sufferers of cerebral arteriosclerosis (78). It is beheved that this is the result of increasing cerebral blood flow with the accompanying increase in oxygenation of tissue as a result of its action as a vasodilator. 

Vinpocetine (2), another dmg initially categorized as a cerebral vasodilator, is a member of the vinca alkaloid family of agents (7). However, interest in this compound as a potential dmg for learning and memory deficits comes from its abiUty to act as a neuronal protectant. This compound was evaluated in 15 patients with AD over a one-year period and was ineffective in improving cognitive deficits or slowing the rate of decline (8). However, in studies of patients with chronic vascular senile cerebral dysfunction (9) and organic psycho syndrome (10), vinpocetine showed beneficial results. 

Vindoline [2182-14-1] (45), a monomeric Vinca alkaloid intermediate important in the synthesis of antineoplastic alkaloids, is selectively converted in good yield to 0-desmethylvindoline [68687-22-9] (46) by cultures of Sepedonium chrysospermum (17,25), whereas Streptomyces albogriseolus removes only the A[-methyl group to give (47) (91) (see Chemotherapeutics, anticancer). 

In addition to the Vinca alkaloids and taxol, a limited number of other cytotoxic agents have been demonstrated to act at the level of tubulin. This... 

Vincarpin and Dihydrovincarpin are two additional examples of pseudo-cross-conjugated mesomeric betaines. They were isolated from Vinca major elegantissima (76TL4887) (Scheme 82). 

Uiiergrlin, n. periwinkle, myrtle (Vinca). iniiierhm, adv. still, after all, at any rate. gunersionsflussigkeit, /. immersion liquid, miner-wahrend, p.a. everlasting, perpetual. 

Singriin, n. periwinkle, myrtle (Vinca). singular, a. singular. 

Sinngrim, n. periwinkle, myrtle (Vinca). sinn-ig, a. sensible thoughtful ingenious pretty, -lich, a. sentient, sensitive, sensuous, sensual, -los, a. senseless. 

Vinca rosea plants Benzene Sulfuric acid... 

According to U.S. Patent 3,225,030, 1,500 grams of dried ground plant of Vinca rosea were Intimately mixed with 1,000 ml of a 2% tartaric acid solution, and the mixture was extracted with three 9-liter portions of benzene. The benzene extracts were combined and were concentrated in vacuo to about 1,500 ml. The concentrate was mixed with 1 liter of 2% tartaric acid and the mixture was steam-distilled under reduced pressure until all of the benzene had distilled over. The insoluble residue was dissolved in hot methanol, a second 1-liter portion of 2% tartaric acid solution was added, and the mixture was steam-distilled under reduced pressure until all of the methanol had distilled. 

Further elution of the above chromatographic column with a 50 50 benzene-chloroform solvent mixture or with a 25 75 benzene-chloroform solvent mixture serves to elute vinca-leukoblastine. Vincaleukoblastine also occurs in the latter fractions containing leurosine. Vincaleukoblastine is obtained from vincaleukoblastine-containing fractions by evaporation... 

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. 

Ngan VK, Bellman K, Hill BT et al (2001) Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine. Mol Pharmacol 60 225-232... 

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. 

Vincristine and vinblastine (vinca alkaloids) comprise another class of drugs that inhibit the polymerization of microtubules but do so by binding to the tubulin molecule at a site different from the colchicine site. Cultured cells exposed to high concentrations of vinca alkaloids develop intracytoplasmic paracrystalline aggregates of tubulin. These drugs are employed clinically in cancer chemotherapy to inhibit the growth of tumors composed of rapidly dividing cells. 

Another drug is taxol, which is extracted from the bark of the Pacific yew tree, Taxus brevijolia. Unlike colchicine and the vinca alkaloids, taxol binds tightly to microtubules and stabilizes them against depolymerization by Ca. It also enhances the rate and yield of microtubule assembly, thereby decreasing the amount of soluble tubulin in the cytosol pool. Again, the overall effect of taxol is to arrest dividing cells in mitosis. Taxol is used in cancer chemotherapy. 

C7H13N 13375-29-6) see Rilmenidine 3, 4 -didehydro-4 -deoxy-6 -[(trifluoroacetyl)oxy vinca-leukoblastinium mono(triiluoroacetate)... 

Certain drugs bind to microtubules and thus interfere with their assembly or disassembly. These include colchicine (used for treatment of acute gouty arthritis), vinblastine (a vinca alkaloid used for treating certain types of cancer), paclitaxel (Taxol) (effective against ovarian cancer), and griseoflilvin (an antifungal agent). 

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