Vinca dimer indole alkaloids vinblastine

Vinca dimer indole alkaloids (e.g. vinbiastine) act as spindle poisons. They bind tubulin, inhibiting polymerisation into microtubules, the major elements of the cytoskeleton [100]. Vinblastine itself and its analogue vinoreibine (Navelbine ) [101] are marketed for cancer therapies (Fig. 36). Vinflunine (Javlor ) is a member of second-generation Vinca dimer alkaloids. This 4 -difluoro analogue is more active than vinoreibine in several cancers (Fig. 36). It is now in phase III clinical... 

Vinca dimer indole alkaloids (e.g., vinblastine) act as spindle poison. They bind tubulin, inhibiting polymerization into microtubules, major elements of the cytoske-Vinblastine itself and its analogue vinorelbine (Navelbine ) are marketed for cancer therapies (Figure 4.48). Because of the obvious difficulty in synthesizing such highly complex structures, there were no reports on the preparation of fluorinated derivatives until the remarkable work of Jacquesy s group on the synthesis in super-acidic media. 5 ... 

Vinblastine (4 in Chart 1) and its congeners are dimeric indole alkaloids derived from Catharanthus (Vinca) roseus. Nowadays, the vinca alkaloids constitute an important class of widely and successfully used anticancer agents that inhibit tubulin polymerization [8],... 

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. 

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. 

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, vincaleucoblastine a dimeric indole-indoline alkaloid, m.p. 211-216°C (d.), [a]])-l-42° (CHClj). Structurally, V. is equivalent to a combination of the alkaloids vindoline and catharidine (see Vinca alkaloids). Very low concentrations of V, accompanied by vindoline and catharidine are present in Vinca rosea. V. is one of the most effective naturally occurring antitumor agents, and is used primarily in the treatment of Hodgkin s disease. 

Vinca alkaloids, Catharanthus alkaloids a group of about 60 iridoid indole alkaloids from Vinca (Catharanthus) spp. Structurally, they are tetra- or penta-cyclic indole derivatives with an iridoid component, e g. vindoline, [a]n -18° (CHCI3), m.p. 174-176°C, and vincamine, [ci]d + 41° (pyridine), m.p. 232-233 °C. These are accompanied in the leaves by small quantities (about 0.005%) of two dimeric V.a., i.e. Vinblastine (see) and fincristine (see) (Hg.). Tryptophan and mevalonic acid are biosynthetic precursors... 

The best known drugs acting as antimitotics are the vinca alkaloids, vincristine (7.90) and vinblastine (7.91). They are very complex indole derivatives that nevertheless have been synthesized. Both are quite effective in various leukemias and in Hodgkin s lymphoma, but show considerable neurotoxicity. Vinblastine and vincristine bind specifically to the microtubular protein tubulin in dimeric form, precipitating depolymerization of the microtubules and functionally acting as a mitotic poison. Vinorelbine (7.92) is a semisynthetic vinca alkaloid functionally identical to vinblastine. 

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