Vinblastine

The medicinal properties of Catharanthus roseus have been described in the traditional and folk medicine of several countries. The beneficial effects of its extract in diabetes mellitus were known, but later on active principles suppressing neoplasm were also isolated. The extracts yielded four active dimeric monoterpenoid indole alkaloids - vinblastine, vincristine, vinleurosine and vinrosidine. The catharanthus alkaloids are cell-cycle-specific agents, similar to colchicine and podophyllotoxin, block mitosis and cause metaphase arrest. Though vincristine and vinblastine have antiproliferative properties, both have different patterns of cytotoxic effect and have been used in combination for the last 40 years (FDA approval received in 1963 and 1965, respectively) [73].

Navelbine (Vinorelbine), vinblastine (Velban) and vincristine (Oncovin) are currently used clinically [74]. Vinblastine introduces a wedge at the interface of two tubulin molecules, thus interfering with tubulin assembly and inducing self-association of tubulin into spiral aggregates at the expense of microtubule growth, which may be an attractive target for drug designing [75]. Several analogues of vin-blastine and vincristine are also in clinical use (Table 10.1), such as vinorelbine and vindesine [76].

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