Antineoplastic agents taxanes

Vinca alkaloids (vincristine, vinblastine, vinorelbine) are derived from the periwinkle plant (Vinca rosea). These agents work by binding to tubulin at a site different than colchicine or paclitaxel. They block polymerization, which prevents the formation of the mitotic spindle, and are used as antineoplastic agents. Taxanes produce a stabilization of microtubules similar to colchicine, but by a different mechanism, and also halt cells in metaphase. Paclitaxel (taxol) is the taxane used clinically. It is derived from the bark of the pacific yew. Taxol disrupts several microtubule-based functions as completely as inhibitors of polymerization, emphasizing the importance of assembly/disassembly balance in microtubule function. Recently, it has been found that paclitaxel also binds to and inhibits the function of a protein called bcl-2, an inhibitor of one or more pathways involved in mediating apoptosis. PaclitaxeTs interference with this function promotes apoptosis in addition to its microtubule-related inhibition of cell division. 

The taxane antineoplastic agents (paditaxel and docetaxel) act by promoting formation and stabilization of microtubules. Accumulation of these polymerized microtubules may lead to mitotic arrest and cell death from nonfunctional tubules. They are considered to be cell cycle-specific agents (acting with greatest activity on cells in Gap 2 [Gj] and mitosis [M] phases). 

Many other alkaloid-based medicines exist. Drugs based on berberine are used in the treatment of infections as well as in the treatment of AIDS. The taxanes (e.g., paclitaxel in Taxol drug and its synthetic analogue, docetaxel in Taxotere) have antineoplastic agents to cure cancers, Kaposi s sarcoma, and squamous cell carcinomas. Several novel alkaloids and their synthetic analogues are under development and considered to being accepted by U.S. Food and Drug Administration for clinical use. ... 

Thbulin-polymerizing chemotherapeutic agents, such as taxanes, have been shown to be one of the most effective drug classes in the treatment of ovarian cancer. The clinical success of paclitaxel has stimulated research into compounds with similar modes of activity in an effort to emulate its antineoplastic efficacy while minimizing its less desirable aspects, which include non-water solubility, difficult synthesis, and emerging resistance. 

---