are assembled at one of their ends and disassembled at the other. The microtubules are
hollow tubes built from 13 dimers of two different kinds of protein (αandβ) in a helical
manner. Their outer diameter is about 24 nm. Some cytostatic agents bind to this αβdimer,
preventing its incorporation into the growing microtubule. Several alkaloid natural
products function as antimitotic agents.
7.8.3.1 Vinca Alkaloid Antimitotics
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 lym-
phoma, but show considerable neurotoxicity. Vinblastine and vincristine bind specifically
to the microtubular protein tubulinin 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.
7.8.3.2 Taxane Alkaloid Antimitotics
The alkaloid ester paclitaxel (7.93) is a natural product derived from the western yew
(Taxus brevifolia) and European yew (Taxus baccata). This agent functions as a mitotic
spindle by causing excessive tubulin polymerization. Paclitaxel has demonstrated
considerable clinical utility in ovarian and breast cancer.
ENDOGENOUS CELLULAR STRUCTURES 455