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Anti-microtubule agents

Anti-microtubule agents are plant -derived chemicals that block cell division by preventing microtubule function. Microtubules are an important cellular structure composed of two proteins, α-tubulin and β-tubulin. They are hollow, rod-shaped structures that are required for cell division, among other cellular functions. Microtubules are dynamic structures, which means that they are permanently in a state of assembly and disassembly. Vinca alkaloids and taxanes are the two main groups of anti-microtubule agents, and although both of these groups of drugs cause microtubule dysfunction, their mechanisms of action are completely opposite: Vinca alkaloids prevent the assembly of microtubules, whereas taxanes prevent their disassembly. By doing so, they can induce mitotic catastrophe in the cancer cells. Following this, cell cycle arrest occurs, which induces programmed cell death (apoptosis). These drugs can also affect blood vessel growth, an essential process that tumours utilise in order to grow and metastasise.

Vinca alkaloids are derived from the Madagascar periwinkle, Catharanthus roseus, formerly known as Vinca rosea. They bind to specific sites on tubulin, inhibiting the assembly of tubulin into microtubules. The original vinca alkaloids are natural products that include vincristine and vinblastine. Following the success of these drugs, semi-synthetic vinca alkaloids were produced: vinorelbine (used in the treatment of non-small-cell lung cancer), vindesine, and vinflunine. These drugs are cell cycle -specific. They bind to the tubulin molecules in S-phase and prevent proper microtubule formation required for M-phase.

Taxanes are natural and semi-synthetic drugs. The first drug of their class, paclitaxel, was originally extracted from Taxus brevifolia, the Pacific yew. Now this drug and another in this class, docetaxel, are produced semi-synthetically from a chemical found in the bark of another yew tree, Taxus baccata.

Podophyllotoxin is an antineoplastic lignan obtained primarily from the American mayapple (Podophyllum peltatum) and Himalayan mayapple (Sinopodophyllum hexandrum). It has anti-microtubule activity, and its mechanism is similar to that of vinca alkaloids in that they bind to tubulin, inhibiting microtubule formation. Podophyllotoxin is used to produce two other drugs with different mechanisms of action: etoposide and teniposide.