PACLITAXEL AS ANTICANCER AGENT: ISOLATION, ACTIVITY, SYNTHESIS AND STABILITY

Paclitaxel, a potent anticancer agent, was first isolated from the bark of Taxus brevifolia in the 1960s and has since become a cornerstone in chemotherapy. Its anticancer efficacy stems from its ability to stabilize microtubules, preventing their disassembly, which inhibits mitosis and ultimately induces apoptosis in cancer cells. This mechanism of action makes paclitaxel particularly effective against a variety of cancers, including ovarian, breast, and non-small cell lung cancer. Despite its clinical success, the isolation of paclitaxel from the Taxus species is limited by low yields and environmental sustainability concerns, prompting the development of alternative synthetic routes. The synthesis of paclitaxel has posed significant challenges due to its complex structure, particularly the C-ring, which is pivotal for its biological activity. Over the years, total syntheses have been achieved using both chemical and semi-synthetic approaches, with the latter being more commercially viable. One notable method involves converting baccatin III, a compound found in Taxus, into paclitaxel via chemical modifications. Stability issues are another hurdle for paclitaxel’s therapeutic use, as its formulation requires careful handling to avoid degradation. It is typically delivered in a solvent formulation, which can sometimes lead to hypersensitivity reactions. Research into enhancing the stability and solubility of paclitaxel formulations is ongoing, including the development of nanoparticle-based drug delivery systems.