Unit 9 Taxol Flashcards
Where does taxol come from?
From bark of Pacific yew tree. (Taxus brevifolia)
low concentration, slow growing tree
- fund in tree but not made by tree
- Made by Taxomyces andranae (endophytic fungus of Pacific Yew tree)
Where are the regions with most taxol production/growth
located?
Western forests of Canada and the USA.
Plentiful in National Forests of Oregon
What is the importance of Taxol?
It is currently used as chemotherapeutic drug.
Fights cancer, Breast cancer specially.
Let’s us know the importance of basic research in Chem, Medicine and Biol
Synthesis
Made synthetically - compound difficult to make because of many chiral centers (11)
Relying on biosynthesis in natural environemnt is unpractical - Need 300,000 kg of bark to obtain only 25 kg of taxol
(around 3 trees per patient)
Synthetic Precursor
10-Deacetyl Baccatin III
-Precursor for Taxol and Taxotere –> different compounds / drugs.
Taxol’s Mechanism of Action
Stabilization of the microtubules to avoid their polymerization and depolymerazation.
- This inhibits cell division and mitosis because the tubulin polymers (coming from microtubules) are the ones that pull the chromosome to the centrioles.
Affects mitosis and cytoskeleton directly
Colchicine
used for microtubule dissassembly.
Used for studying cancer - taxol is used to treat cancer
How was taxol identified?
- Taxomyces andranae was isolated from phloem (inner bark) of Pacific Yew Taxus brevifolia
- Grown in semi-synthetic liquid media –> shown to produce taxol and related compounds
- Detection by mass spectrometry, chromatography, mAB reactivity specific for taxol.
Why does Taxol mechanisms of action make it useful for chemotherapies?
It prevents cell division and mitosis by halting polymerization and depolimerization (stabilization of microtubules)
chiral centers taxol vs taxotere
Both have 11
10-deacetyl - baccatin III has 9
