Chemical Report on Taxol (Paclitaxel)
By
Lenel Metayer
Abstract
Taxol is a drug used specifically for microtubule destabilization. Doing so allows it t control the
growth of cells and is useful towards cancer treatment. Taxol is made from the compound Paclitaxel
(CAS Number – 33069-62-4)3. The compound is a very complex combination of multiple esters, singular
amide, multiple arene, and a central 3 ring system (Figure 1). Taxol is known to be insoluble, which can
cause issues when related to drug development. It appears as a white powder or as needles if from
methanol. The compound is very stable due to it having a melting point of 215◦C and shows no
decomposition3.
Background
Figure 1 Image of Taxol 9
The Paclitaxel in Taxol is a cytostatic agent that was founded in 1970. The compound was
isolated from the bark of a Western Yew tree. Paclitaxel effectively binds to tubulin to affect mitotic
processes. It is done so by inhibiting the biding of microtubules. Since Paclitaxel is insoluble, Taxol also
contains polyoxyethylated caster oil and ethanol to form micelles in aqueous environments. 9
Paclitaxel is found in low concentrations in plants. The production of paclitaxel can be presented
in figure 2. Even with the steps presented, the intricate structure of the compound leaves the presented
pathway incomplete. The complex nature of this compound makes chemical synthesis non commercially
sound and release toxic byproducts1. Instead, an idea presented by Bristol Myers Squibbs was to extract
paclitaxel intermediates. This still presents issues such as environmental factors for the plant, purification
fees of the intermediate, and the tree that creates it is slow growing. Another method discovered was to
insert genes into other organisms to create the intermediates. However, in bacteria such as E. coli, the
functionality of these genes goes to waste due to translation and insertion issues. For the plants that could
produce it such as tomatoes, the amount gather was very minimal due to the complexity of the compound.
There was a discovery however with cambial meristematic cells (CMC)1. These cells essentially act as
stem cells. They have lower variability with growth and are less sensitive to stress. They can produce up
to five times the amount of paclitaxel and are the chassis for future metabolic engineering.
Figure 2 Biosynthesis of Paclitaxel1
Analysis
Figure 3 Paclitaxel on Mitosis7
Paclitaxel effectiveness comes from targeting microtubules. The compound promotes the
polymerization of microtubules and inhibits the disassembly of it. It is done so by binding to the Nterminal 31 amino acids of the beta tubulin in microtubules8. By doing so, this disrupts the mitotic
processes of a cell due to microtubules playing a huge role in interphase. Further causing disruption
during cell division and the create of incomplete cells (figure 3). Allowing to be useful towards the
treatment of multiple kinds of cancer such as lung, breast, ovarian, and neck. Also, as a complementary
effect, it increases the effects of ionizing radiation8. Allow chemotherapy to be more effective. The only
forms of resistances to paclitaxel found is that it can speed up the formation of defective tubulin into
microtubules. Some tumor cells also have proteins in their membranes that act drug-efflux pumps8.
Toxic effects that the drug has implements hematologic and neural effects. Neutropenia is a toxic
side effect of Paclitaxel. It is when there is a low white blood cell count within the body. It takes places
usually 10 days after treatment and takes roughly 21 days to recover. Another toxic side effect will be
numbness and paresthesia. It can occur within 1 to 3 days8.
As it currently stands, patents for Taxol are within legal distress. The company that aided in
Paclitaxel development Bristol Myers Squibbs claimed to have ownership over the drug.5 Leaving it for
broad competition in terms of ownership and creation. However, that company is still the leading
producing for the unpatented drug.
Conclusion
Taxol is created from the compound Paclitaxel. It has a complex structure and is unique to certain
plant in terms of natural biosynthesis. Due to the positive effects, it can have for cancer/tumor treatment,
multiple ways have been approached for bioengineering it. An effective way is using CMCs to
biosynthesize it for us, due to other methods yielding little to no quantities of Paclitaxel. The drug affects
the microtubules within a host to affect the mitotic process of a cell. Allowing the demise of cancer cells
while having the chance of hematologic and neural toxic side effects.
References
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