Taxol Flashcards
What are the essential medicines powered by plants?
Aspirin, morphine and chemotherapy
How was Taxol discovered?
The 1962 the US national cancer institute collected and screened 114,000 plant specimens
The bark of T. brevifolia was found to have taxanes, a diterpene, which contains paclitaxel
Where was Paclitaxel originally isolated?
Paclitaxel was originally isolated from the bark of the Pacific yew tree Taxus brevifolia
The tree tissues are poisonous with the exception of the fruit (but the seed is also poisonous)
The active pharmaceutical ingredient is present only in small concentrations in the bark, 0.05%
Widely used cancer drug for ovarian and breast cancer
In regards to paclitaxel, what is problematic?
The bark of a 40 foot pacific yew tree 200 years old
Yields 500mg of taxol harvest from felling a tree
3-8 trees are needed per patient
Between 1967 to 1993 where was almost all paclitaxel derived from?
Derived from bark of the pacific yew, Taxus brevifolia
Taxol has poor solubility in water
Water solubility is important because a drug must be fully dissolved to be safe for injection
Any solid particles in an intravenous injection can lead to blood clots
Taxol is dissolved in alcohol with the addition of a soap-like chemical
What is the new source of Taxol?
Corylus avellana L
Taxol in every gram of branches and leaves of hazel is 5mg
Only at about 10% of the concentration in yew trees
But hazel is faster growing and has a wide distribution
What does Paclitaxel do?
Paclitaxel arrests the cell division by stabilizing microtubules
Paclitaxel can pass through the nanopores in the microtubule wall to disrupt mitosis and acts as an antitumour treatment
Taxol prevents disassembly of microtubules
Blocking mitosis blocks cell division
Why is sustainable production of paclitaxel problematic?
Bark extraction
Chemical synthesis
Heterologous expression systems
Semi-synthesis
Plant cell culture
What is a heterologous system?
is a cell or organism that expresses a protein it normally doesn’t, through a process called heterologous expression
What is an example of a heterlogous system?
A taxol heterlogous system is a metabolic engineering approach that uses heterologous expression systems to produce taxol, an anticancer drug
What is semi-synthesis of taxol?
From 10-Deacetylbaccatin-III, a paclitaxel precursor extracted from plantation-grown yew trees using Taxus spp. needles
Four steps to convert precursor to Taxol
What are the different ways to commercially produce taxol?
Extraction- bark (yew tree), inconsistency, high cost
Semi synthesis- precursor to taxol
Plant cell culture- plant cell induction, bioreactor
What is the procedure for plant cell culture of paclitaxel?
Plant source
Explant on solid medium
Primary callus stage
Cell suspension
Aggregates from single cells/small aggregates
Selected strains
Cell suspension
Screening of selected strains
Cryopreservation secure different strains
What is more effective in producing paclitaxel?
Plant cell culture is far more effective than semi synthesis
What is Salicin used to make?
Aspirin
First synthesis in 1899
