Lecture 6 - Cancer drug discovery Flashcards
What is camptothecin and how does it work?
It is a cancer drug derive from plant material and its activity is due to the hydoxylactone group. It works by inhibition of topoisomerase I which is involved in replication, transcription and recombination.
Give examples of derivatives of camptothecin.
Irinotecan - Used for metastatic colorectal cancer. Reduced toxicity and more soluble than CPT.
Topotecan - It is a prodrug which is metabolised in the body. It is 1000x more potent than camptothecin and used for metastatic ovarian cancer
Why is taxol such an important discovery?
Taxol was extracted from from yew trees in very small amount. It proved to be effective against solid tumours. Taxol was found to be using a new mechanism of action against cancer and that was by inhibiting depolymerisation of microtubules back to tubulin.
It was also one of the few drugs that was later on derived by semi synthetic approach. Obtaining the active ingredient from the natural source proved to be tedious and expensive, so an intermediate was extracted from needles and it was synthesised to the final product.
Where is podophyllotoxin extracted from and give examples of its analogues.
Give its mechanism of action.
It is extracted from a perennial namely podophyllum peltatum. There is 2 analogues of podophyllotoxin; etoposide and teniposide. These are both very potent, used in small cell lung cancer, testicular and lymphoma.
Podophyllotoxin works by prevent formation of microtubule. Etoposide and teniposide inhibit topoisomerase II - prevent DNA synthesis and replication.
What is the advantage of using alkaloids in cancer?
They inhibit the enzyme glycosidase which is involved in the synthesis of tumour associated carbohydrate antigens.
These surface carbohydrates are believed to give tumour metastatic properties. So using alkaloids provides a potential to treat metastatic cancers.
Where is cyanohydrins present and how can it be used on cancer?
It is a toxin found is bitter almond and cassava but it is normal bound to a sugar which makes it non toxic. Cyanohydrins can be used as a prodrug where it is broken down in the body to form HCN which will attack the tumour.
