Classical Chemotherapy Med Chem Flashcards
What do Nitrogen mustards do?
Stop enzymes such as DNA polymerase being able to seperate strands therefore stopping replication.
Which nitrogen do DNA alkylators bind to mostly?
Crosslink between the N7 of guanine on 2 strands.
What is intrastrand crosslinking?
Where the is bonding between 2 guanine within the same strand.
What is interstrand crosslinking?
Where there is binding between 2 guanine in 2 different strands.
How does DNA Alkylation occur with a mechanism?
Nitrogen donates a pair of electrons which kicks off 1 Cl.
This creates a aziridinium ion.
N7 of guanine donates it pair of electron to the ion which allows it to bind.
This happens again for the other Cl atom.
What is the mechanism of resistance in Aklylating agents?
Increased expression of glutathione-S-transferease and lvls of glutathione
Increase expression of excision of repair enzymes
Chnages the drug uptake.
What is cisplatin used to treat?
Testicular, ovarian, head, neck, loung and bladder cancers.
MOA of cisplatin?
Positively charged aquated platinum reacts with biological nucleophiles.
Biological targte is N7 guanine.
Mechanism of resistance of cisplatin?
Increased repair mechanism for intrastrand crosslinks.
Increased expression of thiol containing proteins.
How do topoisomerase inhibitors work?
Distorts the shape of the double helix.
Inhibit topoisomerease II by preveting it from fixing the double strand break
What do topoisomerase inhibitors need?
Planar polyaromatic ring for DNA intercalation.
Hydroxyl groups to form hydrogen bonds with the DNA bases.
Aromatic ring with OH, NH2 to bind to the minor groove.
Name some Anthracyclines. (Topoisomerease inhibitors)
Doxorubicin
Daunorubicin
Idarubicin
Epirubicin.
What is the mechanism of resistance of topoisomerease inhibitors?
Increased expression of P-glycoprotein
Increased efflux from the cell.
How does anti-mitotic disruption of microtubule assembly work?
disrupts assembly by binding to free aB-tubulin dimers.
Disrupt balance of polymerisation and depolymerisation.
In cancer cells this leads to death by catastrophic mitosis.
How does anti-mitotic inhibition of microtubule dissassembly work?
Stabalisation of microtubule and prevetion of their dissassembly prevents cell replication.
Leads to the formation of abnormal bundles of microtubuli.
