Alkylating Agents Flashcards
alkylating agents are potent _____
electrophiles
alkyl agents alkylate what compounds
purine bases in DNA
(guanine and adenine)
most common place for alkylating agents to add
Guanine N7
what is a bifunctional alkylating agent
produces both intra and inter strand linkages
cell cycle phase that alkylating agents target
non cell cycle specific
if DNA tries to replicate with modification what happens
cell death
could add the wrong bases
agents other than DNA bases that alkylating agents react with?
thiols
cysteine / lysine residues
glutathione (quenches activity)
what happens in long term survivors taking alkylating agents?
second malignancies due to so many mutations
most second malignancies are located where?
bone marrow (leukemia)
cyclophosphamide is activated by what
CYP450
cyclophosphamide becomes what
phorphoramide mustard
what is cyclophosphamide inactivated by
aldehyde dehydrogenase
cyclophosphamide is less toxic why
increased aldehyde dehydrogenase in bone marrow = less bone marrow supression
cyclophosphamide by product
acrolein
acrolein toxicity in cyclophosphamide
hemorragic cyctitis
cyclophosphamide given with what to avoid acrolein toxicity
mesna
mesna accumulates where
urine, bladder
which alkylating agent is a prodrug
cyclophosphamide
mitomycin C dose limiting side effect
myelosupression
mitomycin C mechanism
bifunctional cross links
are platinum compounds alkylating agents?
no, covalent crosslinkers
platinum compounds cross link ____
intrastrand
platinum compound geometry effect onDNA
can create sharp bends in strands that make DNA repair difficult
cisplatin produces what types of cross links
intrastrand
