Drug 2- mech

Question 1

what is chlormethine and how does it work?

Answer 1

• it is a alkylating agent and it causes intrastrand and interstrand cross linking
• prevents replication
• mono-alkylation of guanine also possible

Question 2

what is nitrogen mustard?

Answer 2

• known as chlormethine
• derived from sulfur mustards
• was invented as a 2nd world war chemical agent

Question 3

where is the predominant crosslinks between which 2 species in nitrogen mustards?

Answer 3

N7 of guanine on twwo strands -an interstrand crosslink

Question 4

what exactly does nitrogen mustard do?

Answer 4

stops enzymes such as dna POLYMERASE BEING ABLE TO SEPERATE THE STRANDS

Question 5

what functional ring helps the nitrogen

Answer 5

benzene as it helps it become more controlled and less toxic due to electron being delocalised from N into aromatic ring so can control reactivity on the R group

Question 6

what is cyclophosphamide and how does it work?

Answer 6

its the most commonly used alkylating agent

non-toxic prodrug orally active

Question 7

what is busulfan and how does it work?

Answer 7

its a synthetic agent used as an anticancer agent

causes interstand crosslinking

Question 8

what is dacarbazine and how does it work?

Answer 8

• its a prodrug activated in the liver
• it decomposes to form a methyldiazonium ion
• it methylates guanine groups

Question 9

what is mitomycin c and how does it work?

Answer 9

• its a natural product its a alkylating agent

- one of the most toxic anticancer drug

Question 10

what are metallating agents?

Answer 10

• they are similar to crosslinking

- usually with platinum

Question 11

what is cisplatin and how does it work?

Answer 11

• its a prodrug
• its activated in the cell with low chloride ion conc
• binds to DNA in regions rich in guanine
• intrastrand links rather than interstrand

Question 12

what are chain cutter?

Answer 12

they are agents which will induce DNA strand breaks
anticancer agent
generates radicals

Question 13

what is bleomycins and hows does it work?

Answer 13

-binding with iron ions the amino groups bind to to reaction with oxygen to form radicals
prevents dna ligase from repairing damage

Question 14

what are chain terminators?

Answer 14

-they mimic natural DNA bases
-missing 3’ prime
terminates synthesis of DNA and can inhibit the enzymes used in DNA replication

Question 15

what is AZT and how does it work?

Answer 15

its a prodrug to treat HIV
its phosphorylated to triphosphate in the body
-it inhibits viral enzymes reverse transcriptase

Question 16

what is topoisomerase poisons and how does it work?

Answer 16

• its double helix coil and has to unravel during replication
• unravelled leads to strain
• relieved by enzyme cutting and repair of DNA chain to prevent tangling

Question 17

what are non-intercalating poisons

Answer 17

they stabilise the complex between DNA and topoisomerase enzyme
its an anticancer agents
causes chain cutting

Question 18

what is camptothecin and how do they work?

Answer 18

stabilises complex between DNA and topoisomerase I

single strand breaks accumulate in the chain

Question 19

what are quinolones and fluoroquinilones and and how do they work?

Answer 19

they are synthetic agents used as bacterial agents

• binding sites for agents revealed once DNA strands are “nicked”
• 4 drug molecules are stacked in the bound complex