Mechanistic basis of Chemo

Question 1

First cancer drug developed?

Answer 1

Mustine (for Hodgkins lymphoma)

Contain Nitrogen Mustard portion

Question 2

How do topoisomerases facilitate replication and transcription of DNA?

Answer 2

They separate DNA chromosome strands through relaxation then unwind DNA helix then rejoin them again (repaiR)

Question 3

How does the planar aromatic ring structure of intercalating agents aid their action?

Answer 3

They can reversibly slot between DNA base pairs to inhibit replication and transcription by unwinding DNA helix
Hence promoting cell death

Question 4

How are crosslinks formed to damage DNA using alkylating agents?

Answer 4

They attack Guanine (N atom) in DNA 
Twice because two G bases in DNA
2 G bases crosslink together
Altering conformation of DNA
Cannot replicate or transcript... cell death

Question 5

Which R group promotes a faster reaction to form the arizidium ion and why?

Answer 5

Aliphatic groups

Because increase nucleophilic activity of N lp so it can attack CH2 and knock out Cl quicky

Question 6

Which R group promotes a slower reaction to form the arizidium ion and why?

Answer 6

Aromatic groups

Because reduce nucleophilic activity of N lp o it can attack CH2 and knock out Cl slower

Question 7

What kind of side chain must be present in topoisomerase inhibitors to allow it to intercalate into DNA?

Answer 7

Ionic side chain must be present

This keeps it planar (flat) for intercalation

Question 8

What causes cardiotoxicity of anthracyclines?

Answer 8

Anthracyclines form ROS

These promote cardiotoxicity by prolonging QT interval

Question 9

How does Temozolamide (drug affecting nucleic acids) inhibit cancer cell growth?

Answer 9

Methylates O6 position of Guanine (6%)
Forming methylguanine which has no function in DNA formation
Also methylates N7 position of Adenine (70%) - this is the only drug in this class that does both.