1. NUCLEIC ACIDS AS DRUG TARGETS
Patrick
An Introduction to Medicinal Chemistry 3/e
Chapter 7
NUCLEIC ACIDS AS
DRUG TARGETS
Part 3: Section 7.3 (Drugs acting on RNA)

2. Contents
Part 3: Section 7.3 (Drugs acting on RNA)
4. Drugs Acting On rRNA
- Antibiotics
5. Drugs Acting On mRNA
- Antisense Therapy (2 slides)
6. Drugs related to nucleic acid building blocks
- Examples: Antiviral agents (2 slides)
- Examples
[7 slides]

3. 4. DRUGS ACTING ON rRNA Antibiotics Streptomycin Chloramphenicol
(vs typhoid)
Rifamycins
Chlortetracycline
(Aureomycin)
Erythromycin

4. 5. DRUGS ACTING ON mRNA
Antisense Therapy
Protein synthesis

5. 5. DRUGS ACTING ON mRNA Antisense Therapy Advantages
Same effect as an enzyme inhibitor or receptor antagonist
Highly specific where the oligonucleotide is 17 nucleotides or more
Smaller dose levels required compared to inhibitors or antagonists
Potentially less side effects
Disadvantages
‘Exposed’ sections of mRNA must be targeted
Instability and polarity of oligonucleotides (pharmacokinetics)
Short lifetime of oligonucleotides and poor absorption across cell membranes

6. 6. Drugs related to nucleic acid building blocks
Examples: Antiviral agents
Azidothymidine (AZT)
(Zidovudine;Retrovir)
Chain terminating
group
Enzyme inhibitor
AZT is phosphorylated to a triphosphate in the body
Triphosphate has two mechanisms of action
- inhibits a viral enzyme (reverse transcriptase)
- added to growing DNA chain and acts as chain terminator

7. 6. Drugs related to nucleic acid building blocks
Examples: Antiviral agents
Acyclovir
(Zovirax)
Famciclovir
(Famvir)
Chain
terminating
group
Chain
terminating
group
Notes:
Same mechanisms of action as AZT
Used vs herpes simplex and shingles

8. 6. Drugs related to nucleic acid building blocks
Examples: Antisense nucleotides - see earlier
Uracil mustard - see earlier