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Patrick An Introduction to Medicinal Chemistry 3/e Chapter 7 NUCLEIC ACIDS AS DRUG TARGETS Part 3: Section 7.3 (Drugs acting on RNA). 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)
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Patrick An Introduction to Medicinal Chemistry 3/e Chapter 7 NUCLEIC ACIDS AS DRUG TARGETS Part 3: Section 7.3 (Drugs acting on RNA)
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]
4. DRUGS ACTING ON rRNA Antibiotics Streptomycin Chloramphenicol (vs typhoid) Rifamycins Chlortetracycline (Aureomycin) Erythromycin
Protein synthesis 5. DRUGS ACTING ON mRNA Antisense Therapy
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
Azidothymidine (AZT) (Zidovudine;Retrovir) Chain terminating group 6. Drugs related to nucleic acid building blocks Examples: Antiviral agents • 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
Chain terminating group Chain terminating group Acyclovir (Zovirax) Famciclovir (Famvir) 6. Drugs related to nucleic acid building blocks Examples: Antiviral agents Notes: Same mechanisms of action as AZT Used vs herpes simplex and shingles
6. Drugs related to nucleic acid building blocks Examples: Antisense nucleotides - see earlier Uracil mustard - see earlier