Principles of Bioorganic Medicinal Chemistry

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Principles of Bioorganic Medicinal
Chemistry Drugs Medicinal Chemist
Lovastatin-Mevacor
August 26/2002.
Zbigniew J. Witczak, Ph.D.
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Principles of Bioorganic Medicinal Chemistry
PHA 598A Dr. Zbigniew J. Witczak

• Learning Objectives
• 1. Describe the mechanism by which cell
  macromolecules mediates the cellular response.
• 2. Identify the cell components and active
  macromolecules that are involved in the
  development and regulation of the cellular
  processes and drug action/response.
• 3. Identify the pharmacological responses by
  which the therapeutic agents acts in the multiple
  cellular system.
• 4. Identify the chemical aspects of drug action
  and their pharmacological responses.

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Clasification of Drugs

• by pharmacological effect
• by chemical structure
• by target system
• by site of action

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By pharmacological effect

• analgesics
• antipsychotics
• antihypertensive
• antiasmathics
• antibiotics
• anticonvulsant (sedative agents)

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By chemical structure

• Opiates
• Steroids
• Barbiturates
• Penicilins
• Cateholamines

Penicillin V
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• Why should drugs work?
• Cell/cell membranes
• Where do drugs work?
• Cell/cell membranes
• Nucleus- control centre for the cell

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Molecular Targets in the Cell Affected by Drugs

• Lipids
• Proteins (Glycoproteins)
• Nucleic acids

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Fatty acids and other lipids.
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Fatty acids and other lipids.
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Therapeutic Index

• Measure of the ratio of undesirable to desirable
  drug effects.
• For in vivo systems thee therapeutics index
  could be the ratio of the LD50
• ( the lethal dose for 50 of the test
  animals) to the ED50 ( the effective
• dose that produces the maximum therapeutic
  effect in 50 of the test animals.
• The larger the therapeutic index the greater the
  margin of safety of the drug!!!!.

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Hydrophilic
Hydrophilic
Hydrophilic
Hydrophobic Region
Amphotericin B

• Amphotericin B interacts with the lipids of
  fungal cell membranes
• Build Tunnels through the membrane
• The contents of the cell is drained away
• Cell is killed

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Inhibitors of Glycosphingolipid Biosynthesis