Fuchs

• sp^3 = single bonds or isolated heteroatoms
• sp^2 = double bonds or heteroatoms next to double bonds
• sp^1 = triple bonds
• + vs - can be used to denote enantiomers based on the direction the substance rotates plane polarized light
• D vs L can be used to denote enantiomers based on the relative arrangement of substituent groups


  Typically seen on sugars and amino acids (remember, left vs right)
• Typically, two enantiomers will interact with the same target, sometimes with dramatic differences in potency
• Sometimes, other than potency, differences of enantiomers' effects are observed in the metabolism, off-target effects, absorption, and/or clearance
• Synthesis of a single enantiomer of a drug is desirable, however more difficult and expensive
• Chiral resolution


  A method for the separation of enantiomers
• The FDA do not require the preparation of a single enantiomer, but require that sufficient testing of the enantiomers be carried out to assess safety
• Chiral switching


  Changing a drug from a racemic mixture to a single enantiomer
• Conformational analysis


  The examination of the high and low energy forms of a compound
• What is it called when larger groups of a molecule are in a conformation where they are next to each other but still staggered?

  Gauche
• The lowest energy conformer is not necessarily the active conformer
• Secondary metabolites do not have a role in the primary metabolism of the producing organism, rather they tent to have an ecological role (e.g. defensive substances)
• Allelopathy


  Chemical inhibition of one plant by another
• Chemotaxis


  Movement of a cell or organism in the direction of a particular substance
• The study of natural products is Pharmacognosy
• 50% of drugs are from natural compounds and drugs that were in some way based on them
• Vaccines and biologics make up 21% of drugs
• 30% of drugs are purely synthetic
• Natural products occupy a complementary region of chemical space with synthetic compounds
• Ethnobotany


  The relationship between man and his ambient vegetation
• Biodiversity hotspots are estimated to support ~60% of the world's plants
• Bacteria are responsible for 70% of the natural antibiotics produced by microorganisms
• Endophyte


  The microorganisms which reside inside the plant tissues
• Types of biologics

  • Antibody-based
  • Vaccines
  • RNAi
  • Gene Therapy
• Therapeutic genes are packaged in a "delivery vehicle," typically a virus that has been modified to carry human DNA
• Retrovirus


  Delivers RNA into cells to produce a copy of the DNA and incorporate it into the host (INTEGRATED GENE)
• Adenovirus


  DNA is never integrated into the host chromosomes (NON-INTEGRATED GENE)
• An ideal vaccine

  • Activates both T and B cells to produce memory cells
  • Generates Th and Tc cells to the antigens
  • Facilitates the production of high affinity antibodies
• Antibodies are glycoproteins produced by antibody-secreting B cells. They act through binding to antigens on the cell surface.
• Monoclonal antibodies are produced through hybridoma technology wherein two different cell lines are fused together
• Monoclonal antibodies can't be administered orally
• Antibody drug conjugates sneak the monoclonal antibodies into the cell. This allows for the use of more toxic compounds and the discrimination between healthy and diseased tissues
• Proteolysis targeting chimera (PROTAC) is an emerging area of drug development that forces ubiquitin to mark a target protein, leading to its destruction via the proteasome. This allows for complete removal of the target protein
• Most common administration route is orally

  1. Starts in GI tract
  2. Absorbed through the lining of the intestinal or gut wall
  3. Enters the blood
  4. Makes its way to the liver for metabolism
• To get into the bloodstream, the drug must cross the membrane layer (permeability) and be able to be transported in the blood (solubility).
• Physiochemical properties examples


  Molecular size and solubility
• Solid dosage forms are most widely used for administration and as such, solid materials are highly desirable