What do all of these have in common?

They all contain natural products…

Natural Products Drug

Discovery
Searching for Cures in the Plant
Kingdom
 Primary Metabolites
• Molecules that are
necessary for
survival of organism
• lipids, nucleic acids,
proteins,
polysaccharides
 Secondary Metabolites
• Not essential to the survival of the
organism
• May give the organism a selective
advantage
• Limited distribution in nature taxol
• Also called Natural Products
• Show bioactivity– the ability to
inhibit the growth of microbes
Most natural products have been
found in plants, fungi and
bacteria
 Step 1: Extraction

• Extracts contain all of the

compounds in the cell
• HOW? Add a solvent to
the plant sample.
• Solvents can be either
polar or nonpolar
 Choices, choices…
which solvent to use?
• The solvent is chosen
based on the properties of
the molecule you want to
extract
• Most bioactive compounds
are POLAR.
 How a solvent works
• Solvent breaks the cell
membrane open.
• “Like dissolves like” – the
polar solvent draws out the
polar compounds into
solution
• The smaller the pieces, the
greater the surface area
available for the solvent to
work on the cells.
 Step 2: Microbial Bioassay
• Are the compounds in the extract
bioactive?
– Bioactive = able to inhibit the growth of
microbes
• Test the extract on E. coli (prokaryote) & S.
cerevisiae (eukaryote) – see if extract can
inhibit growth
Prokaryotes vs. Eukaryotes
Prokaryotes Eukaryotes
 Microbial Assay
• Microbe is plated onto
agar plate

• Sterile Discs are dipped

into extract
 Microbial Assay
• Discs are placed on the plate
 Microbial Assay: Controls

• Positive Control = Iodine

• Negative Control = Solvent only

 Positive
Negative Control
Control

Extract
Extract Disc 2
Disc 1
 Zones of Inhibition

• If an extract is bioactive, it
causes a halo to form
around the disc (prevents
growth)
• The size of the halo (the
zone of inhibition)
indicates how effective an
extract is as an
antimicrobial agent.
 Original source of natural product

Extracts prepared

How are Natural

Products Biological testing (Bioassay)

discovered? Fractionation and Purification of active compound(s)

Determination of the Chemical Structure

10-15 yrs.
$83 million Pre-clinical testing (pre-human testing)

Human clinical trials

FDA Approval