What do all of these have in common?What do all of these have in common?

Natural Products Drug Natural Products Drug DiscoveryDiscovery

Searching for Cures in the Plant Kingdom

They all contain natural products…They all contain natural products…

Primary MetabolitesPrimary Metabolites

• Molecules that are necessary for survival of organism

• lipids, nucleic acids, proteins, polysaccharides

Secondary MetabolitesSecondary Metabolites

• Not essential to the survival of the organism

• May give the organism a selective advantage

• Limited distribution in nature• Also called Natural Products • Show bioactivity– the ability to

inhibit the growth of microbes

taxol

Most natural products have been Most natural products have been found in plants, fungi and found in plants, fungi and

bacteriabacteria

Step 1: ExtractionStep 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…Choices, choices… which solvent to use? 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 worksHow 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 BioassayStep 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. EukaryotesProkaryotes vs. EukaryotesProkaryotes Eukaryotes

Microbial AssayMicrobial Assay • Microbe is plated onto

agar plate

• Sterile Discs are dipped into extract

Microbial AssayMicrobial Assay

• Discs are placed on the plate

Microbial Assay: ControlsMicrobial Assay: Controls

• Positive Control = Iodine

• Negative Control = Solvent only

Extract Disc 1

Extract Disc 2

Positive ControlNegative

Control

Zones of InhibitionZones 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.

How are Natural How are Natural Products Products

discovered?discovered?

10-15 yrs.

$83 million

Original source of natural product

Extracts prepared

Biological testing (Bioassay)

Fractionation and Purification of active compound(s)

Determination of the Chemical Structure

Pre-clinical testing (pre-human testing)

Human clinical trials

FDA Approval