What do all of these have in common?

Natural Products Drug Discovery Searching for Cures in the Plant Kingdom They all contain natural products…

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 Also called Natural Products Show bioactivity– the ability to inhibit the growth of microbes taxol

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 ProkaryotesEukaryotes

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

Extract Disc 1 Extract Disc 2 Positive Control Negative Control

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.

How are Natural Products discovered? How are Natural Products discovered? 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