What do all of these have in common
- Slides: 17
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 • 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 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
Negative Control Extract Disc 1 Positive Control Extract Disc 2
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 How are Natural Products discovered? 10 -15 yrs. $83 million 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
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