Natural Products (5)

Question 1

Penicillin

Answer 1

• Made from penicillin mold
• Bullet wounds create infection (leading cause of death in world war)
• Penicillin was the first-antibiotic… After this, many anti-biotics were created

Question 2

Origin of New drugs

Answer 2

• Natural products, Synthetic that is based from natural products and derived from natural products

Question 3

How to find natural products in general?

Answer 3

• Insects (strategies to fight off prey)

- Plants (strategies to fight off organisms)

Question 4

How do pharmacists find natural products?

Answer 4

1. Focused screening (ethnopharmacology, 100 yr old healers, plants that treat infections)
2. Random screening
   (looking in unusual places - ocean floor, toxic waste dumps, hot springs/volcanoes, toxins released during an insect competition)

Question 5

Advantages of NP

Answer 5

1. Bioactive (has an effect on living tissue)
2. Bioavailable (rate at which substance is absorbed/ becomes available at the site of problem in body - injection)
   - -> Blood steam is good way - systematic distribution (ADME is controlled)
   - -> type of drug has substance that is similar to compound found in body (easier to reach bloodstream)
   - -> Brain is HARD to reach
3. Produced as simple stereoisomers

Question 6

Racemic drugs

Answer 6

• very easy to synthesize
• One enantiomer is more biologically active
• Less biologically active enantiomer = no activity, toxic (so need to prove if safe in vivo) or has another biological activity.

Question 7

Thalidomide (Chiral center)

Answer 7

• Morning sickness - 1/2 trimesters of pregnancy
• One isomer helped with symptoms, the other one is an inhibitor of angiogenesis of limb development (this is used to treeat cancer and leproxy)
• Racemic mixture occurs in the cycle

Question 8

How does thalidomide’s chiral center change? What happens?

Answer 8

• Racemate = isomerized chiral center

- has to be marketed in a pure enantiomer form

Question 9

How does thalidomide’s “bad” isomer treat cancer or tumours?

Answer 9

• as tumour cells start to grow, the isomer has the ability to rewire blood vasculature in our bodies

Question 10

How to make penicillin orally active?

Answer 10

Ph on original structure can be a substituent – add O or N which will make it EWG or stabilizes acidity