Medicinal chemistry 2 - Sources of lead compounds

Question 1

What are bioassays used for?

Answer 1

• used to test drug candidates

- Used in choosing the right bioassay

Question 2

Whata re the four considerations when choosing the right bioassay?

Answer 2

1. Simple
2. Quick
3. Relevant
4. In vitro or in vivo

Question 3

Give examples of targets used in vitro studies?

Answer 3

• Isolated cells
• Tissue
• Enzyme
• Receptor

Question 4

In vivo involves animal model testing. TRUE OR FALSE?

Answer 4

TRUE

Question 5

What are the advantages of in vitro testing?

Answer 5

1. Inexpensive
2. Easier to perform
3. Less controversial
4. Automated (often)
5. No barrier concerns
6. No metabolic enzymes to contend with
7. Cell environment can be easily controlled
8. Can measure potency and efficacy

Question 6

What is potency?

Answer 6

• Amount of drug required to achieve a defined biological effect

Question 7

What is efficacy?

Answer 7

• Measure of how effectively an agonist activates a receptor

Question 8

Drug can have high affinity for a receptor but a low efficacy. TRUE OR FALSE?

Answer 8

TRUE

Question 9

What are the advantages of in vivo testing?

Answer 9

• Important for monitoring pharmacological activity - pharmacodynamics
• Important for monitoring pharmacokinetics (ADME)
• Allows identification of activity at undesired target

Question 10

What is the desired scenario for in vivo testing?

Answer 10

-Good activity at the desired target and minimum activity at others

Question 11

What are the disadvantages of in vivo testing?

Answer 11

• Slow progress
• Animal suffering
• Pharmacokinetics - results may be misleading
• Different results in different animal species

Question 12

Provide an example of different results in different animal species?

Answer 12

• Penicillin methyl ester is hydrolysed in mice and rats but not in rabbits, dogs and humans
• Thalidomide - Teratogenic in rabbits and humans not in mice

Question 13

In vitro determines whether drug interacts with target and in vivo tests pharmacokinetics properties. TRUE OR FALSE?

Answer 13

TRUE

Question 14

In vivo identifies problems which cannot be picked up in vitro. TRUE OR FALSE?

Answer 14

TRUE

Question 15

In test validaty - automation and easy detection are highly desirable. TRUE OR FALSE?

Answer 15

TRUE

Question 16

What does HTS stand for?

Answer 16

High throughput screening

Question 17

What is robotics?

Answer 17

they are auntomated testing of many compounds (compound library) on a large number of targets

Question 18

What happens once drug type, drug target and the testing system have been determined?

Answer 18

• We need to establish a lead compound

Question 19

What is a lead compound?

Answer 19

• A compound showing the desired pharmaceutical activity (a starting point)

Question 20

Name a few sources in which lead compounds can originate from?

Answer 20

• Natural product screening
• Medical folklore
• Screening compound libraries
• Existing drugs “ me too drugs”
• Natures ligands/ modulators
• NMR data

Question 21

Most biologically active natural products are secondary metabolites. TRUE OR FALSE?

Answer 21

TRUE

Question 22

Natural product screening tend to be complex structures and therefore novel. TRUE OR FALSE?

Answer 22

TRUE

Question 23

what pools can we take from for Natural product screening?

Answer 23

• Plant kingdom
• Microbial world
• Marine world
• Animals
• Toxins

Question 24

Give an example of medical folklore drugs?

Answer 24

• Morphine
• Reserpine
• Salicin
• Quinine

Question 25

Whata re compound libraries?

Answer 25

- Coumpounds synthesised but not made it as far as the market place, therefore stored and used against new tragets as they appear on the off chance that they are beneficial

Question 26

Storage of compound libraries are usuallu catalogued based on functionality that is present and will also include compound intermediates on route to a more complex target molecule. TRUE OR FALSE?

Answer 26

TRUE

Question 27

Give an example of a compound library screening?

Answer 27

- Antitubercular agent

Question 28

Isoniazid is the synthetic intermediate for TB but more active than the target compound. TRUE OR FALSE?

Answer 28

TRUE

Question 29

What are me too drugs?

Answer 29

- Using drugs from competing companies as a starting point and modifying the structure to avoid patent restrictions, with approved therapeutic properties

Question 30

Give an example of a me too drug and give its therapeutic use?

Answer 30

- Captopril | - It is an antihypertensive agent