Med Chem 2

Question 1

What is a ‘Bioassay’

Answer 1

Measurement of the concentration/potency of a substance by its effect on living cells or tissues (aka used to test drug candidates)

Question 2

What 4 things should be taken into consideration when choosing the right bioassay ?

Answer 2

1) Simple (to perform and result interpretation)
2) Quick
3) Relevant
4) In Vitro or In vivo

Question 3

Give examples of what is used in ‘in vitro’ testing

Answer 3

• Isolated cells
• Enzymes
• Receptors
• Tissue

Question 4

Give an example of what is used in ‘in vivo’ testing

Answer 4

• Animal model

Question 5

State 4 advantages of in vitro testing

Answer 5

1) Inexpensive
2) Easier to perform
3) Less controversial
4) Automated (often)

Question 6

Define ‘Potency’ of a drug

Answer 6

The amount of drug required to achieve a defined biological effect

Question 7

Define ‘Efficacy’ of a drug

Answer 7

The measure of how effectively an agonist activates a receptor. (Drug can have high affinity for a receptor but low efficacy)

Question 8

State 5 other advantages of ‘in vitro’ testing

Answer 8

1) No barrier concerns, therefore no worries as to whether drug can cross any biological barriers (as seen in vivo)
2) No metabolic enzymes to compete with
3) Cell environment can be easily cotrolled
4) Intra and Intercellular events can be monitored easily
5) Potency and efficacy can be measured

Question 9

What is the literal meaning of ‘in vitro’

Answer 9

‘in the glass’

Question 10

What is the literal meaning of ‘in vivo’

Answer 10

‘within the living’

Question 11

State 3 advantages of in vivo testing

Answer 11

1) Important for monitoring pharmacological/pharmacodynamic activity (effect of drug on the body)
2) Important for monitoring pharmacokinetic activity (effect of body on drug, ADME)
3) Allows for identification of activity at undesired targets

Question 12

What balance must be considered w/ in vivo testing

Answer 12

Benefit to risk ratio must always be considered (Good activity at desired target and minimum activity at others = desirable scenario)

Question 13

State 4 disavantages of in vivo testing (in animals and/or humans)

Answer 13

1) Slow progress
2) Animal suffering
3) Pharmacokinetics (results may be misleading- intraspecies variation)

4) Different results in diff animal species
- e.g: 1) Penicillin methyl ester (prodrug) is hydrolysed in mice and rats but NOT in rabbits, dogs or humans
2) Thalidomide - Teratogenic in rabbits and humans and NOT in mice

Question 14

‘In vivo identifies problems which cannot be picked up in vitro’. TRUE or FALSE

Answer 14

TRUE

Question 15

‘In vitro determines whether drug interacts with target’. TRUE or FALSE

Answer 15

TRUE

Question 16

‘In vivo tests pharmacokinetic properties’. TRUE or FALSE

Answer 16

TRUE

Question 17

In Test Validity, ‘automation and easy detection are highly desirable’. TRUE or FALSE

Answer 17

TRUE

Question 18

‘Robotics’ is an example of HTS. What is HTS ?

Answer 18

High Throughput Screening

Question 19

What is ‘Robotics’

Answer 19

Automated testing of many compounds (compound library) on a large number of targets. (Several 1000 compounds tested in 30-50 biochemical tests)

Question 20

State 2 ways of easily measuring robotic compounds

Answer 20

1) Measuring COLOUR CHANGE

2) Radiolabelled ligand (although may not bind to receptor if test compound is already bound -due to higher affinity)

Question 21

What happens when drug type, drug target and testing system has been determined ?

Answer 21

A lead compound needs to be established. aka A compound that shows the desired pharmaceutical activity (a starting point)

Question 22

A lead compound can originate from many sources. Name 4 sources (out of 9)

Answer 22

1) Natural product screening
2) Existing drugs (‘me too’ drugs)
3) Medical folklore
4) Screening compound libraries

5) NMR data
6) Computer aided design
7) Natures ligands/modulators
8) Combinatorial synthesis
9) Serenpidity

Question 23

State 4 things about sources from NATURAL PRODUCT SCREENING

Answer 23

• A rich source
• Most biologically active natural products are secondary metabolites
• Tend to be complex structures therefore novel
• Generally hard to synthesise in the lab (Either perform biological extraction OR simplify structure for synthesis)

Question 24

Most biologically active natural products are secondary metabolites. TRUE or FALSE

Answer 24

TRUE

Question 25

What are the 2 alternatives for synthesising Natural product screening sources in the lab ?

Answer 25

1) Biological extraction

2) Simplify structure for synthesis

Question 26

Sources from Natural product screening can be taken which pools ?

Answer 26

1) Plant kingdom
2) Microbial world
3) Marine world
4) Animals
3) Toxins/venoms

Question 27

Taxol (Paclitaxel) (from the Plant kingdom) is an effective anticancer agent. TRUE or FALSE

Answer 27

TRUE

Question 28

Sources from Medical folklore usually includes experimentation with ….?

Answer 28

berries, leaves and roots

Question 29

Medical folklore are often useless, dangerous and exhibit Placebo effect. TRUE or FALSE

Answer 29

TRUE

Question 30

What Chinese herbal medicine acts as an antimalarial agent and may work through synergy

Answer 30

Artemisinin

Question 31

Sources from compound libraries are stored and used against new targets (as they haven’t made it into the market place yet). TRUE or FALSE

Answer 31

TRUE

Question 32

Storage of compound libraries are usually catalogued based on functionality. TRUE or FALSE, and include ……on route to a more complex target molecule. Fill in the gap

Answer 32

TRUE and include COMPOUND INTERMEDIATES

Question 33

Name a synthetic intermediate/ source of compound library that is more active than the target compound.

Answer 33

Isoniazid. (Target compound = isonicotinaldehyde thiosemicarbazone, antitubercular agent)

Question 34

Describe ‘me too’ drugs sources

Answer 34

Drugs from competing companies used as a starting point.

Structure of existing drug is modified to avoid patent restrictions and therapeutic properties improved.

Question 35

State an example of a ‘me too’ drug

Answer 35

Captopril (antihypertensive)

Question 36

State 3 ‘me too’ drugs existing from Captopril

Answer 36

1) Lisinopril (Hoffman-LaRoche)
2) Enalipril (Merck)
3) Cilazapril (Merck)