Med Chem 2 Flashcards
What is a ‘Bioassay’
Measurement of the concentration/potency of a substance by its effect on living cells or tissues (aka used to test drug candidates)
What 4 things should be taken into consideration when choosing the right bioassay ?
1) Simple (to perform and result interpretation)
2) Quick
3) Relevant
4) In Vitro or In vivo
Give examples of what is used in ‘in vitro’ testing
- Isolated cells
- Enzymes
- Receptors
- Tissue
Give an example of what is used in ‘in vivo’ testing
- Animal model
State 4 advantages of in vitro testing
1) Inexpensive
2) Easier to perform
3) Less controversial
4) Automated (often)
Define ‘Potency’ of a drug
The amount of drug required to achieve a defined biological effect
Define ‘Efficacy’ of a drug
The measure of how effectively an agonist activates a receptor. (Drug can have high affinity for a receptor but low efficacy)
State 5 other advantages of ‘in vitro’ testing
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
What is the literal meaning of ‘in vitro’
‘in the glass’
What is the literal meaning of ‘in vivo’
‘within the living’
State 3 advantages of in vivo testing
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
What balance must be considered w/ in vivo testing
Benefit to risk ratio must always be considered (Good activity at desired target and minimum activity at others = desirable scenario)
State 4 disavantages of in vivo testing (in animals and/or humans)
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
‘In vivo identifies problems which cannot be picked up in vitro’. TRUE or FALSE
TRUE
‘In vitro determines whether drug interacts with target’. TRUE or FALSE
TRUE
‘In vivo tests pharmacokinetic properties’. TRUE or FALSE
TRUE
In Test Validity, ‘automation and easy detection are highly desirable’. TRUE or FALSE
TRUE
‘Robotics’ is an example of HTS. What is HTS ?
High Throughput Screening
What is ‘Robotics’
Automated testing of many compounds (compound library) on a large number of targets. (Several 1000 compounds tested in 30-50 biochemical tests)
State 2 ways of easily measuring robotic compounds
1) Measuring COLOUR CHANGE
2) Radiolabelled ligand (although may not bind to receptor if test compound is already bound -due to higher affinity)
What happens when drug type, drug target and testing system has been determined ?
A lead compound needs to be established. aka A compound that shows the desired pharmaceutical activity (a starting point)
A lead compound can originate from many sources. Name 4 sources (out of 9)
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
State 4 things about sources from NATURAL PRODUCT SCREENING
- 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)
Most biologically active natural products are secondary metabolites. TRUE or FALSE
TRUE
What are the 2 alternatives for synthesising Natural product screening sources in the lab ?
1) Biological extraction
2) Simplify structure for synthesis
Sources from Natural product screening can be taken which pools ?
1) Plant kingdom
2) Microbial world
3) Marine world
4) Animals
3) Toxins/venoms
Taxol (Paclitaxel) (from the Plant kingdom) is an effective anticancer agent. TRUE or FALSE
TRUE
Sources from Medical folklore usually includes experimentation with ….?
berries, leaves and roots
Medical folklore are often useless, dangerous and exhibit Placebo effect. TRUE or FALSE
TRUE
What Chinese herbal medicine acts as an antimalarial agent and may work through synergy
Artemisinin
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
TRUE
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
TRUE and include COMPOUND INTERMEDIATES
Name a synthetic intermediate/ source of compound library that is more active than the target compound.
Isoniazid. (Target compound = isonicotinaldehyde thiosemicarbazone, antitubercular agent)
Describe ‘me too’ drugs sources
Drugs from competing companies used as a starting point.
Structure of existing drug is modified to avoid patent restrictions and therapeutic properties improved.
State an example of a ‘me too’ drug
Captopril (antihypertensive)
State 3 ‘me too’ drugs existing from Captopril
1) Lisinopril (Hoffman-LaRoche)
2) Enalipril (Merck)
3) Cilazapril (Merck)
