Module 4 - Molecular Pharmacology & Drug Design

Question 1

Define ‘semi-synthesis’

Answer 1

The chemical modification of a natural product to produce a new compound.

Question 2

Define optical isomers

Answer 2

Optical isomers have the same binding groups, but in different 3-D positions.

Question 3

What is a S optical isomer (sinister)?

Answer 3

If the compound moves in an anti-clockwise direction.

Question 4

What is a R optical isomer (rectus)?

Answer 4

If the activity of the compound moves in a clockwise direction.

Question 5

Define pKa

Answer 5

pKa was introduced as an index to express the acidity of weak acids. pKa constant is 4.8. The smaller the pKa value, the stronger the acid.

Question 6

Define acid

Answer 6

A molecule which can donate a proton or accept an electron pair on RHS of the dissociation equilibtirum

Question 7

Define base

Answer 7

‘Vacuuming’ protons to deliver a more alkaline system on the RHS

Question 8

Given a pH value, which drug would be more dominant (charged or neutral)

Answer 8

The neutral form (rather than the ionic form) will pass through the membrane to redistribute the drug.

Drug is ‘pulled through’ to the ‘most ionised’ side.

Question 9

Define (electrostatic) ionic bonds

Answer 9

A chemical bond formed between two ions with opposite charges - exchange of electrons.

An interaction between opposite charges

Question 10

Define ion-dipole bonds

Answer 10

An attractive force that results from the electrostatic attraction between an ion and a neutral molecule that has a dipole.

Question 11

Define dipole-dipole bonds

Answer 11

Attractive forces between the positive end of one polar molecule and the negative end of another polar molecule.

Question 12

Define hydrogen bonds

Answer 12

A weak to moderate attractive force that exists between a hydrogen atom covalently bonded to a very electronegative atom and a pair of electrons on another small, electronegative atom, usually F, O or N.

Question 13

Define covalent bonds

Answer 13

Chemical bond that involves the sharing of electron pairs between atoms.

Question 14

Define covalent bonds

Answer 14

Chemical bond that involves the sharing of electron pairs between atoms.

Most drugs do NOT use covalent bonds in their mechanism of action.

Question 15

Which is the strongest intermolecular interaction?

Answer 15

Electrostatic or ionic binding - therefore likely to be the most important in drug-target binding.

Question 16

Define staggered

Answer 16

Staggered conformation is more stable than eclipsed, greater than 60 degrees

Question 17

Define eclipsed

Answer 17

Has an angle of or less than 60 degrees

Question 18

Define anti

Answer 18

Two large groups on adjacent atoms are separated by a 180 degree dihedral angle

Question 19

Define gauche

Answer 19

Has an angle less than 180 degrees

Question 20

Define bioisosteric

Answer 20

Bioisosteric replacement involves the replacement of a particular binding group, so that the new compound will act at the same receptor (often to improve potency or selectivity).

Question 21

Define acetylcholinesterase (AChE)

Answer 21

Enzyme that causes rapid hydrolysis of acetylcholine - cleans up ACh once it’s done what it has to

Its action serves to stop excitation of a nerve after transmission of an impulse.

Question 22

What happens if acetylcholinesterase is inhibited?

Answer 22

Causes a build up in the concentration of acetylcholine in the synaptic cleft, which can result in overstimulation of the cholinergic receptors in the peripheral and central nervous systems.

Question 23

2 types of cholinesterases

Answer 23

1. Acetylcholinesterase (AChE)

2. Butyrylcholinesterase (BChE)

Question 24

What is an antibiotic?

Answer 24

Antibiotics are natural compounds that are produced by microorganisms that thwarts the growth of other microorganisms

Question 25

Gram-positive bacterial cells

Answer 25

Cell-surface is negatively charged (acidic); positively-charged antibiotics penetrate the cell more readily than negatively-charged species.

Question 26

Gram-negative bacterial cells

Answer 26

Difficult to penetrate; some antibiotics are less active against gram-negative compared to gram-positive.

Question 27

What do bacterial cells NOT contain, that eukaryotic cells do?

Answer 27

Sterols; a nucleus; mitochrondria.