Module 4 - Molecular Pharmacology & Drug Design Flashcards
Define ‘semi-synthesis’
The chemical modification of a natural product to produce a new compound.
Define optical isomers
Optical isomers have the same binding groups, but in different 3-D positions.
What is a S optical isomer (sinister)?
If the compound moves in an anti-clockwise direction.
What is a R optical isomer (rectus)?
If the activity of the compound moves in a clockwise direction.
Define pKa
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.
Define acid
A molecule which can donate a proton or accept an electron pair on RHS of the dissociation equilibtirum
Define base
‘Vacuuming’ protons to deliver a more alkaline system on the RHS
Given a pH value, which drug would be more dominant (charged or neutral)
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.
Define (electrostatic) ionic bonds
A chemical bond formed between two ions with opposite charges - exchange of electrons.
An interaction between opposite charges
Define ion-dipole bonds
An attractive force that results from the electrostatic attraction between an ion and a neutral molecule that has a dipole.
Define dipole-dipole bonds
Attractive forces between the positive end of one polar molecule and the negative end of another polar molecule.
Define hydrogen bonds
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.
Define covalent bonds
Chemical bond that involves the sharing of electron pairs between atoms.
Define covalent bonds
Chemical bond that involves the sharing of electron pairs between atoms.
Most drugs do NOT use covalent bonds in their mechanism of action.
Which is the strongest intermolecular interaction?
Electrostatic or ionic binding - therefore likely to be the most important in drug-target binding.
Define staggered
Staggered conformation is more stable than eclipsed, greater than 60 degrees
Define eclipsed
Has an angle of or less than 60 degrees
Define anti
Two large groups on adjacent atoms are separated by a 180 degree dihedral angle
Define gauche
Has an angle less than 180 degrees
Define bioisosteric
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).
Define acetylcholinesterase (AChE)
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.
What happens if acetylcholinesterase is inhibited?
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.
2 types of cholinesterases
- Acetylcholinesterase (AChE)
2. Butyrylcholinesterase (BChE)
What is an antibiotic?
Antibiotics are natural compounds that are produced by microorganisms that thwarts the growth of other microorganisms
Gram-positive bacterial cells
Cell-surface is negatively charged (acidic); positively-charged antibiotics penetrate the cell more readily than negatively-charged species.
Gram-negative bacterial cells
Difficult to penetrate; some antibiotics are less active against gram-negative compared to gram-positive.
What do bacterial cells NOT contain, that eukaryotic cells do?
Sterols; a nucleus; mitochrondria.
