VPI Chemistry

Question 1

The chemistry of imidazoles in terms of acid-base properties

Answer 1

Lower the pKa stronger the acid (ionised at ph values above pKa)

High the pKa the stronger the base (ionised at values BELOW pka)

Question 2

The chemistry of imidazoles in terms of tautomerism

Answer 2

N-subsititued benzimidazoles do not undergo tautomerism

Question 3

Importance of solubililty on ADME

Answer 3

For drugs to be bioavailable they need to be water-soluble

Drugs whose targets are located within cells -> membrane permeability

Both depend on charged status and polarity

Question 4

Importance of partition parameters on ADME

Answer 4

Drugs needs to partition to be bioavailable

Question 5

How can solubilty and partiton parameters be measured/predicted?

Answer 5

Solubility measured by Turbidity (add water to solid until all dissolved determined by cloudiness)

Permeabililty measured across Caco-2 layer

Predict -> LogP <5 + PSA (polar surface area)

Question 6

Process of microtubule synthesis

Answer 6

Microtubules are componets of the cytoskeleton (play role in Mitosis)

Microtubule synthesis are polymers made from protein tubulin (a-tubulin + b-tubulin) bound by nonconvalent bonts

GTP-bound -> polyermisation
Hydrolosis of gtp -> depolymersation

Question 7

Effect of benzimidazole anthelmintics

Answer 7

Anthelmintic benzimidazoles promote microtubule depolymerisation (bind to B-subunit)

Question 8

Effect of benzimidazole anthelmintics

Answer 8

Anthelmintic benzimidazoles promote microtubule depolymerisation (bind to B-subunit)

Question 9

Avermectins are ion channel agonists…? MOA:

Answer 9

Binds to Ion channel
Binding stops the inactivation of the channel
Leads to influx CL ions leading to hyperpolarisation and paralyisis of animal

Question 10

HIV-1 Protease inhibiotors bind to

Answer 10

THe site where the protein cleavage occurs

Question 11

HIV - PI example..?

Answer 11

Ritonavir

Question 12

What are enantiomers

Answer 12

Optical isomers
Identical physiochemical properties
Different pharmacological properties

Question 13

HIV protease cleaves between

Answer 13

Cleaves an aromatic residue P1 & P1’

Question 14

HIV Protease 2 flaps ->

Answer 14

Moves distance of 7a
Apoenzyme
Important h20 molecule mediate H bonding

Question 15

HIV 1 Transition states mimics bind stonger by

Answer 15

drug designed as ‘mimic’ already in the higher energy state (allows more energy to be used in binding sronger)

Question 16

Drug resistance

Answer 16

Incomplete virus eradication during therapy gives virus time to evolve protease mutants

Question 17

Drug resistance due to active site space taking

Answer 17

If the drug protrudes outside of binding site + more likely to exhibit resistance

Question 18

Retrovirus action;

Answer 18

Retro virus attaches to host cell membrane
Virus fuses with membrane taken up in endosome and then uncoated
Viral RNA is RTranscripted into dsDNA
RNA is degraded
1 Dna strand used to make the other
DNA strand intergrated into DNA and translated into viral protein
Assembled then releaseed