Antibiotics 2 W8

Question 1

What are azoles

Answer 1

organic compounds characterized by a five-membered heterocyclic ring containing at least one nitrogen atom and at least one other non-carbon atom

widely used as antifungal medications and fungicides

Question 2

Lanosterol can go 2 ways:

Answer 2

Cholesterol or ergosterol

Question 3

How lanosterol to cholesterol

Answer 3

Mammals have an enzyme that lanosterol converts into cholesterol

Question 4

How lanosterol to ergosterol

Answer 4

Fun guys don’t have the same enzyme as mammals and so instead of cholesterol being produced ergosterol is produced

Question 5

What does this tell us?

Answer 5

By inhibiting the enzyme that converts lanosterol into ergosterol it is then not produced and does not affect mammals as it is essential for fungi survival

Question 6

What happens if we inhibit squalene which is the step before lanosterol

Answer 6

We then stop both cholesterol and ergosterol and this is toxic

Question 7

Mode of action of Azoles

Answer 7

Inhibit the C-14 demethylation of steroles

Question 8

How do azoles bind

Answer 8

They are a five member ring with two nitrogen atoms and one of those nitrogen atoms with a lone pair binds to iron which is then bound to 4 more nitrogen atoms.

Question 9

What structure is critical?

Answer 9

The five membered ring with two nitrogen of a azole

Question 10

Tioconazole

Answer 10

Has a basic azole found to a carbon with three other substituents to make four total. The four substituent makes the carbon a stereo centre which we want to avoid.

Question 11

What happened after tioconazole

Answer 11

Another nitrogen was added into the five membered ring and this was symmetrical on the other side and so there was only three substituents which removed the stereo Centre but the chlorine on the bottom aromatic ring had toxic side-effects when the chlorine was metabolised

Question 12

Fluconazole

Answer 12

Add two symmetrical azoles with an additional nitrogen bound and the aromatic ring at the bottom had two flooring molecules instead of chlorine

Question 13

Polyenes

Answer 13

Natural products that are isolated and also interfere with cell membrane

They have a hydrophilic alkene chain and a polar chain as well as a sugar

They insert themselves into the membrane and the two polar ends of the two polyenes bind and the hydrophobic end binds to the hydrophobic cell membrane tail

Question 14

Ergosterol and polynes

Answer 14

The OH group of the ergosterol interact with the sugar of the polyene

Question 15

Polyenes dont
Polyenes do

Answer 15

Interact with cholesterol
Make fungal cell membrane leaky

Question 16

What was the first synthetic antibiotic?

Answer 16

Prontosil

Question 17

Bacteriostatic

Answer 17

Stock bacterial cell growth

Question 18

Bacteriocidal

Answer 18

Kills bacteria

Question 19

Sulfolamides

Answer 19

Among the first antibiotics discovered and work by inhibiting the bacteria enzyme dihydropteoate synthase which is involved in the synthesis of folic acid and bacteria need folic acid to produce DNA and RNA as they cannot obtain it from their environment like humans do and this then disrupt their growth and replication and makes them bacteriostatic as they do not directly kill them

Question 20

Sulfonamides SAR

Answer 20

1.Aromatic Ring (Benzene Ring)
2.Sulfonamide Group (-SO₂-NH₂)
3.Substituent on the Aromatic Ring (R1)
4. Substituent on the Sulfonamide Nitrogen (R2