Medicinally Active Carboxylic Derivatives

Question 1

Enzyme Inhibition Outline

Answer 1

Drugs interact with amino acid at binding site to form a covalent bond.

Question 2

Aspirin Mode of Action

Answer 2

Inhibits prostaglandin-H2-synthase-cyclooxygenase . Reacts with serine (with OH group) at active site

Question 3

Aspirin Chemical equation

Answer 3

Ester (aspirin) + alcohol (serine on active site) -> ester (modified active site) + phenol (salicylic acid)

Question 4

Penicillin Mode of Action

Answer 4

Inhibits glycopeptide transpeptidase. Reacts with serine on active site

Question 5

Penicillin Reaction

Answer 5

Lactam (penicillin) + alcohol (serine) -> ester + amine

Question 6

Prostaglandin-H2-Synthase Outline

Answer 6

Coverts arachidonic acid to prostaglandins and thromboxanes. Inhibition of COX active site (not POX) relieves fever and pain. Side effects: nephrotoxicity and gastric mucosa irritation

Question 7

Prostaglandins Def

Answer 7

Hormones at low concs in body control pain, fever and inflammation

Question 8

Aspirin Outline

Answer 8

NSAID. Inhibits cyclooxygenase

Question 9

Arachidonic acid and COX

Answer 9

Interacts Arg 119 +NH and -O on arachidonic acid interact and convert to prostaglandins. Nucleophilic substitution: serine (OH) = nucleophile, CH3CO (on aspirin) = electrophile and rest of aspirin (ester) = leaving group

Question 10

How is the COX receptor inhibited

Answer 10

Sterically. Due to acetylation at active site, which is irreversible

Question 11

COX 2 function

Answer 11

Inflammation regulation. Bigger active site (by 1 C). Make drugs selective by making them on the bigger side

Question 12

Cox 1 Function

Answer 12

Gastric secretion. Smaller active site (smaller by 1 C)

Question 13

Selective inhibitor of COX2

Answer 13

Celecoxib. Sulfonimade group fits into active site. Doesn’t fit into COX 1 active site (isoleucine)

Question 14

Beta Lactam Ring Outline

Answer 14

3 Cs and N in a ring. C and N is an amide bond (lactam). One C has a double O bond. Bond angles are 90 degrees (square). Very strained = very reactive. N to CO (amide bond) is the weakest bond

Question 15

Action of beta lactamase

Answer 15

Breaks amide bond.

Question 16

Why can’t lactam react with alcohol

Answer 16

NH2 is a poor leaving group

Question 17

Bi-cyclic penicillin core

Answer 17

2 fused ring. Open book

Question 18

Angles of highly strained beta lactam ring

Answer 18

109 degrees

Question 19

Why do beta lactams not have resonance structures

Answer 19

Double bonds are too physically unstable in beta lactam rings to exist

Question 20

Best leaving group

Answer 20

Cl-

Question 21

Worst leaving group

Answer 21

C-R1R2R3