Is Aspirin a non-selective or selective COX Inhibitor?
Aspirin is a non-selective competitive COX inhibitor - an NSAID
How does aspirin inhibit COX enzyme?
Aspirin covalentlybind to a serine residue that is close to heme that the acylationcauses a stericblock. The heme cannot be accessed by the substrate (arachidonic acid) => the enzyme is rendered inactive
What type of interaction do non-selective NSAIDs have with Arg120?
What are the key structural features of non-selective NSAIDs?
Restricted planar: steric bulk, blocking the arachidonic acid from entering thy hydrophobic channel to access the heme active site within COX enzyme. Eg: aromatic substituent - benzene ring
Acidicgroup: form ionic interaction with Arg 120. Eg: Carboxylic acid, COOH - is deprotonated at physiological Ph to form carboxylate
Lipophilicgroup: Eg: phenol, OH => high degree of lipophilicity
What are general characteristics of COX-2 selective NSAIDs?
have an additional hydrophilic binding site e.g sulfones or sulphonamide
Any 5 or 6membered ring => larger molecule with restricted conformational freedom