Studies For Structure Activity Relationship Of Anti-inflammatory (2E,2'E)-1,1'-(2-hydroxy-4,5,6-trimethoxy-1,3-phenylene) Bis (3-phenylprop-2-en-1-one) Derivatives

Chalcones have various therapeutic effects. A number of chalcone derivatives have been reported as anti-inflammatory agents and could reduce nitric oxide (NO) production by inhibition of inducible NOS protein synthase. The previously synthesized 2',4',6'-tris (methoxymethoxy) chalcone (TMMC) derivatives showed potent anti-inflammatory effects by inhibiting NO production in RAW 264.7 cells. Until now, people have made deep study of the pharmacological activity of chalcone, on this basis of that we are trying to design some more effective chalcone derivatives, namely existent of 2'-OH as well as twoα,β-unsaturated ketone group. A new series of (2E,2'E)-1,1'-(2-hydroxy-4,5,6-trimehoxy-1,3-phenylene)bis (3-phenylprop-2-en-l-one) derivatives that we designed using 3,4,5-trimethoxy phenol as the starting material, its anti-inflammatory effects via inhibition of nitric oxide production was analyzed. Some of compounds significantly showed inhibition of NO production. The 2'-OH group on the A ring elevates the electrophilicity with Michael addition of GSH and electron donating groups on the A ring stabilize the GSH adduct by decreasing the acidity of a-hydrogen. Strong electron donating groups on the B ring such as 4-dimethylamino group gave the weakest inhibition of NO production, possibly because it decreased the stability of the GSH adduct by weakening C-S bond.strength by moving the electron pair on nitrongen through an aromatic ring. The results show that the compound with dual chalcone display higher activities than that with one chalcone.