Relaxant effects of quercetin methyl ether derivatives in isolated guinea pig trachea and their structure-activity relationships

In the present study, we attempted to compare quercetin methyl ethers and t o look for the structure-activity relationships, which may be helpful for s ynthesizing more active compounds for the treatment of asthma. Four present and two previously studied quercetin methyl ethers concentration-dependent ly relaxed histamine (30 mu M), carbachol (0.2 mu M) and KCl (30 mM) induce d precontraction. According to their IC25 values to histamine-induced preco ntraction, the potency order was quercetin 3,3',4',5,7-pentamethyl ether (Q PME), quercetin 3-methyl ether > quercetin, quercetin 3,4',7-trimethyl ethe r (ayanin) > quercetin 4'-methyl ether (tamarixetin), quercetin 3,3',4',7,- tetramethyl ether (QTME). Therefore, the methylation at 3, at 5, and at bot h 3 and 7 positions of the A or/and C ring of quercetin nucleus may increas e their tracheal relaxant activity. However, the methylation at the 3' and at the 4' position of the B ring of quercetin nucleus may decrease their tr acheal relaxant activity.