Quantum chemical analysis of structure-activity relationships in nonsteroidal anti-inflammatory drugs

EL Mehler, J Habicht and K Brune

Ab initio, quantum chemical methods are being used to analyze and interpret structure-activity relationships in nonsteroidal anti- inflammatory drugs. The biological data for this study derive from full dose-response curves of the inhibitory potency of phenols, salicylates, and benzoates on prostaglandin production in mouse macrophages. To date, about 80 compounds have been assayed and from this group a sample of 30 has been selected for calculation. The results show a correlation between the potency of the active compounds and the orbital energy of the highest occupied molecular orbital (HOMO) with a correlation coefficient of r approximately 0.8. These results indicate that potency increases with decreasing binding strength of the pi-HOMO electrons, suggesting that charge transfer may be important for interaction with specific or nonspecific binding sites.

Volume 22, Issue 3, pp. 525-528, 11/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics