Anti-Inflammatory Agents; IV. Structure Activity Relationships of Sesquiterpene Lactone Esters Derived from Helenalin

Abstract

Helenalin mono- and di-functional esters were found to posses potent anti-inflammatory action in rodents. The most effective dose for the helenalin esters was 2.5 mg/kg × 2 for the inhibition of inflammation while the writhing reflex followed a dose response effect. There appeared to be no evidence that the presence of the ester function significantly increased the activity of the helenalin derivatives as anti-inflammatory agents. This study did demonstrate that the free 6-hydroxy group of helenalin was not necessary for activity as an ester function could be formed from the 6-hydroxy group while still retaining good activity. From the di-functional esters, the bis[helenalinyl] adipate derivative proved to be slightly more active than helenalin at the same dose in both screens. Generally, the monofunctional esters were less active than the di-functional esters and the parent agent, helenalin. Helenalinyl m-chlorocinnamate was found to be the most active of the monofunctional esters as an anti-inflammatory agent.