Original Articles
Brandon Cullen1, Brian Henriks
Abstract
Synthetic ozonides (1,2,4-trioxolanes) are known to be effective antimalarials agents, and have been shown to have activity against lymphoma cells. In this study, conformational analysis was used on eight ozonides to see if the previously established pharmacophore would accurately predict the set’s activity against lymphoma cells. Based on previous work there are at least two crucial factors in anti-lymphoma activity, an ionizable amine and the distance from the proximal peroxide to the ionizable functional group. A small follow-up library of compounds was assayed for their activity. Seven of the compounds in the new library exhibited low activity and as a result the pharmacophore has been refined with two additional factors. Two alkyl groups alpha to the ionizable amine or a carbonyl beta to the ionizable amine interfered with the anti-lymphoma activity of the compounds in this set.