In vitro leishmanicidal activity of benzophenanthridine alkaloids from Bocconia pearcei and related compounds

Leishmanicidal activities of benzophenanthridine alkaloids isolated from fruits of Bocconia pearcei and their derivatives were examined. Seven benzophenanthridine compounds were isolated from the methanolic extracts of B. pearcei. Among them, dihydrosanguinarine showed the most potent leishmanicidal activities (IC₅₀ value: 0.014 μg/ml, respectively). To examine the structure-activity relationship of the benzophenanthridine skeleton, the leishmanicidal activities for 32 synthetic samples were examined. The existence of bulky groups at the C₇-C₈ position was found to enhance the activity. On the other hand, the bulkiness at the C₂-C ₃ position on the D-ring, a carbonyl group at C-6, substitution at C-6 and cleavage or saturation of the C₅-C₆ bond reduced activity. A methyl group on nitrogen of the C-ring was thought to be necessary for significant activity.