Identification of a potent and selective gametocytocidal antimalarial agent from the stem barks of Lophira lanceolata

Bioassay-guided fractionation of the organic extract obtained from stem barks of the African plant Lophira lanceolata has led to the isolation of seven biflavonoids, including the new α′-chlorolophirone E (5) and 5′-chlorolophirone D (6). Among the isolated compounds, the bichalcone lophirone E was identified as a potent gametocytocidal agent with an IC50 value in the nanomolar range and negligible cytotoxicity (selectivity index = 570). Lophirone E proved to be about 100 times more active against P. falciparum stage V gametocytes than on asexual blood stages, thus exhibiting a unique stage-specific activity profile. The isolation of structural analogues allowed to draw preliminary structure-activity relationships, identifying the critical positions on the chemical scaffold of lophirone E.