Simaomicin alpha: effects on the cell cycle of synchronized, cultured Plasmodium falciparum

Simaomicin alpha shows potent antimalarial activity in vitro and is known to be a cell-cycle effector. As erythrocytic schizogony of Plasmodium correlates with cell cycle events, we investigated the effect of simaomicin alpha on stage development of the malaria parasite Plasmodium falciparum. Simaomicin alpha interferes with normal parasite development in a time and concentration dependent manner. Parasites exposed to 2.5 nM simaomicin alpha at the ring stage or trophozoite stage showed disrupted development and immature schizont-like and segmenter-like forms were observed. However, schizont stage parasites were not affected by 2.5 nM simaomicin alpha. It is unclear whether mitosis involved in sequential parasite development occurred when parasites were exposed to simaomicin alpha at the ring or trophozoite stage. At a concentration of 5.0 nM, simaomicin alpha inhibited merozoite-trophozoite development. This concentration curtails p-LDH activity at all parasite stages, although its impact on the schizont stage is delayed for 24 hours.