Abstract: AIM: The Seahorse XFe96 analyzer was used to evaluate the effects of thirteen types of international first-line antimalarial drugs in six categories on the mitochondrial electron transport chain (ETC) of Plasmodium falciparum  3D7 (P. falciparum 3D7). METHODS: The antimalarial activity of in vitro drugs acting on P. falciparum 3D7 was evaluated using the three-day inhibition method and SYBR Green I fluorescence analysis method. MACS technology was used to separate and purify P. falciparum 3D7. The mitochondrial oxygen consumption rate (OCR) of Seahorse XF analysis system was used to characterize the bioenergy of P. falciparum 3D7 mitochondria at different times to investigate the effects of antimalarial drugs on mitochondrial aerobic respiration of Plasmodium falciparum. RESULTS: The results of flow cytometry showed that the Plasmodium of trophozoite stages was enriched successfully. The results of in vitro antimalarial activity evaluation showed that, except for the antimalarial drug proguanil (Pro), the other twelve antimalarial drugs were all of the nmol/L level against P. falciparum 3D7. The results of the mitochondrial aerobic respiration showed that the five concentrations of dihydroartemisinin (DHA) and chloroquine (CQ) (0.4, 1, 5, 10, 50×IC50) on P. falciparum 3D7 mitochondria aerobic respiration had no significant effect. At the concentration of 5×IC50 for thirteen antimalarial drugs, Artemisinin (ART), arteether (ARE) and artemether (ARM) can significantly increase mitochondrial maximum respiration, Quinine (QN) and Pro only had a decoupling effect on the oxidative phosphorylation of mitochondrial ETC of P. falciparum 3D7, which did not completely destroy the function of mitochondrial ETC. Atovaquone (Ato) had a significant inhibitory effect on P. falciparum 3D7 mitochondrial aerobic respiration, significantly decrease mitochondrial maximum respiration and proton leak, completely destroying the function of mitochondrial ETC, and the remaining ten antimalarial drugs had no significant effect on P. falciparum 3D7 mitochondrial aerobic respiration. CONCLUSION: The target of most antimalarial drugs in thirteen antimalarial drugs is not the ETC pathway of Plasmodium mitochondrial aerobic respiration.

Key words: antimalarial drugs, Plasmodium falciparum, mitochondria, aerobic respiration, Seahorse XFe96