Ellagic acid, a polyphenolic compound synergistically interacts with concanamycin A, an inhibitor of Plasmodium falciparum proton pump

Ellagic acid is a bioactive phenolic constituent of many plants. Our previous study reported that ellagic acid alkalinised the Plasmodium falciparum digestive vacuole similarly to concanamycin A, a specific inhibitor of V-type H+-ATPase located on the membrane of the malaria parasite’s digestive vacuole. Therefore, this study aimed to determine the interaction of ellagic acid with concanamycin A by using the isobologram analysis of effects on parasite growth. A malarial SBYR Green I fluorescence-based (MSF) assay was conducted prior to the isobologram analysis to determine the antimalarial activity (IC50) of ellagic acid and concanamycin A. Six different combination solutions of the drugs were assigned based on their IC50 values and used in the isobologram analysis. The IC50 of ellagic acid and concanamycin A was 34.0 ± 0.18 nM and 9.2 ± 0.93 nM, respectively and the interaction of both drugs was found to be synergistic that could kill the parasites more effectively. This study suggests that ellagic acid and concanamycin A can be new candidates to be used in combination therapies with artemisinin, a standard antimalarial drug that has been postulated to affect the digestive vacuole pH.