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

Abstract

Background. 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. Methodology. 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. Results. 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. Conclusion. 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.