Acanthospermum australe Extract Inhibits the Chaperone Activity of Plasmodium falciparum Heat Shock Protein 70-1

Abstract

The resistance of malaria parasites towards the current antimalarial therapies continues to fuel the search for new antimalarial drugs, preferably from natural sources. This study aimed to investigate the potential of the dichloromethane extract of <i>Acanthospermum australe</i> to inhibit <i>Plasmodium falciparum</i> heat shock protein 70-1 (<i>Pf</i>Hsp70-1). The plasmodium lactate dehydrogenase (pLDH) assay was used to determine the antiplasmodial activity of the crude extract against the chloroquine-sensitive <i>P. falciparum</i> strain 3D7. The inhibitory effect of the plant extract on the chaperone activity of <i>P. falciparum</i> heat shock protein 70-1 (<i>Pf</i>Hsp70-1) was determined using the ATPase, thermally induced luciferase and malate dehydrogenase (MDH) assays. The extract showed a significantly high activity against <i>P. falciparum</i> strain 3D7 with an IC₅₀ value of 1.3 µg/mL. A decrease in thermally induced aggregation of MDH and luciferase was observed when each of the proteins was incubated with <i>Pf</i>Hsp70-1 only. However, an increased protein aggregation was observed when the proteins were incubated with <i>Pf</i>Hsp70-1 in the presence of the plant extract. The extract also exhibited inhibitory activity on the ATPase activity of <i>Pf</i>Hsp70-1. The results obtained from this study suggest that <i>A. australe</i> extract contains compounds that could target malaria parasite Hsp70 functions.