Extracts Obtained from Pterocarpus angolensis DC and Ziziphus mucronata Exhibit Antiplasmodial Activity and Inhibit Heat Shock Protein 70 (Hsp70) Function.

Natasha Potgieter,Heinrich Hoppe,Afsatou Traoré,Addmore Shonhai,Chinedu Anokwuru,Isaiah Ramaite,Muendi Sigidi,Tawanda Zininga,Milingoni Tshisikhawe

doi:10.3390/molecules22081224

Natasha Potgieter, Heinrich Hoppe + Show 7 more

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https://doi.org/10.3390/molecules22081224

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Abstract

Malaria parasites are increasingly becoming resistant to currently used antimalarial therapies, therefore there is an urgent need to expand the arsenal of alternative antimalarial drugs. In addition, it is also important to identify novel antimalarial drug targets. In the current study, extracts of two plants, Pterocarpus angolensis and Ziziphus mucronata were obtained and their antimalarial functions were investigated. Furthermore, we explored the capability of the extracts to inhibit Plasmodium falciparum heat shock protein 70 (Hsp70) function. Heat shock protein 70 (Hsp70) are molecular chaperones whose function is to facilitate protein folding. Plasmodium falciparum the main agent of malaria, expresses two cytosol-localized Hsp70s: PfHsp70-1 and PfHsp70-z. The PfHsp70-z has been reported to be essential for parasite survival, while inhibition of PfHsp70-1 function leads to parasite death. Hence both PfHsp70-1 and PfHsp70-z are potential antimalarial drug targets. Extracts of P. angolensis and Z. mucronata inhibited the basal ATPase and chaperone functions of the two parasite Hsp70s. Furthermore, fractions of P. angolensis and Z. mucronata inhibited P. falciparum 3D7 parasite growth in vitro. The extracts obtained in the current study exhibited antiplasmodial activity as they killed P. falciparum parasites maintained in vitro. In addition, the findings further suggest that some of the compounds in P. angolensis and Z. mucronata may target parasite Hsp70 function.

Highlights

Malaria remains a major killer disease with devastating outcomes, in children and pregnant mothers
We previously reported that PfHsp70-1 interacts with PfHsp70-z, and for this reason we think that PfHsp70-z acts as an independent molecular chaperone and may serve as a nucleotide exchange factors (NEF) for PfHsp70-1 [13]
We investigated the effects of the P. angolensis and Z. mucronata extracts on the functional features of both PfHsp70-1 and PfHsp70-z

Summary

Introduction

Malaria remains a major killer disease with devastating outcomes, in children and pregnant mothers. Currently malaria is a treatable disease, it is of concern that the population of parasites that are resistant to the most reliable antimalarial treatment (artemisinin-based combination therapies) is growing [1]. It is against this background that it is important to search for alternative effective antimalarial drugs. It is important to identify novel antimalarial drug targets. Heat shock proteins (Hsps) are molecules that facilitate protein folding (molecular chaperones) [2]. The Hsp members constitute one of the most ubiquitous molecular chaperone families.

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