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

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...

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Published in:Molecules (Basel, Switzerland) Switzerland), 2017-08, Vol.22 (8), p.1224
Main Authors: Zininga, Tawanda, Anokwuru, Chinedu P, Sigidi, Muendi T, Tshisikhawe, Milingoni P, Ramaite, Isaiah I D, Traoré, Afsatou N, Hoppe, Heinrich, Shonhai, Addmore, Potgieter, Natasha
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - antagonists & inhibitors
Antimalarials - chemistry
Antimalarials - pharmacology
Dose-Response Relationship, Drug
HSP70 Heat-Shock Proteins - antagonists & inhibitors
Phenols - chemistry
Phenols - pharmacology
Plant Extracts - chemistry
Plant Extracts - pharmacology
Plasmodium - drug effects
Plasmodium falciparum - drug effects
Plasmodium falciparum - growth & development
Protein Binding
Protein Stability - drug effects
Pterocarpus - chemistry
Ziziphus - chemistry
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Summary: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, and were obtained and their antimalarial functions were investigated. Furthermore, we explored the capability of the extracts to inhibit heat shock protein 70 (Hsp70) function. Heat shock protein 70 (Hsp70) are molecular chaperones whose function is to facilitate protein folding. 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 and inhibited the basal ATPase and chaperone functions of the two parasite Hsp70s. Furthermore, fractions of and inhibited 3D7 parasite growth in vitro. The extracts obtained in the current study exhibited antiplasmodial activity as they killed parasites maintained in vitro. In addition, the findings further suggest that some of the compounds in and may target parasite Hsp70 function.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules22071224