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从安哥拉紫檀和尖叶枣中提取的提取物具有抗疟活性并抑制热休克蛋白70(Hsp70)的功能。

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

作者信息

Zininga Tawanda, Anokwuru Chinedu P, Sigidi Muendi T, Tshisikhawe Milingoni P, Ramaite Isaiah I D, Traoré Afsatou N, Hoppe Heinrich, Shonhai Addmore, Potgieter Natasha

机构信息

Biochemistry Department, School of Mathematical and Natural Sciences, University of Venda, Private Bag X5050, 0950 Thohoyandou, South Africa.

Chemistry Department, School of Mathematical and Natural Sciences, University of Venda, Private Bag X5050, 0950 Thohoyandou, South Africa.

出版信息

Molecules. 2017 Jul 28;22(8):1224. doi: 10.3390/molecules22081224.

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, 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.

摘要

疟原虫对目前使用的抗疟疗法的耐药性日益增强,因此迫切需要扩充替代抗疟药物的种类。此外,确定新的抗疟药物靶点也很重要。在本研究中,获取了两种植物的提取物,并对其抗疟功能进行了研究。此外,我们还探究了这些提取物抑制热休克蛋白70(Hsp70)功能的能力。热休克蛋白70(Hsp70)是分子伴侣,其功能是促进蛋白质折叠。疟原虫的主要病原体疟原虫表达两种定位于胞质溶胶的Hsp70:PfHsp70-1和PfHsp70-z。据报道,PfHsp70-z对疟原虫的存活至关重要,而抑制PfHsp70-1的功能会导致疟原虫死亡。因此,PfHsp70-1和PfHsp70-z都是潜在的抗疟药物靶点。两种植物的提取物抑制了两种疟原虫Hsp70的基础ATP酶和分子伴侣功能。此外,两种植物的组分在体外抑制了3D7疟原虫的生长。本研究中获得的提取物表现出抗疟活性,因为它们杀死了体外培养的疟原虫。此外,研究结果进一步表明,两种植物中的一些化合物可能靶向疟原虫的Hsp70功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b5a/6152082/40e6f41e4151/molecules-22-01224-g001.jpg

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