ArticlePloS one2013
A purine analog synergizes with chloroquine (CQ) by targeting Plasmodium falciparum Hsp90 (PfHsp90).
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Malaria Public Health Status: Global Context and Update on Gulf Cooperation Council Countries.Advances in experimental medicine and biology · 2026Review
- Article
- Investigation of a cryptic ligand binding site on Plasmodium falciparum Hsp90.Bioorganic & medicinal chemistry · 2025Article
- Biochemistry of Heat Shock Proteins From Human Intracellular Protozoan Parasites as Diagnostic and Therapeutic Biomarkers.Biochemistry · 2025Review
- Characterization and Inhibition of the Chaperone Function of Plasmodium falciparum Glucose-Regulated Protein 94 kDa (Pf Grp94).Proteins · 2025Article
- The possibilities and challenges associated with selective targetingTransactions of the Royal Society of South Africa. Royal Society of South Africa · 2025Article
- Ursolic acid acetate and iso-mukaadial acetate bind to Plasmodium falciparum Hsp90, abrogating its chaperone function in vitro.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Selective targeting of Plasmodium falciparum Hsp90 disrupts the 26S proteasome.Cell chemical biology · 2024Article
- Article
- In silico prediction and in vitro assessment of novel heterocyclics with antimalarial activity.Parasitology research · 2023Article
- Pharmacophore Model-Based Virtual Screening Workflow for Discovery of Inhibitors TargetingACS omega · 2023Article
- Structural Basis of Parasitic HSP90 ATPase Inhibition by Small Molecules.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Structural Characterization of Human Heat Shock Protein 90 N-Terminal Domain and Its Variants K112R and K112A in Complex with a Potent 1,2,3-Triazole-Based Inhibitor.International journal of molecular sciences · 2022Article
- Neurotransmitters and molecular chaperones interactions in cerebral malaria: Is there a missing link?Frontiers in molecular biosciences · 2022Review
- Inhibitors of theCells · 2021Review
- Partners in Mischief: Functional Networks of Heat Shock Proteins ofBiomolecules · 2019Review
- Identification and characterization of the antiplasmodial activity of Hsp90 inhibitors.Malaria journal · 2017Article
- Low concentration of chloroquine enhanced efficacy of cisplatin in the treatment of human ovarian cancer dependent on autophagy.American journal of translational research · 2017Article
- In vitro and in vivo anti-malarial activity of novel harmine-analog heat shock protein 90 inhibitors: a possible partner for artemisinin.Malaria journal · 2016Article
- Plasmodium falciparum Hsp70-z, an Hsp110 homologue, exhibits independent chaperone activity and interacts with Hsp70-1 in a nucleotide-dependent fashion.Cell stress & chaperones · 2016Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundDrug resistance, absence of an effective vaccine, and inadequate public health measures are major impediments to controlling Plasmodium falciparum malaria worldwide. The development of antimalarials to which resistance is less likely is paramount. To this end, we have exploited the chaperone function of P. falciparum Hsp90 (PfHsp90) that serves to facilitate the expression of resistance determinants.
methodsThe affinity and activity of a purine analogue Hsp90 inhibitor (PU-H71) on PfHsp90 was determined using surface plasmon resonance (SPR) studies and an ATPase activity assay, respectively. In vitro, antimalarial activity was quantified using flow cytometry. Interactors of PfHsp90 were determined by LC-MS/MS. In vivo studies were conducted using the Plasmodium berghei infection mouse model.
resultsPU-H71 exhibited antimalarial activity in the nanomolar range, displayed synergistic activity with chloroquine in vitro. Affinity studies reveal that the PfHsp90 interacts either directly or indirectly with the P. falciparum chloroquine resistance transporter (PfCRT) responsible for chloroquine resistance. PU-H71 synergized with chloroquine in the P.berghei mouse model of malaria to reduce parasitemia and improve survival.
conclusionsWe propose that the interaction of PfHsp90 with PfCRT may account for the observed antimalarial synergy and that PU-H71 is an effective adjunct for combination therapy.
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