ArticlePloS one2012
17-AAG kills intracellular Leishmania amazonensis while reducing inflammatory responses in infected macrophages.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Development of a 17-DMAG-Loaded Carboxymethylcellulose Gel forACS omega · 2026Article
- The anti-aging potential of VA'S new derivatives through metabolomic profiling.Scientific reports · 2025Article
- Salivary proteins modulate Candida albicans virulence and may prevent oropharingeal candidiasis.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024Article
- Intraperitoneal Administration of 17-DMAG as an Effective Treatment againstPathogens (Basel, Switzerland) · 2024Article
- Pharmacokinetics, Dose-Proportionality, and Tolerability of Intravenous Tanespimycin (17-AAG) in Single and Multiple Doses in Dogs: A Potential Novel Treatment for Canine Visceral Leishmaniasis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Anti-inflammatory activities of novel heat shock protein 90 isoform selective inhibitors in BV-2 microglial cells.Frontiers in molecular biosciences · 2024Article
- Systems biology of autophagy in leishmanial infection and its diverse role in precision medicine.Frontiers in molecular biosciences · 2023Review
- Autophagy in protists and their hosts: When, how and why?Autophagy reports · 2023Article
- Structural Basis of Parasitic HSP90 ATPase Inhibition by Small Molecules.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Effects of negative air ions (NAIs) on Leishmania major: A novel tool for treatment of zoonotic cutaneous leishmaniasis (ZCL).PloS one · 2022Article
- 17-AAG-Induced Activation of the Autophagic Pathway inMicroorganisms · 2021Article
- Quantitative Proteomics Reveals that Hsp90 Inhibition Dynamically Regulates Global Protein Synthesis in Leishmania mexicana.mSystems · 2021Article
- Heat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils.Infection and immunity · 2021Review
- Design, Synthesis and In Vitro Investigation of Novel Basic Celastrol Carboxamides as Bio-Inspired Leishmanicidal Agents Endowed with Inhibitory Activity againstBiomolecules · 2021Article
- Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During theFrontiers in cell and developmental biology · 2021Article
- Development and Characterization of PLGA Nanoparticles Containing 17-DMAG, an Hsp90 Inhibitor.Frontiers in chemistry · 2021Article
- A docking-based structural analysis of geldanamycin-derived inhibitor binding to human or Leishmania Hsp90.Scientific reports · 2019Article
- Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed,Frontiers in cellular and infection microbiology · 2018Article
- In Search of Biomarkers for Pathogenesis and Control of Leishmaniasis by Global Analyses ofFrontiers in cellular and infection microbiology · 2018Review
- Characterization of HSP90 isoforms in transformed bovine leukocytes infected with Theileria annulata.Cellular microbiology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLeishmaniasis is a neglected endemic disease with a broad spectrum of clinical manifestations. Pentavalent antimonials have been the treatment of choice for the past 70 years and, due to the emergence of resistant cases, the efficacy of these drugs has come under scrutiny. Second-line drugs are less efficacious, cause a range of side effects and can be costly. The formulation of new generations of drugs, especially in developing countries, has become mandatory. METHODOLOGY/PRINCIPAL
findingsWe investigated the anti-leishmanial effect of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an HSP90 inhibitor, in vitro. This inhibitor is currently in clinical trials for cancer treatment; however, its effects against intracellular Leishmania remain untested. Macrophages infected with L. amazonensis were treated with 17-AAG (25-500 nM) and parasite load was quantified using optical microscopy. Parasite load declined in 17-AAG-treated macrophages in a dose- and time-dependent manner. Intracellular parasite death became irreversible after 4 h of treatment with 17-AAG, and occurred independent of nitric oxide (NO) and superoxide (O(2) (-)) production. Additionally, intracellular parasite viability was severely reduced after 48 h of treatment. Interestingly, treatment with 17-AAG reduced pro-inflammatory mediator production, including TNF-α, IL-6 and MCP-1, yet IL-12 remained unaffected. Electron microscopy revealed morphological alterations, such as double-membrane vacuoles and myelin figures at 24 and 48 h after 17-AAG treatment. CONCLUSIONS/SIGNIFICANCE: The HSP90 inhibitor, 17-AAG, possesses high potency under low dosage and reduces both pro-inflammatory and oxidative molecule production. Therefore, further studies are warranted to investigate this inhibitor's potential in the development of new generations of anti-leishmanials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.