ArticleACS chemical biology2016
Thiol-Activated HNO Release from a Ruthenium Antiangiogenesis Complex and HIF-1α Inhibition for Cancer Therapy.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 49 citations in OpenAlex.
- Nickel-Substituted Rubredoxin Undergoes Demetallation Upon Reaction With Nitric Oxide and Nitroxyl.Chembiochem : a European journal of chemical biology · 2026Article
- Electronic Modification of a Reduced Mononuclear Nonheme Iron Nitrosyl Complex Leads to HNO Release.Journal of the American Chemical Society · 2025Article
- Transition metals in angiogenesis - A narrative review.Materials today. Bio · 2023Review
- Unraveling Metal-Ligand Bonding in an HNO-Evolving {FeNO}Journal of the American Chemical Society · 2023Article
- New nitrosyl ruthenium complexes with combined activities for multiple cardiovascular disorders.Dalton transactions (Cambridge, England : 2003) · 2023Article
- A divergent mode of activation of a nitrosyl iron complex with unusual antiangiogenic activity.Journal of inorganic biochemistry · 2020Article
- An unusual bidentate methionine ruthenium(II) complex: photo-uncaging and antimicrobial activity.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Article
- [Ru(bpy)Frontiers in pharmacology · 2019Article
- Cysteine-activated hydrogen sulfide (HChemical communications (Cambridge, England) · 2018Article
- A vanillin-based copper(ii) metal complex with a DNA-mediated apoptotic activity.RSC advances · 2018Article
- Applications of Ruthenium Complex in Tumor Diagnosis and Therapy.Frontiers in pharmacology · 2018Review
- Is IQG-607 a Potential Metallodrug or Metallopro-Drug With a Defined Molecular Target inFrontiers in microbiology · 2018Review
- Bioresponsive cancer-targeted polysaccharide nanosystem to inhibit angiogenesis.International journal of nanomedicine · 2017Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Metallonitrosyl complexes are promising as nitric oxide (NO) donors for the treatment of cardiovascular, endothelial, and pathogenic diseases, as well as cancer. Recently, the reduced form of NO(-) (protonated as HNO, nitroxyl, azanone, isoelectronic with O2) has also emerged as a candidate for therapeutic applications including treatment of acute heart failure and alcoholism. Here, we show that HNO is a product of the reaction of the Ru(II) complex [Ru(bpy)2(SO3)(NO)](+) (1) with glutathione or N-acetyl-L-cysteine, using met-myoglobin and carboxy-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) as trapping agents. Characteristic absorption spectroscopic profiles for HNO reactions with met-myoglobin were obtained, as well as EPR evidence from carboxy-PTIO experiments. Importantly, the product HNO counteracted NO-induced as well as hypoxia-induced stabilization of the tumor-suppressor HIF-1α in cancer cells. The functional disruption of neovascularization by HNO produced by this metallonitrosyl complex was demonstrated in an in vitro angiogenesis model. This behavior is consistent with HNO biochemistry and contrasts with NO-mediated stabilization of HIF-1α. Together, these results demonstrate for the first time thiol-dependent production of HNO by a ruthenium complex and subsequent destabilization of HIF-1α. This work suggests that the complex warrants further investigation as a promising antiangiogenesis agent for the treatment of cancer.
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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.