ArticleScientific reports2016
Discovery of novel PDE9 inhibitors capable of inhibiting Aβ aggregation as potential candidates for the treatment of Alzheimer's disease.
Article in Scientific reports, 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, 36 citations in OpenAlex.
- Dual-Site Acetylcholinesterase Inhibition and Multiscale Stability of Fused Quinoline Sulfonamides: A Chemoinformatic GA-MLR and Molecular Dynamics Study.International journal of molecular sciences · 2026Article
- Discovery of Effective Inhibitors Against Phosphodiesterase 9, a Potential Therapeutic Target of Alzheimer's Disease with Antioxidant Capacities.Antioxidants (Basel, Switzerland) · 2025Article
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- Different Inhibitors of Aβ42-Induced Toxicity Have Distinct Metal-Ion Dependency.ACS chemical neuroscience · 2020Article
- Drug Targets for Heart Failure with Preserved Ejection Fraction: A Mechanistic Approach and Review of Contemporary Clinical Trials.Annual review of pharmacology and toxicology · 2019Review
- Phosphodiesterase 9A in Brain Regulates cGMP Signaling Independent of Nitric-Oxide.Frontiers in neuroscience · 2019Article
- Discovery of novel PDE9A inhibitors with antioxidant activities for treatment of Alzheimer's disease.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Phosphodiesterase 9 (PDE9) regulates bovine tracheal smooth muscle relaxation.The Journal of veterinary medical science · 2018Article
- Advances in Multi-Functional Ligands and the Need for Metal-Related Pharmacology for the Management of Alzheimer Disease.Frontiers in pharmacology · 2018Review
- Phosphodiesterase type 5 and cancers: progress and challenges.Oncotarget · 2017Review
- Steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone: A convenient synthesis, antiproliferation activity, structure-activity relationships, and role of heterocyclic moiety.Scientific reports · 2017Article
- Alzheimer's Disease: The Role of Microglia in Brain Homeostasis and Proteopathy.Frontiers in neuroscience · 2017Review
- Selective inhibition of phosphodiesterases 4, 5 and 9 induces HSP20 phosphorylation and attenuates amyloid beta 1-42-mediated cytotoxicity.FEBS open bio · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, phosphodiesterase-9 (PDE9) inhibitors and biometal-chelators have received much attention as potential therapeutics for the treatment of Alzheimer's disease (AD). Here, we designed, synthesized, and evaluated a novel series of PDE9 inhibitors with the ability to chelate metal ions. The bioassay results showed that most of these molecules strongly inhibited PDE9 activity. Compound 16 showed an IC50 of 34 nM against PDE9 and more than 55-fold selectivity against other PDEs. In addition, this compound displayed remarkable metal-chelating capacity and a considerable ability to halt copper redox cycling. Notably, in comparison to the reference compound clioquinol, it inhibited metal-induced Aβ(1-42) aggregation more effectively and promoted greater disassembly of the highly structured Aβ fibrils generated through Cu(2+)-induced Aβ aggregation. These activities of 16, together with its favorable blood-brain barrier permeability, suggest that 16 may be a promising compound for treatment of AD.
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