ArticlePloS one2018
Discovery of indolylpiperazinylpyrimidines with dual-target profiles at adenosine A2A and dopamine D2 receptors for Parkinson's disease treatment.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 43 citations in OpenAlex.
- Indole Scaffolds in Neurological Therapeutics: Synthesis, Structure- Activity Relationships and Drug-Receptor Interactions.Mini reviews in medicinal chemistry · 2026Review
- Unraveling Neurodegenerative Disorders: The Potential of Indole and Imidazole-Based Heterocycles.Current topics in medicinal chemistry · 2026Review
- Machine Learning Approaches for Optimizing Drug Combinations in Neurodegenerative Diseases: A Brief Review.ACS omega · 2025Review
- Exploring Indole-Based Molecules as Novel Therapeutics for Parkinson's Disease: A Comprehensive Review.Mini reviews in medicinal chemistry · 2025Review
- Indole-Based Compounds in the Development of Anti-Neurodegenerative Agents.Molecules (Basel, Switzerland) · 2024Review
- Transcriptome profiling of five brain regions in a 6-hydroxydopamine rat model of Parkinson's disease.CNS neuroscience & therapeutics · 2021Article
- Arbutin effectively ameliorates the symptoms of Parkinson's disease: the role of adenosine receptors and cyclic adenosine monophosphate.Neural regeneration research · 2021Article
- Artificial intelligence to deep learning: machine intelligence approach for drug discovery.Molecular diversity · 2021Review
- Recent trends in artificial intelligence-driven identification and development of anti-neurodegenerative therapeutic agents.Molecular diversity · 2021Article
- Current Approaches and Tools Used in Drug Development against Parkinson's Disease.Biomolecules · 2021Review
- Artificial intelligence and machine learning-aided drug discovery in central nervous system diseases: State-of-the-arts and future directions.Medicinal research reviews · 2021Review
- Allosteric Interactions between Adenosine AInternational journal of molecular sciences · 2021Review
- Machine and deep learning approaches for cancer drug repurposing.Seminars in cancer biology · 2021Review
- Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency.Molecules (Basel, Switzerland) · 2020Article
- Long noncoding RNAs in neurodevelopment and Parkinson's disease.Animal models and experimental medicine · 2019Review
- Design, Synthesis and Evaluation of New Indolylpyrimidylpiperazines for Gastrointestinal Cancer Therapy.Molecules (Basel, Switzerland) · 2019Article
- The Rodent Models of Dyskinesia and Their Behavioral Assessment.Frontiers in neurology · 2019Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects. In this study, new chemical entities targeting both human A2A adenosine receptor and dopamine D2 receptor were designed and evaluated. Two computational methods, namely support vector machine (SVM) models and Tanimoto similarity-based clustering analysis, were integrated for the identification of compounds containing indole-piperazine-pyrimidine (IPP) scaffold. Subsequent synthesis and testing resulted in compounds 5 and 6, which acted as human A2A adenosine receptor binders in the radioligand competition assay (Ki = 8.7-11.2 μM) as well as human dopamine D2 receptor binders in the artificial cell membrane assay (EC50 = 22.5-40.2 μM). Moreover, compound 5 showed improvement in movement and mitigation of the loss of dopaminergic neurons in Drosophila models of PD. Furthermore, in vitro toxicity studies on compounds 5 and 6 did not reveal any mutagenicity (up to 100 μM), hepatotoxicity (up to 30 μM) or cardiotoxicity (up to 30 μM).
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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.