ArticlePharmaceutical research2023
Synthesis and Pharmacological Evaluation of Novel Triazole-Pyrimidine Hybrids as Potential Neuroprotective and Anti-neuroinflammatory Agents.
Article in Pharmaceutical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Recent Advances in Pyrimidine Molecular Hybrids, Green Synthetic Strategies, and Diverse Biological Applications.ACS omega · 2026Review
- Synthesis, antioxidant and antimicrobial activities, molecular docking study of new pyrimidine derivatives.Scientific reports · 2026Article
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- Drug Design for Cerebral Ischemia: A Molecular Perspective Review.CNS & neurological disorders drug targets · 2026Review
- Development of novel melatonin-isatin hybrids as multifunctional agents for Alzheimer's disease.Molecular diversity · 2025Article
- TargetingJournal of pharmaceutical analysis · 2025Article
- One-Pot Synthesis of Novel Pyrimidine Derivatives with Potential Antidiabetic Activity Through Dual α-Glucosidase and α-Amylase Inhibitors.Molecules (Basel, Switzerland) · 2025Article
- 4,6-Disubstituted pyrimidine-based microtubule affinity-regulating kinase 4 (MARK4) inhibitors: synthesis, characterization,Frontiers in pharmacology · 2024Article
- Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review.Antibiotics (Basel, Switzerland) · 2023Review
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveNeuroprotection is a precise target for the treatment of neurodegenerative diseases, ischemic stroke, and traumatic brain injury. Pyrimidine and its derivatives have been proven to use antiviral, anticancer, antioxidant, and antimicrobial activity prompting us to study the neuroprotection and anti-inflammatory activity of the triazole-pyrimidine hybrid on human microglia and neuronal cell model.
methodsA series of novel triazole-pyrimidine-based compounds were designed, synthesized and characterized by mass spectra, 1HNMR, 13CNMR, and a single X-Ray diffraction analysis. Further, the neuroprotective, anti-neuroinflammatory activity was evaluated by cell viability assay (MTT), Elisa, qRT-PCR, western blotting, and molecular docking.
resultsThe molecular results revealed that triazole-pyrimidine hybrid compounds have promising neuroprotective and anti-inflammatory properties. Among the 14 synthesized compounds, ZA3-ZA5, ZB2-ZB6, and intermediate S5 showed significant anti-neuroinflammatory properties through inhibition of nitric oxide (NO) and tumor necrosis factor-α (TNF-α) production in LPS-stimulated human microglia cells. From 14 compounds, six (ZA2 to ZA6 and intermediate S5) exhibited promising neuroprotective activity by reduced expression of the endoplasmic reticulum (ER) chaperone, BIP, and apoptosis marker cleaved caspase-3 in human neuronal cells. Also, a molecular docking study showed that lead compounds have favorable interaction with active residues of ATF4 and NF-kB proteins.
conclusionThe possible mechanism of action was observed through the inhibition of ER stress, apoptosis, and the NF-kB inflammatory pathway. Thus, our study strongly indicates that the novel scaffolds of triazole-pyrimidine-based compounds can potentially be developed as neuroprotective and anti-neuroinflammatory agents.
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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.