ArticleCurrent topics in medicinal chemistry2026
Design, Synthesis and Anti-Alzheimer's Activity of Some Hybrid Molecule of Oxymatrine Through TGF-β.
Article in Current topics in medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimsThis study aimed to investigate novel therapeutic approaches for Alzheimer's disease (AD) by targeting the Transforming Growth Factor-β (TGF-β) pathway using hybrid compounds derived from oxymatrine and amino acids.
backgroundAD remains a significant challenge in neurodegenerative disorders, necessitating innovative treatments that can mitigate its devastating effects. The TGF-β pathway has been implicated in AD pathogenesis, making it a promising target for therapeutic intervention.
objectiveThe objective of this study was to synthesize and evaluate the anti-AD activity of hybrid molecules combining oxymatrine with different amino acids. These compounds were designed to enhance blood-brain barrier permeability and selectively modulate TGF-β signaling.
methodsHybrid compounds were synthesized based on molecular docking studies. Characterization of synthesized compounds was performed using thin-layer chromatography (TLC), infrared spectroscopy (IR), and nuclear magnetic resonance (NMR) spectroscopy. Anti-AD activity was assessed using an AD rat model induced by a high-cholesterol diet, employing behavioral tests (radial arm maze and Hebb's Williams maze) and biochemical assays to measure Aβ and TGF-β levels.
resultsAll hybrid molecules exhibited significant anti-AD activity, with compound 3B demonstrating the highest efficacy at a dose of 100 mg/kg. Biochemical analyses revealed modulation of Aβ and TGF-β levels, indicating the compounds' potential therapeutic effects against AD.
conclusionThis study unveils a new class of hybrid compounds derived from oxymatrine and amino acids that effectively target the TGF-β pathway, offering promising therapeutic potential for AD. These compounds demonstrate neuroprotective properties, suggesting they may mitigate ADrelated pathology, including tau deposition, synaptic dysfunction, and cognitive decline.
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