ArticleCNS & neurological disorders drug targets2026
Integrating Synthesis, Pharmacological Activity, and Molecular Modeling to Explore 1,2,4-Triazine Fused Thiazolidin-4-one Derivatives as GABA
Article in CNS & neurological disorders drug targets, 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
introductionEpilepsy is a common neurological disorder managed with anti-epileptic drugs (AEDs), which often cause side effects and limited efficacy. This study aims to evaluate a novel series of 1,2,4-triazine fused thiazolidin-4-one derivatives for their anticonvulsant and antioxidant potential as safer and more effective therapeutic options.
methodsTwelve 1,2,4-triazine fused thiazolidin-4-one derivatives (HRSP1-HRSP12) were synthesized. Anticonvulsant activity was assessed using the maximal electroshock (MES) model, while antioxidant potential was evaluated through DPPH and FRAP assays. Cortical GABA and glutamate levels were quantified in mice. Safety was evaluated via acute toxicity studies. In silico studies included molecular docking, induced fit docking, MM-GBSA, and molecular dynamics simulations to assess GABA
resultsHRSP8 showed the strongest anticonvulsant activity among the synthesized compounds, reducing hind limb tonic extension (HLTE) to 7.91 ± 0.25 s (30 mg/kg) and 6.89 ± 0.09 s (100 mg/kg), comparable to standard drugs (phenytoin and carbamazepine). It exhibited an ED DISCUSSION: HRSP8's effects appear to involve GABAA receptor modulation and neurochemical balance restoration, with additional antioxidant support. Its safety margin and stable receptor binding indicate therapeutic promise. These results align with existing GABAergic strategies in epilepsy. Further validation in chronic models and pharmacokinetic studies is needed.
conclusionHRSP8 demonstrated notable anticonvulsant and antioxidant activities, a wide safety margin, and strong affinity for the GABA
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