α-Lipoic acid (LA), a dithiol micronutrient, acts as a vital cofactor in various cellular catabolic reactions and is also known as a universal antioxidant. The therapeutic efficacy of LA is compromised by a poor aqueous solubility as well as a short half-life. In the present study, LA was conjugated to d-α-tocopherol polyethylene glycol succinate (TPGS) using carbodiimideacid–alcohol coupling reaction. The synthesized conjugate (TPGS-LA) was characterized using ¹H and ¹³C nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR), UV–vis spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The TPGS-LA conjugate was demonstrated to be biocompatible and to have better anticonvulsion activity as compared to native LA in pentylenetetrazol (PTZ)-induced convulsions in zebrafish. Moreover, zebrafish larvae pretreated with TPGS-LA conjugate demonstrated a significant (p < 0.05) reduction of protein carbonylation levels and downregulation of c-fos expression during seizures as compared to native LA. Conclusively, the present findings demonstrate that the TPGS-LA conjugate can be a promising approach for the delivery of LA.

中文翻译：

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R-α-硫辛酸与 d-α-生育酚聚乙二醇 1000 琥珀酸酯共轭：合成、表征和对抗癫痫活性的影响

α-硫辛酸 (LA) 是一种二硫醇微量营养素，是各种细胞分解代谢反应中的重要辅助因子，也被称为通用抗氧化剂。LA 的治疗功效受到水溶性差和半衰期短的影响。在本研究中，LA 使用碳二亚胺酸-醇偶联反应与d -α-生育酚聚乙二醇琥珀酸酯 (TPGS) 偶联。使用¹ H 和^{13表征合成的偶联物 (TPGS-LA)}C 核磁共振 (NMR)、傅里叶变换红外光谱 (FT-IR)、紫外-可见光谱和基质辅助激光解吸/电离飞行时间质谱 (MALDI-TOF MS)。在戊四唑 (PTZ) 诱导的斑马鱼惊厥中，与天然 LA 相比，TPGS-LA 缀合物被证明具有生物相容性并具有更好的抗惊厥活性。此外，与天然 LA 相比，用 TPGS-LA 缀合物预处理的斑马鱼幼虫在癫痫发作期间表现出显着 ( p < 0.05) 降低蛋白质羰基化水平和下调c-fos表达。总之，目前的研究结果表明，TPGS-LA 偶联物可能是一种有前途的 LA 递送方法。