The isobenzofuran-1(3H)-ones (phthalides) exhibit various biological activities, including antioxidant activity on reactive oxygen species (ROS). An excess of ROS that cannot be naturally contained by cellular enzymatic systems is called redox imbalance, which damage cell membranes, proteins, and DNA, thereby possibly triggering neuronal death in several neurodegenerative diseases. Considering our ongoing efforts to find useful compounds to control redox imbalance, herein we evaluated the antioxidant activity of two phtalides (compounds 3 and 4), using primary cultures of hippocampal neurons. Spectrophotometric assays showed that compound 3 significantly reduced (p ≤ 0.05) ROS levels and lipid peroxidation compared to the control treatment, while compound 4 was unable at any of the tested concentrations. Despite their structural similarity, these compounds behave differently in the intracellular environment, which was reliably corroborated by the determination of oxidation potentials via cyclic voltammetry. It was demonstrated that compound 3 presents a lower oxidation potential. The combination of the mentioned methods allowed us to find a strong correlation between the chemical structure of compounds and their biological effects. Taking together, the results indicate that compound 3 presents desirable characteristics to act as a candidate pharmacological agent for use in the prevention and treatment of neurodegenerative diseases.

异苯并呋喃-1（3 H）-ones（phthalides）具有多种生物学活性，包括对活性氧（ROS）的抗氧化活性。细胞酶系统无法自然包含的过量ROS被称为氧化还原失衡，它会破坏细胞膜，蛋白质和DNA，从而可能触发几种神经退行性疾病中的神经元死亡。考虑到我们不断努力寻找有用的化合物来控制氧化还原失衡，在此我们使用海马神经元原代培养物评估了两种邻苯二甲酸酯（化合物3和4）的抗氧化活性。分光光度法测定表明化合物3显着还原（p ≤0.05）ROS水平和脂质过氧化与对照处理相比，而化合物4在任何测试浓度下均无法。尽管它们的结构相似，但这些化合物在细胞内环境中的行为却有所不同，通过循环伏安法测定氧化电位可以可靠地证实这些化合物。已证明化合物3具有较低的氧化电位。上述方法的结合使我们能够找到化合物的化学结构与其生物学效应之间的强相关性。综合起来，结果表明化合物3 呈现出期望的特征，以充当用于预防和治疗神经退行性疾病的候选药理剂。