Chelucci Rafael Consolin, Chiquetto Richard, Chiba Diego Eidy, Scarim Cauê Benito, Chin Chung Man, Dos Santos Jean Leandro
São Paulo State University - UNESP, School of Pharmaceutical Sciences, Araraquara, São Paulo, Brazil.
Med Chem. 2025 Jan 9. doi: 10.2174/0115734064336758241113180402.
Epilepsy encompasses numerous syndromes characterized by spontaneous, intermittent, and abnormal electrical activity in the brain. Affecting about 1-2% of the population, it is estimated that approximately 30-40% of patients experience refractory epilepsy, which does not respond to traditional anticonvulsant drugs.
Therefore, developing novel, safe, and effective antiepileptic drugs remains a medical need. In this study, we synthesized a series of isoindoline-1,3-dione derivatives and evaluated their anticonvulsant effects.
Compounds (2a-j) and (5) were obtained with yields ranging from 52-97%. These compounds were assessed for their protective effects on the following parameters: a) time to first seizure (seizure latency), b) seizure duration, and c) mortality rate post-seizure. The most active compound, (2a), increased seizure latency, reduced seizure duration, and lowered the mortality rate.
These findings indicate that compound (2a) is a promising new anticonvulsant prototype, offering an alternative to current anticonvulsant drugs.
癫痫包括许多综合征,其特征是大脑中出现自发、间歇性和异常的电活动。据估计,癫痫影响着约1%-2%的人口,约30%-40%的患者患有难治性癫痫,对传统抗惊厥药物无反应。
因此,开发新型、安全且有效的抗癫痫药物仍然是医学上的需求。在本研究中,我们合成了一系列异吲哚啉-1,3-二酮衍生物并评估了它们的抗惊厥作用。
得到了化合物(2a-j)和(5),产率在52%-97%之间。评估了这些化合物对以下参数的保护作用:a)首次发作时间(发作潜伏期),b)发作持续时间,以及c)发作后的死亡率。活性最高的化合物(2a)延长了发作潜伏期,缩短了发作持续时间,并降低了死亡率。
这些发现表明化合物(2a)是一种有前景的新型抗癫痫原型药物,为当前的抗癫痫药物提供了一种替代选择。