Pathological investigation of neuroprotective activity of new derivatives of fused pyrazolyl-thienopyridines in Corazol-induced seizures

Abstract

Introduction. Seizures provoke several morphological alterations in the brain structures. These alterations are primarily located in the hippocampal CA1 region and the entorhinal cortex. Recurrent seizures are common in patients with epilepsy. Therapeutic options for this disease are very limited and most of them are aimed at relieving symptoms. In most cases, to treat epilepsy, anti-seizure drugs are used. Nevertheless, one-third of affected individuals have resistance to them. Thus, the study of new effective agents that can prevent epileptogenesis is still an ongoing challenge. In this work, we aimed to study the neuroprotective activity of several new derivatives of tricyclic pyrazolyl substituted thieno[2,3-c]isoquinolins (SHD-89 and SHD-91) and pyrano[4,3-d]thieno[2,3-b]pyridines (SHD-78 and SHD-85) as potential anti-seizure drugs. Materials and methods. The study was performed on mice (n=60). The action of compounds SHD-78, SHD-85, SHD-89, and SHD-91 was tested in seizures with and without Corazol administration. Histopathological examinations were performed in the hippocampus and the entorhinal cortex in different experimental groups. Results. The study showed that under the action of SHD-89 and SHD-78, there was a reduction in the number of neurons and activation of glial cells in examined regions of the brain. SHD-91 caused severe neurode-generative effects with changes in the brain structure. In contrast, under the action of SHD-85, the number of neurons was higher and with lower activation of glial cells. Conclusion. Studies showed that among the tested compounds SHD-85 possessed moderate neuroprotective activity and reduced gliosis and neuronal loss induced by Corazol. Keywords: anti-seizure drugs, pyrazolylthienopyridines, hippocampus, entorhinal cortex, histopathological examination