Synthesis, antiepileptic effects, and structure-activity relationships of α-asarone derivatives: In vitro and in vivo neuroprotective effect of selected derivatives

• Published in: Bioorganic chemistry 2021-10, Vol.115, p.105179, Article 105179
• Main Authors: Zhang, Jian, Mu, Keman, Yang, Peng, Feng, Xinqian, Zhang, Di, Fan, Xiangyu, Wang, Qiantao, Mao, Shengjun
• Format: Article
• Language: English
• Subjects: Allylbenzene Derivatives - chemical synthesis; Allylbenzene Derivatives - chemistry; Allylbenzene Derivatives - therapeutic use; Animals; Anisoles - chemical synthesis; Anisoles - chemistry; Anisoles - therapeutic use; Anticonvulsants - chemical synthesis; Anticonvulsants - chemistry; Anticonvulsants - therapeutic use; Cells, Cultured; Disease Models, Animal; Epilepsy; Epilepsy - drug therapy; Male; Mice; Neuroprotective Agents - chemical synthesis; Neuroprotective Agents - chemistry; Neuroprotective Agents - therapeutic use; PTZ; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Structure-activity relationships; α-asarone
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.105179

[Display omitted] •In the present study, we compared the antiepileptic effects of α-asarone derivatives to explore their structure-activity relationships using the PTZ-induced seizure model.•Our research revealed that electron-donating methoxy groups in the 3,4,5-position on phenyl ring increased antiepileptic potency but the placement of other groups at different positions decreased activity.•Besides, in allyl moiety, the optimal activity was reached with either an allyl or a 1-butenyl group in conjugation with the benzene ring.•5 and 19 exerted better neuroprotective effects against epilepsy in vitro(cell) and in vivo(mouse) models. In the present study, we compared the antiepileptic effects of α-asarone derivatives to explore their structure-activity relationships using the PTZ-induced seizure model. Our research revealed that electron-donating methoxy groups in the 3,4,5-position on phenyl ring increased antiepileptic potency but the placement of other groups at different positions decreased activity. Besides, in allyl moiety, the optimal activity was reached with either an allyl or a 1-butenyl group in conjugation with the benzene ring. The compounds 5 and 19 exerted better neuroprotective effects against epilepsy in vitro (cell) and in vivo (mouse) models. This study provides valuable data for further exploration and application of these compounds as potential anti-seizure medicines.