Design, synthesis and biological evaluation of ( E )-3-(3,4,5-trimethoxyphenyl) acrylic acid (TMCA) amide derivatives as anticonvulsant and sedative agents

AbstractIn this article, a novel series of (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (TMCA) amide derivatives1-18 were designed and synthesized by a facile and one-pot step, which were achieved with good yields using 1-hydroxybenzotriazole (HOBT) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) as activation system. All the synthesized derivatives were biologically evaluated for their anticonvulsant, sedative activity and neurotoxicity using the maximal electroshock (MES) model,sc-pentylenetetrazol (PTZ) model, pentobarbital sodium-induced sleeping model, and locomotor activity tests, respectively. Among them, compounds4, 9 and16 exhibited good anticonvulsant activity in primary evaluation. Furthermore, compound4 is the most effective anticonvulsant and sedative agent in subsequent tests, while the low threshold of toxicity of compound4 is vigilant. Compounds9 and16 also performed significantly anticonvulsant activity in subsequent tests with weak toxicity. The molecular modeling experiments also predicted good binding interactions of the obtained active molecules with the GABA transferas. Therefore, it could be concluded that the synthesized derivatives4, 9 and16 would represent useful lead compounds for further investigation in the development of anticonvulsant and sedative agents.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research