Design, synthesis, molecular modeling and biological evaluation of novel 2,3-dihydrophthalazine-1,4-dione derivatives as potential anticonvulsant agents

作者：El Helby Abdel Ghany A; Ayyad Rezk R; Sakr Helmy M; Abdelrahim Adel S; El Adl K; Sherbiny Farag S; Eissa Ibrahim H^*; Khalifa Mohamed M^*

来源：Journal of Molecular Structure, 2017, 1130: 333-351.

DOI：10.1016/j.molstruc.2016.10.052

• 2,3-Dihydrophthalazine-1,4-dione
• Molecular modeling
• Anticonvulsant
• GABA-A

In view of their expected anticonvulsant activity, some novel derivatives of 2,3-dihydrophthalazine-1,4-dione 4-22 were designed, synthesized and evaluated using pentylenetetrazole (PTZ) and picrotoxin as convulsion-inducing models. Moreover, the most active compounds were tested against electrical induced convulsion using maximal electroshock (MES) models of seizures. Most of the tested compounds showed considerable anticonvulsant activity in at least one of the anticonvulsant tests. Compounds 13 and 14g were proved to be the most potent compounds of this series with relatively low toxicity in the median lethal dose test when compared with the reference drug. Molecular modeling studies were done to verify the biological activity. The obtained results showed that the most potent compounds could be useful as a template for future design, optimization, and investigation to produce more active analogues.

• 出版日期2017-2-15