Synthesis of N, N-Bis([1,1′-Biphenyl]-4-ylmethyl)-4-morpholinoaniline derivatives via SMC reaction: Assessing their anti-seizure potential through electroencephalogram evaluation and molecular docking studies

Abstract

A new series of N, N-bis([1,1′-biphenyl]-4-ylmethyl)-4-morpholinoaniline derivatives (6a − h, 7i) were synthesized and evaluated their anticonvulsant potential through in vivo and in silico studies. 6 Hz Psychomotor and acute pentylenetetrazol (PTZ) seizure models were used for in vivo anticonvulsant activity. A glide program in a standard precision (SP) model, and the targeted protein 8G5G, 3O7P, and 1PW4 were used for in silico studies. Through in silico and in vivo experiments, it was determined that compounds 6f and 6 h, which exhibit no neurotoxicity when compared to standard drugs (levetiracetam and diazepam), were the most potent among all the synthesized compounds (6a-h, 7i). Multiple binding affinities of synthetic compounds (6a-h, 7i) to localize binding receptors were also observed by in silico study. Based on the docking studies of active molecules with different targets, the aforementioned drugs most likely work via binding to the SV2A transporter and GABA-A receptor.

Keywords

• N, N-bis(4-bromobenzyl)-4-morpholinyl amine
• Suzuki Miyaura reactions
• Anticonvulsant potential
• Acute PTZ and 6 Hz psychomotor seizure model
• Electroencephalogram
• Molecular docking studies