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In vivo‐ and in silico‐driven identification of novel synthetic quinoxalines as anticonvulsants and AMPA inhibitors
Author(s) -
Abulkhair Hamada S.,
Elmeligie Salwa,
Ghiaty Adel,
ElMorsy Ahmed,
Bayoumi Ashraf H.,
Ahmed Hany E. A.,
ElAdl Khaled,
Zayed Mohamed F.,
Hassan Memy H.,
Akl Eman N.,
ElZoghbi Mona S.
Publication year - 2021
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.202000449
Subject(s) - pharmacophore , anticonvulsant , pentylenetetrazol , chemistry , pharmacology , ampa receptor , in vivo , in silico , perampanel , epilepsy , docking (animal) , stereochemistry , biochemistry , medicine , glutamate receptor , neuroscience , biology , adverse effect , receptor , nursing , gene , microbiology and biotechnology
The lack of effective therapies for epileptic patients and the potentially harmful consequences of untreated seizure incidents have made epileptic disorders in humans a major health concern. Therefore, new and more potent anticonvulsant drugs are continually sought after, to combat epilepsy. On the basis of the pharmacophoric structural specifications of effective α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) antagonists with an efficient anticonvulsant activity, the present work reports the design and synthesis of two novel sets of quinoxaline derivatives. The anticonvulsant activity of the synthesized compounds was evaluated in vivo according to the pentylenetetrazol‐induced seizure protocol, and the results were compared with those of perampanel as a reference drug. Among the synthesized compounds, 24 , 28 , 32 , and 33 showed promising activities with ED 50 values of 37.50, 23.02, 29.16, and 23.86 mg/kg, respectively. Docking studies of these compounds suggested that AMPA binding could be the mechanism of action of these derivatives. Overall, the pharmacophore‐based structural optimization, in vivo and in silico docking, and druglikeness studies indicated that the designed compounds could serve as promising candidates for the development of effective anticonvulsant agents with good pharmacokinetic profiles.