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Synthesis, anticonvulsant screening, and molecular modeling studies of new arylalkylimidazole oxime ether derivatives
Author(s) -
Özdemir Zeynep,
Sari Suat,
Karakurt Arzu,
Dalkara Sevim
Publication year - 2019
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21491
Subject(s) - anticonvulsant , chemistry , oxime , pharmacology , in vivo , pharmacokinetics , epilepsy , stereochemistry , medicinal chemistry , medicine , microbiology and biotechnology , psychiatry , biology
Abstract In this study, 15 new oxime ether derivatives were synthesized and their anticonvulsant activities were screened in vivo. The compounds were synthesized by the reaction of various alkyl halides with 1‐(2‐naphthyl)‐2‐(1 H ‐imidazol‐1‐yl)ethanone oxime. Their anticonvulsant activities were determined using acute (maximal electroshock, subcutaneous metrazol [SCM], and 6 Hz seizure test) and chronic (corneal‐kindled mouse) seizure models, their neurotoxic effects were evaluated by models of behavioral toxicity according to the Epilepsy Therapy Screening Program protocol of the NIH. All our compounds were protective in at least one of the tests. Quantification studies were applied to some of the active compounds and the intraperitoneal ED 50 values in mice were found between 25.48 and 99.56 mg/kg. Some pharmacokinetic properties of the compounds were predicted in silico and molecular docking studies were performed to provide insights into their possible anticonvulsant mechanism regarding their SCM activity.