Synthesis, anticonvulsant screening, and molecular modeling studies of new arylalkylimidazole oxime ether derivatives

ÖZDEMİR Z., SARI S., KARAKURT A., DALKARA S.

DRUG DEVELOPMENT RESEARCH, cilt.80, sa.2, ss.269-280, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 80 Sayı: 2
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1002/ddr.21491
  • Dergi Adı: DRUG DEVELOPMENT RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.269-280
  • Anahtar Kelimeler: anticonvulsant, (Arylalkyl)azole, imidazole, nafimidone, oxime ether, BENZODIAZEPINE-BINDING-SITE, AMINOBUTYRIC ACID(A) RECEPTORS, GABA(A) RECEPTORS, ANTIMICROBIAL ACTIVITIES, STRUCTURAL REQUIREMENTS, ACCURATE DOCKING, DRUG SOLUBILITY, ALPHA-SUBUNIT, GAMMA-SUBUNIT, PREDICTION
  • İnönü Üniversitesi Adresli: Evet

Özet

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-(1H-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 ED50 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.