Synthesis, anticonvulsant activity, and molecular modeling studies of novel 1-phenyl/1-(4-chlorophenyl)-2-(1H-triazol-1-yl)ethanol ester derivatives

DOĞAN İ. S., ÖZDEMİR Z., SARI S., Bozbey I., KARAKURT A., Sarac S.

MEDICINAL CHEMISTRY RESEARCH, cilt.27, sa.9, ss.2171-2186, 2018 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27 Sayı: 9
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1007/s00044-018-2225-6
  • Dergi Adı: MEDICINAL CHEMISTRY RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.2171-2186
  • Anahtar Kelimeler: Anticonvulsant activity, (Arylalkyl)azoles, Ester, Molecular docking, Synthesis, Triazole, BENZODIAZEPINE-BINDING-SITE, AMINOBUTYRIC ACID(A) RECEPTORS, OXIME ETHER DERIVATIVES, GABA(A) RECEPTORS, ANTIMICROBIAL ACTIVITIES, DRUG DEVELOPMENT, STRUCTURAL REQUIREMENTS, BIOLOGICAL EVALUATION, ACCURATE DOCKING, ALPHA(1) SUBUNIT
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

A series of new ester derivatives were synthesized by the reaction of various acids with 1-phenyl/1-(4-chlorophenyl)-2-(1H-triazol-1-yl)ethanol and in vivo screened for their anticonvulsant activity. The title compounds were screened against MES and ScM seizure tests according to a modified version of the Epilepsy Therapy Screening Program (ETSP) protocol of the National Institutes of Health (NIH). Their neurotoxic effects were evaluated by the rotarod test. All the compounds showed protection against MES and/or ScM-induced seizures at 30 mg/kg without neurotoxicity. More compounds were found active in the ScM test and at lower dose than the MES test. Physicochemical and pharmacokinetic profiles of the compounds were predicted by QikProp. Using molecular docking approach we tried to get insights into their possible anticonvulsant mechanisms.