Novel (-)-carvone derivatives as potential anticonvulsant and analgesic agents

Creative Commons License

Nesterkina M., Barbalat D., Konovalova I., Shishkina S., ATAKAY M., SALİH B., ...Daha Fazla

NATURAL PRODUCT RESEARCH, cilt.35, sa.23, ss.4978-4987, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 35 Sayı: 23
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1080/14786419.2020.1756804
  • Dergi Adı: NATURAL PRODUCT RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Aquatic Science & Fisheries Abstracts (ASFA), Biotechnology Research Abstracts, CAB Abstracts, CINAHL, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.4978-4987
  • Anahtar Kelimeler: carvone, hydrazones, phenoxyacetic acid, X-ray diffraction, TRP channels, analgesic affect, anticonvulsant activity
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Novel hydrazones based on (-)-carvone were synthesized via condensation of terpenoid with 4-R-phenoxyacetic acid hydrazides. The structure of target compounds was established by FT-IR, Raman, H-1-NMR and C-13-NMR spectral analysis, FAB/ESI mass spectrometry. (-)-Carvone hydrazones were proven to exist as Z/E geometrical isomers about C = N bond using ion mobility-tandem mass spectrometry (IM-MS/MS). Single crystal X-ray diffraction study was applied to determine molecular and crystal structure of compound 3e. Hydrazones 3a-3e were evaluated as potential anticonvulsant agents after their oral administration against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in mice. Analgesic activity of compounds was investigated by topical application on models of capsaicin and AITC-induced pain. The present findings indicate that (-)-carvone derivatives afforded seizure protection both at short (1 h) and long (24 h) time period by blocking electroshock- and chemical-induced convulsions. Hydrazones binding to TRPA1/TRPV1 ion channels was proposed as possible mechanism explaining significant analgesic effect of compounds.