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


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

NATURAL PRODUCT RESEARCH, vol.35, no.23, pp.4978-4987, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 23
  • Publication Date: 2021
  • Doi Number: 10.1080/14786419.2020.1756804
  • Journal Name: NATURAL PRODUCT RESEARCH
  • Journal Indexes: 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
  • Page Numbers: pp.4978-4987
  • Keywords: carvone, hydrazones, phenoxyacetic acid, X-ray diffraction, TRP channels, analgesic affect, anticonvulsant activity
  • Hacettepe University Affiliated: Yes

Abstract

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.