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

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.

Automated summary

Novel hydrazones based on (-)-carvone were synthesized and characterized using various spectroscopic and spectrometric techniques. The compounds demonstrated anticonvulsant activity in electroshock and chemical-induced convulsions models, and their significant analgesic effect may be attributed to binding to TRPA1/TRPV1 ion channels.