Chemical Biology and Drug Design
Chemical Biology and Drug Design
5 years ago

Physicochemical and biological evaluation of a cinnamamide derivative R,S-(2E)-1-(3-hydroxypiperidin-1-yl)-3-phenylprop-2-en-1-one (KM-608) for nervous system disorders

Physicochemical and biological evaluation of a cinnamamide derivative R,S-(2E)-1-(3-hydroxypiperidin-1-yl)-3-phenylprop-2-en-1-one (KM-608) for nervous system disorders
Agnieszka Gunia-Krzyżak, Wojciech Nitek, Anna M. Waszkielewicz, Ewa Żesławska, Henryk Marona, Florence M. Bareyre
A cinnamamide scaffold has been successfully incorporated in several compounds possessing desirable pharmacological activities in central and peripheral nervous system such as anticonvulsant, antidepressant, neuroprotective, analgesic, anti-inflammatory, muscle relaxant, and sedative/hypnotic properties. R,S-(2E)-1-(3-hydroxypiperidin-1-yl)-3-phenylprop-2-en-1-one (KM-608), a cinnamamide derivative, was synthesized, its chemical structure was confirmed by means of spectroscopy and crystallography, and additionally, thermal analysis showed that it exists in one crystalline form. The compound was evaluated in vivo in rodents as anticonvulsant, antiepileptogenic, analgesic, and neuroprotective agent. The beneficial properties of the compound were found in animal models of seizures evoked electrically (maximal electroshock test, 6-Hz) and chemically (subcutaneous pentylenetetrazole seizure test) as well as in three animal models of epileptogenesis: corneal-kindled mice, hippocampal-kindled rats, and lamotrigine-resistant amygdala-kindled rats. Quantitative pharmacological parameters calculated for the tested compound were comparable to those of currently used antiepileptic drugs. In vivo pharmacological profile of KM-608 corresponds with the activity of valproic acid. R,S-(2E)-1-(3-hydroxypiperidin-1-yl)-3-phenylprop-2-en-1-one (KM-608), a cinnamamide derivative, with confirmed structure and purity was tested in mice and rats. The compound is a potent anticonvulsant and antiepileptogenic agent. In vivo pharmacological profile of KM-608 corresponds with the activity of valproic acid.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/cbdd.12943

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