title: 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.
abstract: 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.
authors.affiliation: Chair of Organic Chemistry, Department of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Agnieszka
authors.identifier: 0000-0003-4162-4760
authors.initials: A
authors.lastname: Gunia-Krzyżak
authors.affiliation: Department of Chemistry, Institute of Biology, Pedagogical University, Kraków, Poland.
authors.forename: Ewa
authors.identifier: 0000-0003-1946-9370
authors.initials: E
authors.lastname: Żesławska
authors.affiliation: Institute of Clinical Neuroimmunology, Hospital and Biomedical Center (BMC), Ludwig-Maximilians University, Munich, Germany.|Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Florence M
authors.initials: FM
authors.lastname: Bareyre
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Kraków, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Nitek
authors.affiliation: Chair of Organic Chemistry, Department of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Waszkielewicz
authors.affiliation: Chair of Organic Chemistry, Department of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Marona
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy*; D002934:Cinnamates / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D018360:Crystallography, X-Ray; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000700:Analgesics; D000927:Anticonvulsants; D002934:Cinnamates; C411088:cinnamamide
keywords: anticonvulsant; antiepileptogenic; cinnamamide; traumatic brain injury