title: Cinnamamide Derivatives for Central and Peripheral Nervous System Disorders--A Review of Structure-Activity Relationships.
abstract: The cinnamamide scaffold has been incorporated in to the structure of numerous organic compounds with therapeutic potential. The scaffold enables multiple interactions, such as hydrophobic, dipolar, and hydrogen bonding, with important molecular targets. Additionally, the scaffold has multiple substitution options providing the opportunity to optimize and modify the pharmacological activity of the derivatives. In particular, cinnamamide derivatives have exhibited therapeutic potential in animal models of both central and peripheral nervous system disorders. Some have undergone clinical trials and were introduced on to the pharmaceutical market. The diverse activities observed in the nervous system included anticonvulsant, antidepressant, neuroprotective, analgesic, anti-inflammatory, muscle relaxant, and sedative properties. Over the last decade, research has focused on the molecular mechanisms of action of these derivatives, and the data reported in the literature include targeting the γ-aminobutyric acid type A (GABAA ) receptors, N-methyl-D-aspartate (NMDA) receptors, transient receptor potential (TRP) cation channels, voltage-gated potassium channels, histone deacetylases (HDACs), prostanoid receptors, opioid receptors, and histamine H3 receptors. Here, the literature data from reports evaluating cinnamic acid amide derivatives for activity in target-based or phenotypic assays, both in vivo and in vitro, relevant to disorders of the central and peripheral nervous systems are analyzed and structure-activity relationships discussed.
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow (Poland). agnieszka.gunia@uj.edu.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gunia-Krzyżak
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow (Poland).
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Pańczyk
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow (Poland).
authors.forename: Anna M
authors.initials: AM
authors.lastname: Waszkielewicz
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow (Poland).
authors.forename: Henryk
authors.initials: H
authors.lastname: Marona
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000737:chemistry* / Q000627:therapeutic use; D002934:Cinnamates / Q000737:chemistry* / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D011954:Receptors, Dopamine / Q000737:chemistry / Q000378:metabolism; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents; D002934:Cinnamates; D056572:Histone Deacetylase Inhibitors; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C411088:cinnamamide
keywords: anti-inflammatory agents; anticonvulsants; antidepressants; cinnamamides; medicinal chemistry; neuroprotective agents; structure-activity relationships