title: Synthesis of cinnamoyl ketoamides as hybrid structures of antioxidants and calpain inhibitors.
abstract: The excessive calpain activation causes serious cellular damage or even cell death in neurological disorders such as stroke and Alzheimer's disease. Oxidative stress has also been implicated in the initiation or progression of neurodegenerative diseases. In the present studies, a series of cinnamoyl ketoamides 4a-4j were synthesized as hybrid structures of antioxidants and calpain inhibitors. Cinnamoyl ketoamides, possessing an alkyl chain at the α-position, showed potent μ-calpain inhibitory activities indicating that the cinnamoyl skeleton can be regarded as an acyclic variant of calpain inhibitory chromone carboxamide 2. Among synthesized, compound 4e was the most potent inhibitor of μ-calpain (IC(50)=0.13 μM) and also exhibited strong antioxidant activities in DPPH and superoxide anion radical scavenging and lipid peroxidation inhibition assay systems.
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Yeong Jae
authors.initials: YJ
authors.lastname: Yoo
authors.forename: Dong Hyuk
authors.initials: DH
authors.lastname: Nam
authors.forename: Seo Yun
authors.initials: SY
authors.lastname: Jung
authors.forename: Jae Wan
authors.initials: JW
authors.lastname: Jang
authors.forename: Hyoung Ja
authors.initials: HJ
authors.lastname: Kim
authors.forename: Changbae
authors.initials: C
authors.lastname: Jin
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004789:Enzyme Activation / Q000187:drug effects*; D006023:Glycoproteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D000577:Amides; D000975:Antioxidants; D002934:Cinnamates; D006023:Glycoproteins; D007659:Ketones; C039304:calpain inhibitors