title: Synthesis and biological evaluation of chromone carboxamides as calpain inhibitors.
abstract: Excessive calpain activations contribute to serious cellular damage and have been found in many pathological conditions. Novel chromone carboxamides derived from ketoamides were prepared and evaluated for mu-calpain inhibition. Among synthesized, compound 2i was the most potent calpain inhibitor with an IC(50) value of 0.24 +/- 0.11 microM comparable to the activity of peptide aldehyde calpain inhibitor MDL 28,170. Furthermore, compound 2i showed higher selectivity for mu-calpain over two related cysteine proteases cathepsin B and cathepsin L, suggesting the chromone ring as a good scaffold for selective mu-calpain inhibitors.
authors.affiliation: Life Sciences Division, Korea Institute of Science & Technology, Cheongryang, Seoul.
authors.forename: Kwang Seob
authors.initials: KS
authors.lastname: Lee
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Seo
authors.forename: Yong Ha
authors.initials: YH
authors.lastname: Lee
authors.forename: Ha Dong
authors.initials: HD
authors.lastname: Kim
authors.forename: Moon Ho
authors.initials: MH
authors.lastname: Son
authors.forename: Bong Young
authors.initials: BY
authors.lastname: Chung
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
authors.forename: Changbae
authors.initials: C
authors.lastname: Jin
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D002154:Calpain / Q000037:antagonists & inhibitors*; D002867:Chromones / Q000138:chemical synthesis* / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D002867:Chromones; D015853:Cysteine Proteinase Inhibitors; D002154:Calpain