Identification of 3-acetyl-2-aminoquinolin-4-one as a novel, nonpeptidic scaffold for specific calpain inhibitory activity.
A series of 3-acetyl-2-aminoquinolin-4-one derivatives selected from the Korean Chemical Bank were screened for calpain inhibitory activity by using a high-throughput fluorimetric calpain assay. We identified a potent and selective mu-calpain inhibitor, compound 17, whose specificity and efficacy for mu-calpain inhibition was better than MDL28170. Docking studies revealed that the efficacy of its inhibitory effect on calpain depended on the size and charge properties of the substitutions on the phenylamino ring.
College of Pharmacy & Division of Life & Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea.
Da-Hye
DH
Kang
Kyu-Yeon
KY
Jun
Jin Pyo
JP
Lee
Chwang Siek
CS
Pak
Younghwa
Y
Na
Youngjoo
Y
Kwon
D042462:4-Quinolones / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D000634:Aminoquinolines / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020134:Catalytic Domain; D015195:Drug Design; D005470:Fluorometry; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D013379:Substrate Specificity
D042462:4-Quinolones; D000634:Aminoquinolines; D010455:Peptides; D054852:Small Molecule Libraries; D002154:Calpain