Synthesis and biological evaluation of chromone carboxamides as calpain inhibitors.
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.
Lee
Kwang Seob
KS
Life Sciences Division, Korea Institute of Science & Technology, Cheongryang, Seoul.
Seo
Seon Hee
SH
Lee
Yong Ha
YH
Kim
Ha Dong
HD
Son
Moon Ho
MH
Chung
Bong Young
BY
Lee
Jae Yeol
JY
Jin
Changbae
C
Lee
Yong Sup
YS
D002154:Calpain / Q000037:antagonists & inhibitors*; D002867:Chromones / Q000138:chemical synthesis* / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*
D002867:Chromones; D015853:Cysteine Proteinase Inhibitors; D002154:Calpain