jm4011725_si_001.pdf (2.7 MB)
Optimization of O3‑Acyl Kojic Acid Derivatives as Potent and Selective Human Neutrophil Elastase Inhibitors
journal contribution
posted on 2013-12-12, 00:00 authored by Susana D. Lucas, Lídia M. Gonçalves, Luís A.
R. Carvalho, Henrique F. Correia, Eduardo M. R. Da Costa, Romina A. Guedes, Rui Moreira, Rita C. GuedesHuman
neutrophil elastase (HNE) is an attractive target for treating chronic
and acute inflammatory lung diseases. An optimization campaign of
the kojic acid scaffold to develop new potent HNE inhibitors is reported. O3-Pivaloyl derivatives were shown to be the
most potent inhibitors with IC5o values down to 80 nM.
These compounds presented excellent selectivity and cytotoxicity profiles
with suitable ligand efficiency.
