jm4011725_si_001.pdf (2.7 MB)
Optimization of O3‑Acyl Kojic Acid Derivatives as Potent and Selective Human Neutrophil Elastase Inhibitors
journal contributionposted 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. Guedes
Human 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.