Please use this identifier to cite or link to this item: http://hdl.handle.net/10451/3844
Title: Synthesis and evaluation of vinyl sulfones as caspase-3 inhibitors. A structure-activity study
Authors: Newton, Ana S.
Glória, Paulo M. C.
Gonçalves, Lídia M.
Santos, Daniel J. V. A. dos
Moreira, Rui
Guedes, Rita C.
Santos, Maria M. M.
Keywords: Vinyl sulfone
Caspase-3 inhibitor
Michael acceptor
Irreversible inhibitor
Issue Date: 2010
Publisher: Elsevier
Citation: Newton, Ana S. ; Glória, Paulo M. C. ; Gonçalves, Lídia M.; Santos, Daniel J. V. A. dos ; Moreira, Rui; Guedes, Rita C. ; Santos, Maria M. M.Synthesis and evaluation of vinyl sulfones as caspase-3 inhibitors. A structure-activity study, European Journal of Medicinal Chemistry , 45, 3858-3863, 2010.
Abstract: The first structure–activity relationship study of vinyl sulfones as caspase-3 inhibitors is reported. A series of 12 vinyl sulfones was synthesized and evaluated for two downstream caspases (caspases-3 and -7). Dipeptidyl derivatives were significantly superior to their counterparts containing only Asp at P1, as caspase-3 inhibitors. Fmoc-Val-Asp-trans-CH CH–SO2Me was the most potent inhibitor of caspase-3 in the series, with a IC50 of 29 μM and a second-order rate constant of inactivation, kinact/Ki, of 1.5 M−1 s−1. Computational studies suggest that the second amino acid occupies position S3 of the enzyme. In addition, Fmoc-Val-Asp-trans-CH CH–SO2Ph was inactive for caspase-7 for the tested concentrations.
Peer review: yes
URI: http://dx.doi.org/10.1016/j.ejmech.2010.05.039
http://hdl.handle.net/10451/3844
ISSN: 0223-5234
Publisher Version: http://www.sciencedirect.com/science/article/pii/S022352341000379X
Appears in Collections:FF-DQFT - Artigos em Revistas Internacionais

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