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|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
Guedes, Rita C.
Santos, Maria M. M.
|Keywords: ||Vinyl sulfone|
|Issue Date: ||2010|
|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 Reviewed: ||yes|
|Publisher version: ||http://www.sciencedirect.com/science/article/pii/S022352341000379X|
|Appears in Collections:||FF-DQFT - Artigos em Revistas Internacionais|
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