(±) cis-Bisamido epoxides: A novel series of potent FXIII-A inhibitors.

Autor: Avery CA; School of Chemistry, University of Leeds, Leeds LS2 9JT, UK., Pease RJ; Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK., Smith K; Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK., Boothby M; Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK., Buckley HM; Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK., Grant PJ; Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK., Fishwick CW; School of Chemistry, University of Leeds, Leeds LS2 9JT, UK. Electronic address: C.W.G.Fishwick@leeds.ac.uk.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2015 Jun 15; Vol. 98, pp. 49-53. Date of Electronic Publication: 2015 May 16.
DOI: 10.1016/j.ejmech.2015.05.019
Abstrakt: A novel class of potent FXIII-A inhibitors containing a (±) cis-bisamido epoxide pharmacophore is described. The compounds display highly potent inhibition of FXIII-A (IC50 = 5-500 nM) in an in vitro assay. In contrast to other types of previously described covalent transglutaminase inhibitors, the bis-amido epoxides exhibited no measurable reactivity with glutathione, therefore possibly rendering this class of compounds suitable for future in vivo investigations. Additionally, the compounds show selective inhibition for FXIII-A against the cysteine protease, cathepsin S although they proved to have similar potency with a closely related transglutaminase, TGII, to that observed for FXIII-A.
(Copyright © 2015 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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