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Eur J Med Chem. 2015 Jun 15;98:49-53. doi: 10.1016/j.ejmech.2015.05.019. Epub 2015 May 16.

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

Author information

1
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK.
2
Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK.
3
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK. Electronic address: C.W.G.Fishwick@leeds.ac.uk.

Abstract

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.

KEYWORDS:

Bis-amido epoxides molecular modelling; FXIII-A; Thrombosis

PMID:
26005023
DOI:
10.1016/j.ejmech.2015.05.019
[Indexed for MEDLINE]
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