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Issue 5, 2012
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Potent inhibition of Ca2+-dependent activation of calpain-1 by novel mercaptoacrylates

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Abstract

Calpain-1 is a Ca2+-activated cytosolic cysteine protease. Its activation has been linked to extravasation into inflamed tissue of white blood cells, especially neutrophils. Calpain-1 may therefore be an anti-inflammatory target for therapeutic intervention. 24 novel monohalogenated phenyl and indole mercaptoacrylic acid derivatives were synthesised. The location and nature of the ring-coupled halides strongly influenced the potency of these compounds to inhibit calpain activation. Several of the calpain-1 inhibitors showed IC50 values in the low nanomolar range and prevented cell shape change of neutrophils, a necessary prelude to their migration from the blood in the body.

Graphical abstract: Potent inhibition of Ca2+-dependent activation of calpain-1 by novel mercaptoacrylates

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Publication details

The article was received on 09 Nov 2011, accepted on 25 Nov 2011 and first published on 30 Nov 2011


Article type: Concise Article
DOI: 10.1039/C2MD00280A
Citation: Med. Chem. Commun., 2012,3, 566-570
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    Potent inhibition of Ca2+-dependent activation of calpain-1 by novel mercaptoacrylates

    S. E. Adams, C. Parr, D. J. Miller, R. K. Allemann and M. B. Hallett, Med. Chem. Commun., 2012, 3, 566
    DOI: 10.1039/C2MD00280A

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