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. 2025 Oct 29:275:113133.
doi: 10.1016/j.jinorgbio.2025.113133. Online ahead of print.

Investigations of gold(I) complexes as inhibitors of caspase-1

Srirajkumar Ranganathan  1 , Isabella D Reda  1 , Helen A Gustafson  1 , Callista G Polasek  1 , Ehxciquiel Jaeroume M Camacho  1 , Roger D Sommer  2 , Kyle A Grice  1 , Caitlin E Karver  3
Affiliations

Investigations of gold(I) complexes as inhibitors of caspase-1

Srirajkumar Ranganathan et al. J Inorg Biochem. .

Abstract

Caspase-1 is a key enzyme in the inflammasome that turns on the inflammation cascade. It has been implicated in a variety of disease conditions, including gout, rheumatoid arthritis and inflammatory diseases. Gold complexes have long been studied for their anti-inflammatory properties. The active site of caspase-1 contains a cysteine thiolate, and given that sulfur is aurophilic, we hypothesized that gold complexes would inhibit caspase-1. In this work, we examined a series of gold(I) molecular species for inhibition of caspase-1. It was found that many of the complexes were effective inhibitors at the nanomolar range, with the most effective being PMe3AuCl (KI = 8 nM) and PPh3AuCl (KI = 9 nM). This highlights the value of gold(I) complexes as drug molecules that target cysteine-dependent proteins for disease states.

Keywords: Caspase-1; Cysteine-dependent enzymes; Gold; Metal-based drugs.

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Conflict of interest statement

Declaration of competing interest None.

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