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Updated: Jan 12, 2026
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
Investigations of gold(I) complexes as inhibitors of caspase-1
Srirajkumar Ranganathan1, Isabella D Reda1, Helen A Gustafson1
1Department of Chemistry and Biochemistry, College of Science and Health, DePaul University, Chicago, IL 60614, USA.
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.
Insights
Gold(I) complexes effectively inhibit caspase-1, a key enzyme in inflammation. This discovery highlights their potential as anti-inflammatory drugs targeting cysteine-dependent proteins in diseases like gout and arthritis.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Immunology
Background:
- Caspase-1 is a critical enzyme in the inflammasome, initiating inflammatory responses.
- Inflammation mediated by caspase-1 is linked to diseases such as gout and rheumatoid arthritis.
- Gold complexes are known for their anti-inflammatory potential.
Purpose of the Study:
- To investigate the inhibitory effects of gold(I) complexes on caspase-1 activity.
- To explore the potential of gold complexes as therapeutic agents for inflammatory diseases.
Main Methods:
- Screening of various gold(I) molecular species for caspase-1 inhibition.
- Determination of inhibition constants (KI) for effective compounds.
Main Results:
- Several gold(I) complexes demonstrated significant inhibition of caspase-1.
- The most potent inhibitors, PMe3AuCl and PPh3AuCl, exhibited KI values of 8 nM and 9 nM, respectively.
- Inhibition occurred in the nanomolar range, indicating high efficacy.
Conclusions:
- Gold(I) complexes are effective inhibitors of caspase-1.
- The aurophilicity of sulfur in caspase-1's active site likely contributes to this inhibition.
- Gold(I) complexes represent a promising class of drugs for targeting cysteine-dependent enzymes in inflammatory conditions.
