Isolation, synthesis and structure-activity relationships of gallotannin derivatives as cathepsin C inhibitor.

Summary

The authors isolated and synthesized gallotannin derivatives from Rhois Galla and identified 1,2,3,6-tetra-O-galloyl-β-D-glucose as a cathepsin C inhibitor, providing structure–activity relationship insights. Given CatC’s central role in neutrophil protease activation, these scaffolds suggest a potential therapeutic route for neutrophilic lung injury, ARDS, and COVID-19.

Key Findings

• Gallotannin derivatives were isolated from Rhois Galla, and 1,2,3,6-tetra-O-galloyl-β-D-glucose showed cathepsin C inhibitory activity.
• Structure–activity relationship analysis was conducted to relate galloylation patterns to CatC inhibition.
• Targets a key upstream enzyme in neutrophil protease activation, relevant to acute lung injury, ARDS, and COVID-19.

Clinical Implications

While preclinical, CatC inhibition could attenuate neutrophil-driven tissue damage in acute lung injury and ARDS; these scaffolds warrant optimization and in vivo testing.

Limitations

• Abstract indicates in vitro inhibition without reported in vivo efficacy or pharmacokinetics
• Potency metrics (e.g., IC50) are truncated in the abstract; full quantitative data are not available here

Future Directions

Optimize potency/selectivity, assess pharmacokinetics/toxicity, and evaluate efficacy in animal models of neutrophilic lung injury and ARDS.