Publication date: Feb 09, 2025
Cathepsin C (CatC), a key enzyme in neutrophil serine protease activation, is a promising target for treating neutrophilic inflammatory diseases like acute lung injury, ARDS, and COVID-19. Despite its therapeutic potential, no CatC inhibitors are currently available. In this study, a series of gallotannin derivatives were isolated from the traditional Chinese medicine Rhois Galla. Among these, 1,2,3,6-tetra-O-galloyl-β-d-glucose (1) inhibited CatC with an IC of 32. 69 +/- 2. 95 nM. Subsequently, fifteen derivatives of 1 were synthesized and evaluated, revealing key structure-activity relationships. Compound 1 emerged as a potent and selective CatC inhibitor, while a novel synthetic derivative, 15, demonstrated dual inhibitory effects on CatC and cathepsin L. Structural features, including O-galloyl groups at positions 1, 2, and 6 of β-glucose and a hydrogen donor at position 4, were identified as favorable for CatC inhibition. These findings provide valuable insights for developing novel CatC inhibitors.
| Concepts | Keywords |
|---|---|
| Cathepsin | Cathepsin C |
| Chinese | Cathepsin L |
| Glucose | Gallotannin |
| Valuable | Neutrophil serine proteases |
| Structure–activity relationships |
Semantics
| Type | Source | Name |
|---|---|---|
| drug | DRUGBANK | Tannic acid |
| disease | MESH | lung injury |
| disease | MESH | COVID-19 |
| drug | DRUGBANK | D-glucose |
| drug | DRUGBANK | Dextrose unspecified form |