Novel anthraquinone inhibitors of human leukocyte elastase and cathepsin G

J Med Chem. 1992 May 1;35(9):1597-605. doi: 10.1021/jm00087a014.


A large series of variously substituted anthraquinones has been synthesized and assayed for inhibitory capacity against human leukocyte elastase (HLE) and cathepsin G (CatG), two serine proteinases implicated in diseases characterized by the abnormal degradation of connective tissue, such as pulmonary emphysema and rheumatoid arthritis. It was found that 2-alkyl-1,8-dihydroxyanthraquinone analogues are competitive inhibitors of HLE with IC50 values ranging from 4 to 10 microM, and also inhibit CatG with IC50 values ranging from 25 to 55 microM. Consequently, analogues containing the 2-alkyl-1-hydroxy-8-methoxyanthraquinone substitution pattern inhibit HLE to the same magnitude as for the compounds above, but show very little inhibition of CatG. Anthraquinones containing long, hydrophobic n-butyl carbonate moieties in the 1- and 8-positions in conjunction with a third hydrophobic substituent in the 2- or 3-position are highly selective for HLE, with Ki values in the range of 10(-7) M. All of the inhibitors described are completely reversible, with no evidence of acyl-enzyme formation detected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthraquinones / chemical synthesis
  • Anthraquinones / pharmacology*
  • Cathepsin G
  • Cathepsins / antagonists & inhibitors*
  • Humans
  • Leukocyte Elastase
  • Pancreatic Elastase / antagonists & inhibitors*
  • Serine Endopeptidases
  • Structure-Activity Relationship


  • Anthraquinones
  • Cathepsins
  • Serine Endopeptidases
  • CTSG protein, human
  • Cathepsin G
  • Pancreatic Elastase
  • Leukocyte Elastase