139565-46-1Relevant articles and documents
Novel anthraquinone inhibitors of human leukocyte elastase and cathepsin G
Zembower,Kam,Powers,Zalkow
, p. 1597 - 1605 (2007/10/02)
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 μM, and also inhibit CatG with IC50 values ranging from 25 to 55 μM. 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 K(i) values in the range of 10-7 M. All of the inhibitors described are completely reversible, with no evidence of acyl-enzyme formation detected.
