Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
|
pubmed:dateCreated |
1992-6-9
|
pubmed:abstractText |
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.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anthraquinones,
http://linkedlifedata.com/resource/pubmed/chemical/CTSG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin G,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins,
http://linkedlifedata.com/resource/pubmed/chemical/Leukocyte Elastase,
http://linkedlifedata.com/resource/pubmed/chemical/Pancreatic Elastase,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases
|
pubmed:status |
MEDLINE
|
pubmed:month |
May
|
pubmed:issn |
0022-2623
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
1
|
pubmed:volume |
35
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1597-605
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:1578486-Anthraquinones,
pubmed-meshheading:1578486-Cathepsin G,
pubmed-meshheading:1578486-Cathepsins,
pubmed-meshheading:1578486-Humans,
pubmed-meshheading:1578486-Leukocyte Elastase,
pubmed-meshheading:1578486-Pancreatic Elastase,
pubmed-meshheading:1578486-Serine Endopeptidases,
pubmed-meshheading:1578486-Structure-Activity Relationship
|
pubmed:year |
1992
|
pubmed:articleTitle |
Novel anthraquinone inhibitors of human leukocyte elastase and cathepsin G.
|
pubmed:affiliation |
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta 30332.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|