Linked Life Data

21277783

Source:http://linkedlifedata.com/resource/pubmed/id/21277783

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-2-14
pubmed:abstractText
Cathepsin V is a lysosomal cysteine peptidase highly expressed in thymus, testis and corneal epithelium. Eleven acridone alkaloids were isolated from Swinglea glutinosa (Bl.) Merr. (Rutaceae), with eight of them being identified as potent and reversible inhibitors of cathepsin V (IC(50) values ranging from 1.2 to 3.9 ?M). Detailed mechanistic characterization of the effects of these compounds on the cathepsin V-catalyzed reaction showed clear competitive inhibition with respect to substrate, with dissociation constants (K(i)) in the low micromolar range (2, K(i)=1.2 ?M; 6, K(i)=1.0 ?M; 7, K(i)=0.2 ?M; and 11, K(i)=1.7 ?M). Molecular modeling studies provided important insight into the structural basis for binding affinity and enzyme inhibition. Experimental and computational approaches, including biological evaluation, mode of action assessment and modeling studies were successfully employed in the discovery of a small series of acridone alkaloid derivatives as competitive inhibitors of catV. The most potent inhibitor (7) has a K(i) value of 200 nM.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1464-3391
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1477-81
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Acridone alkaloids as potent inhibitors of cathepsin V.
pubmed:affiliation
Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't