Linked Life Data

16033259

Source:http://linkedlifedata.com/resource/pubmed/id/16033259

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2005-7-21
pubmed:abstractText
In an approach to discover new inhibitors of trypanothione reductase from Trypanosoma cruzi, the causative agent of Chagas' disease, a virtual high-throughput screening was performed. Two structurally new types of inhibitors emerged, the antimicrobial chlorhexidine {1,1'-hexamethylenebis[5-(4-chlorophenyl)biguanide]}, a linear competitive inhibitor (K(i) = 2 +/- 1 microM), and a piperidine derivative acting as mixed inhibitor (K(i) = 6.2 +/- 2 microM and K(i)' = 8.5 +/- 2 microM). Neither compound interferes with human glutathione reductase. Based on chlorhexidine, different series of compounds were synthesized and studied as inhibitors of T. cruzi trypanothione reductase. Most efficient derivatives were three bis(amidines) showing mixed type inhibition with K(i,slope) and K(i,int) values of 2-5 microM and 16-47 microM, respectively. Although these compounds did not exert an improved inhibitory potency compared to chlorhexidine, the change from competitive to mixed-type inhibition is advantageous, since substrate accumulation does not overcome inhibition. Remarkably, all three derivatives carried two copies of an identical 2-methoxy-4-methyl-1-(phenylmethoxy)benzene substituent.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4793-802
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Inhibitors of Trypanosoma cruzi trypanothione reductase revealed by virtual screening and parallel synthesis.
pubmed:affiliation
Biochemie-Zentrum, Universität Heidelberg, Im Neuenheimer Feld 504, D-69120 Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't