Linked Life Data

19158658

Source:http://linkedlifedata.com/resource/pubmed/id/19158658

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-1-22
pubmed:abstractText
The Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is an important cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites. The discovery of new FP-2 inhibitors is now a hot topic in the search for potential malaria treatments. In this study, a series of novel small molecule FP-2 inhibitors have been designed and synthesized based on three regional optimizations of the lead (R)-2-phenoxycarboxamido-3-(1H-indol-3-yl)-N-benzylpropanamide(1), which was identified using structure-based virtual screening in conjunction with surface plasmon resonance (SPR)-based binding assays. Four compounds--1, 2b, 2k and 2l--showed moderate FP-2 inhibition activity, with IC(50) values of 10.0-39.4 microM, and the inhibitory activity of compound 2k was approximately 3-fold better than that of the prototype compound 1 and may prove useful for the development of micromolar level FP-2 inhibitors. Preliminary SAR data was obtained, while molecular modeling revealed that introduction of H-bond donor or/and acceptor atoms to the phenyl ring moiety in the C region would be likely to produce some additional H-bond interactions, which should consequently enhance molecular bioactivity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1420-3049
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
494-508
pubmed:dateRevised
2009-10-27
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
2-amido-3-(1H-indol-3-yl)-N-substituted-propanamides as a new class of falcipain-2 inhibitors. 1. Design, synthesis, biological evaluation and binding model studies.
pubmed:affiliation
School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, PR China. jinzh@mail.ecust.edu.cn
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't