Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition.
Details
Serval ID
serval:BIB_B5AF259B23AE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition.
Journal
Journal of Medicinal Chemistry
ISSN
1520-4804 (Electronic)
ISSN-L
0022-2623
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
55
Number
11
Pages
5270-5290
Language
english
Notes
Publication types: Journal Article
Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. Starting from the scaffold of our previously discovered IDO1 inhibitor 4-phenyl-1,2,3-triazole, we used computational structure-based methods to design more potent ligands. This approach yielded highly efficient low molecular weight inhibitors, the most active being of nanomolar potency both in an enzymatic and in a cellular assay, while showing no cellular toxicity and a high selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO). A quantitative structure-activity relationship based on the electrostatic ligand-protein interactions in the docked binding modes and on the quantum chemically derived charges of the triazole ring demonstrated a good explanatory power for the observed activities.
Pubmed
Web of science
Create date
22/07/2012 21:08
Last modification date
20/08/2019 15:24