Reference : Synthesis, biological activity, and X-ray crystal structural analysis of diaryl ether...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Synthesis, biological activity, and X-ray crystal structural analysis of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 1: 4'-substituted triclosan derivatives.
Freundlich, Joel S. [> >]
Anderson, John W. [> >]
Sarantakis, Dimitri [> >]
Shieh, Hong-Ming [> >]
Yu, Min [> >]
Valderramos, Juan-Carlos [> >]
Lucumi Moreno, Edinson mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Kuo, Mack [> >]
Jacobs, William R. Jr [> >]
Fidock, David A. [> >]
Schiehser, Guy A. [> >]
Jacobus, David P. [> >]
Sacchettini, James C. [> >]
Bioorganic & Medicinal Chemistry Letters
[en] Animals ; Antimalarials/chemical synthesis/chemistry/pharmacology ; Crystallography, X-Ray ; Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)/antagonists & inhibitors ; Molecular Structure ; Plasmodium falciparum/drug effects/enzymology ; Triclosan/analogs & derivatives/chemistry
[en] A structure-based approach has been taken to develop 4'-substituted analogs of triclosan that target the key malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Many of these compounds exhibit nanomolar potency against purified PfENR enzyme and modest (2-10microM) potency against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite. X-ray crystal structures of nitro 29, aniline 30, methylamide 37, and urea 46 demonstrate the presence of hydrogen-bonding interactions with residues in the active site and point to future rounds of optimization to improve compound potency against purified enzyme and intracellular parasites.
Researchers ; Professionals ; Students

File(s) associated to this reference

Fulltext file(s):

Limited access
Freundlich et al_2005_Synthesis, biological activity, and X-ray crystal structural analysis of diaryl.pdfPublisher postprint267.78 kBRequest a copy

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.