1ZXL: Synthesis, Biological Activity, And X-Ray Crystal Structural Analysis Of Diaryl Ether Inhibitors Of Malarial Enoyl Acp Reductase. Part 1:4'-Substituted Triclosan Derivatives

Citation:
Abstract
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.
PDB ID: 1ZXLDownload
MMDB ID: 39534
PDB Deposition Date: 2005/6/8
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 1ZXL: tetrameric; determined by author and by software (PISA,PQS)
Molecular Components in 1ZXL
Label Count Molecule
Proteins (4 molecules)
4
Enoyl-acyl Carrier Reductase
Molecule annotation
Chemicals (8 molecules)
1
4
2
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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