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See detailStructure-based design of benzoxazoles as new inhibitors for D-alanyl-D-alanine ligase
Tytgat, Isabelle; Vandevuer, Stéphane; Ortmans, Isabelle et al

in QSAR & Combinatorial Science (2009), 28(11-12), 1394-1404

d-Alanyl – d-alanine ligase is an enzyme which catalyzes the dimerization of d-alanine, and, as such, has an essential role in bacterial cell wall biosynthesis. It has been shown that inhibition of d ... [more ▼]

d-Alanyl – d-alanine ligase is an enzyme which catalyzes the dimerization of d-alanine, and, as such, has an essential role in bacterial cell wall biosynthesis. It has been shown that inhibition of d-alanyl – d-alanine ligase prevents bacterial growth. d-Alanyl – d-alanine ligase represents therefore a viable antimicrobial target. The 3D structure of this enzyme complexed with a phosphinophosphate inhibitor has been reported, which allows for structure-based design studies. Four softwares (LUDI, MCSS, Autodock, and Glide) developed either for fragment or full-molecule docking were compared and scored for their ability to position in the active site four prototypic ligands: two inhibitors, i.e. a phosphinophosphate derivative and d-cycloserine, d-alanine and d-alanyl – d-alanine. Best performances were obtained with Glide and MCSS. A short series of novel derivatives based on a 2-phenylbenzoxazole scaffold was designed de novo on the basis of computational data. The best compound was found to fully inhibit the d-alanyl – d-alanine ligase of E. faecalis with an IC50 of 400 mM. [less ▲]

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See detailThree-dimensional quantitative structure-activity relationship of MT3 melatonin binding site ligands: a comparative molecular field analysis
Farce, Amaury; Dilly, Sébastien ULg; Sabaouni, Ahmed et al

in QSAR & Combinatorial Science (2007), 26(7), 820-827

The Three-Dimensional Quantitative Structure –Activity Relationship (3D-QSAR) approach using Comparative Molecular Field Analysis (CoMFA) was applied to a series of 39 compounds evaluated as MT3 binding ... [more ▼]

The Three-Dimensional Quantitative Structure –Activity Relationship (3D-QSAR) approach using Comparative Molecular Field Analysis (CoMFA) was applied to a series of 39 compounds evaluated as MT3 binding site ligands. The X-ray crystal structure of MT3/quinone reductase 2 was used to obtain the putative bioactive conformation of these ligands. Five statistically significant models were obtained from the randomly constituted training sets (30 compounds) and subsequently validated with the corresponding test sets (nine compounds). The best predictive model (n=30, q2=0.608, N=3, r2=0.897, s=0.288, F=75.4) can predict inhibitory activity for a wide range of compounds and offers important structural insight into designing MT3 ligands prior to their synthesis. [less ▲]

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