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From Dynamic Combinatorial Chemistry to in Vivo Evaluation of Reversible and Irreversible Myeloperoxidase Inhibitors.

ABSTRACT: The implementation of dynamic combinatorial libraries allowed the determination of highly active reversible and irreversible inhibitors of myeloperoxidase (MPO) at the nanomolar level. Docking experiments highlighted the interaction between the most active ligands and MPO, and further kinetic studies defined the mode of inhibition of these compounds. Finally, in vivo evaluation showed that one dose of irreversible inhibitors is able to suppress the activity of MPO after inducing inflammation.

SUBMITTER: Soubhye J

PROVIDER: S-EPMC5304337 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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From Dynamic Combinatorial Chemistry to <i>in Vivo</i> Evaluation of Reversible and Irreversible Myeloperoxidase Inhibitors.

Soubhye Jalal J Gelbcke Michel M Van Antwerpen Pierre P Dufrasne François F Boufadi Mokhtaria Yasmina MY Nève Jean J Furtmüller Paul G PG Obinger Christian C Zouaoui Boudjeltia Karim K Meyer Franck F

ACS medicinal chemistry letters 20161202 2

The implementation of dynamic combinatorial libraries allowed the determination of highly active reversible and irreversible inhibitors of myeloperoxidase (MPO) at the nanomolar level. Docking experiments highlighted the interaction between the most active ligands and MPO, and further kinetic studies defined the mode of inhibition of these compounds. Finally, <i>in vivo</i> evaluation showed that one dose of irreversible inhibitors is able to suppress the activity of MPO after inducing inflammat ...[more]

PMID: 28197313

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