Paper publication "Design and synthesis of benzofuran- and naphthalene-fused thiazinones as antimycobacterial agents"
| by Helena Costa Pereira
We are delighted to share that our TTA colleague, François Keiff, has published his first major contribution in the field of antimycobacterial nitro-benzothiazinones, in Archiv der Pharmazie.
It all started as a small side-project, where François investigated, with help of Thibault, structure expansion possibilities of the nitro-benzothiazinone (BTZ) scaffold via scaffold-hopping. Synthetic challenge consisted into respecting the substitution pattern of parent drug BTZ-043 to ensure similar binding mode to DprE1. Molecular docking simulations performed by another TTA colleague, Freddy Bernal confirms this hypothesis. DFT calculation at last showed that substitution pattern impacts the redox potential of the nitro moiety to the reactive nitroso intermediate, first step in the covalent inhibition of DprE1 by nitro-BTZ. They believe that this new approach will be applicable to further substitution modifications of the benzylic counterpart of nitro BTZ.
We hope this is the first of many papers to come, congrats, François!