Author/Authors :
Anne-Marie Periers، نويسنده , , Patrick Laurin، نويسنده , , Didier Ferroud، نويسنده , , Jean-Luc Haesslein، نويسنده , , Michel Klich، نويسنده , , Claudine Dupuis-Hamelin، نويسنده , , Pascale Mauvais، نويسنده , , Patrice Lassaigne، نويسنده , , Alain Bonnefoy، نويسنده , , Branislav Musicki، نويسنده ,
Abstract :
The synthesis and biological profile in vitro of a series of coumarin inhibitors of gyrase B bearing a N-propargyloxycarbamate at C-3′ of noviose is presented. Replacement of the 5-methylpyrrole-2-carboxylate of coumarin drugs with an N-propargyloxycarbamate bioisostere leads to analogues with improved antibacterial activity. Analysis of crystal structures of coumarin antibiotics with the 24 kDa N-terminal domain of the gyrase B protein provides a rational for the excellent inhibitory potency of C-3′ N-alkoxycarbamates.
