SYNTHESIS AND DEVELOPMENT OF NEW ANTIBACTERIAL AGENTS INHIBITORS OF FTSZ

Elements of the bacterial cytoskeleton represent potential targets for antimicrobial compounds. FtsZ (Filamentous temperature sensitive Z) is a bacterial ancestor of eukaryotic tubulin. It possess markedly different structures than its eukaryotic analogue, making possible to develop specific inhibitors for the bacterial protein. The 3-methoxybenzamide (3-MBA) has a weak antibacterial activity against B. subtilis, it can easily penetrate bacterial cell and bind FtsZ at high ligand efficiency. The fluorinated 3-MBA analogue 2,6-difluoro-3-nonyloxybenzamide (compound 1) showed a significant activity against B. subtilis and S. aureus. Starting from the compound 1 we designed and synthesized a new series of derivatives that replaced the amide function with bioisosteric groups and new compounds differently substituted at the 3 position of the 2,6-difluoro-3-hydroxybenzamide.