Novel inhibitors of FtsZ as antimicrobial agents: synthesis and Structure Activity Relationship

The number and prevalence of drug-resistant bacterial strains are in constant growth1 and even the most recently approved antimicrobials act on a restricted number of “traditional” targets, thus increasing the probability for the development of resistance. This poses a number of challenges which remain largely unmet and there is a strong need for the discovery of potent and versatile drugs with innovative mechanisms of action. FtsZ (Filamentous temperature sensitive Z) emerged as a promising target, due to its ubiquitous expression in bacteria and to its essential role in cell division. In recent years, a variety of molecules proved able to interact with this protein and to selectively inhibit bacterial cell division. Our research group developed interesting derivatives displaying good antibacterial activities against Staphylococcus aureus (methicillin-resistant and sensible strains), vancomycin-resistant Enterococcus faecalis and Mycobacterium tuberculosis. The aim of the present communication is to summarize the Structure-Activity Relationship for differently substituted heterocycles, linked by a methylenoxy-bridge to the 2,6-difluorobenzamide.