Synthesis, antibacterial and cytotoxic evaluation of cytosporone E and analogs

The history of antibacterial discovery has revealed that natural products, especially secondary metabolites, represent privileged chemical matters for the antibacterial discovery. Among these metabolites, several natural phthalides exhibit interesting antibacterial activities, such as cytosporone E isolated from endophyte ascomycetes Diaporthe and Cytospora sp. We describe herein the synthesis and the pharmacomulations on the positions 3, 4 and 6 of cytosporone E, then the in vitro antibacterial evaluation of these compounds against Staphylococcus aureus including resistant strains, Escherichia coli and Pseudomonas aeruginosa. The evaluation of the cytotoxicity of the most active compounds against human bronchial epithelial cells was performed in order to check their safety.