Discovery of Novel Antibacterial Agents Active Against Methicillin-ResistantStaphylococcus aureus from Combinatorial Benzopyran Libraries

In vitro antibacterial potencies similar to that of vancomycin against several strains of methicillin-susceptible and -resistant Staphylococcus aureus were found for some novel benzopyran-derived antibacterial agents (see picture; R=H, tBu; X=O, S). Lead compounds were identified from compound libraries, generated by split-and-pool combinatorial synthesis, by using high-throughput antibacterial screening. A preliminary optimization was achieved by molecular fine-tuning through design and chemical synthesis followed by further biological testing.