Chromene-dihydropyrimidinone and xanthene-dihydropyrimidinone hybrids: design, synthesis, and antibacterial and antibiofilm activities

A series of eleven chromene-dihydropyrimidinone and eleven xanthene-dihydropyrimidinone hybrid compounds were easily synthesized through a sequential multicomponent reaction followed by copper-catalyzed alkyne-azide cycloaddition reaction. The antibiofilm and antibacterial activities of hybrids were evaluated against Staphylococcus aureus and Pseudomonas aeruginosa and the antibiofilm property was dose dependent. Most of the compounds showed antibiofilm activity against S. aureus without inhibiting its growth. In vivo, worms acutely or chronically exposed to the 15a hybrid presented decreased survival rate, brood size, and body length and increased number of apoptotic corpses; however these effects were only observed at the highest concentrations tested. In silico analyses suggested a novel target for this molecule in the SOS pathway for inducible DNA damage repair. Thus, the hybrids are promising compounds against bacterial biofilms which are associated with difficult-to-treat chronic infections.