Diversity-Oriented Synthesis and Antibiofilm Evaluation of Furan-2-Carboxamides

A diversity-oriented collection of furan-2-carboxamides with antibiofilm activity against P. aeruginosa is reported. The design involved the bioisosteric replacement of the labile furanone ring by a furan-2-carboxamide moiety to explore its influence on biological activity. After evaluation, carbohydrazides and triazoles showed significant antibiofilm activity, and 4b resulted in the most remarkable compound (58 % inhibition). Furthermore, treating P. aeruginosa with three active carboxamides reduced some virulence factors (pyocyanin and proteases), confirming the anti-quorum sensing properties of the derivatives and suggesting LasR as a plausible target. Molecular docking proposed that carbohydrazides share a similar binding mode to related furanones inside LasR with an excellent docking score, while higher derivatives diminished in silico affinity.