RESUMO
We prepared a series of cinnamoyl-containing furanones by an affordable and short synthesis. The nineteen compounds hold a variety of substituents including electron-donating, electron-withdrawing, bulky and meta-substituted phenyls, as well as heterocyclic rings. Compounds showed antibiofilm activity in S. aureus, K. pneumoniae and, more pronounced, against P. aeruginosa. The disruption of quorum sensing (QS) was tested using the violacein test and molecular docking predicted the antagonism of LasR as a plausible mechanism of action. The trimethoxylated and diene derivatives showed the best antibiofilm and anti-QS properties, thus becoming candidates for further modifications.
Assuntos
Lactonas , Staphylococcus aureus , Antibacterianos/farmacologia , Proteínas de Bactérias/farmacologia , Biofilmes , Lactonas/farmacologia , Simulação de Acoplamento Molecular , Pseudomonas aeruginosa , Percepção de QuorumRESUMO
Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are some of the most prescribed medications for pain but the incidence of adverse effects -especially during chronic treatment- points out the requirement of new analgesics. In this study, we showed an efficient two-steps synthesis of diphenylamine-containing dipeptides consisting of a multicomponent process followed by a Buchwald-Hartwig cross-coupling reaction. We prepared 16 diphenylamine derivatives and evaluated their in vivo anti-inflammatory activity through an ear edema model using 12-O-tetradecanoylpholbol-13-acetate. Furthermore, the toxicity of the more potent compounds in the Artemia salina model and their cell viability using murine RAW 264.7 cells is reported. The fluorinated compound 10k becomes a reliable candidate since it reduced the TPA-induced edema to 92%, lacked cytotoxicity against murine macrophages, and had minimal toxicity in Artemia salina.