Resveratrol-Schiff Base Hybrid Compounds with Selective Antibacterial Activity: Synthesis, Biological Activity, and Computational Study.

Nowadays, antimicrobial resistance is a serious concern associated with the reduced efficacy of traditional antibiotics and an increased health burden worldwide. In response to this challenge, the scientific community is developing a new generation of antibacterial molecules. Contributing to this effort, and inspired by the resveratrol structure, five new resveratrol-dimers ( 9a - 9 e ) and one resveratrol-monomer ( 10a ) were synthetized using 2,5-dibromo-1,4-diaminobenzene ( 8 ) as the core compound for Schiff base bridge conformation. These compounds were evaluated in vitro against pathogenic clinical isolates of Pseudomonas aeruginosa , Staphylococcus aureus , Bacillus sp., and Listeria monocytogenes . Antibacterial activity measurements of resveratrol-Schiff base derivatives ( 9a - 9e ) and their precursors ( 4 - 8 ) showed high selectivity against Listeria monocytogenes , being 2.5 and 13.7 times more potent than chloramphenicol, while resveratrol showed an EC 50 > 320 µg/mL on the same model. Moreover, a prospective mechanism of action for these compounds against L . monocytogenes strains was proposed using molecular docking analysis, finding a plausible inhibition of internalin C (InlC), a surface protein relevant in bacteria-host interaction. These results would allow for the future development of new molecules for listeriosis treatment based on compound 8 .