Design of β-Keto Esters with Antibacterial Activity: Synthesis, In Vitro Evaluation, and Theoretical Assessment of Their Reactivity and Quorum-Sensing Inhibition Capacity

This work proposes the design of β-keto esters as antibacterial compounds. The was based on structure autoinducer bacterial quorum sensing, N-(3-oxo-hexanoyl)-l-homoserine lactone (3-oxo-C6-HSL). Eight ester analogues were synthesised with good yields and spectroscopically characterised, showing that compounds only present in their tautomer form. We carried out a computational analysis reactivity ADME (absorption, distribution, metabolism, excretion) properties well molecular docking dynamics calculations LasR LuxS quorum-sensing (QS) proteins, which are involved resistance to antibiotics. results show all exhibit reliable compound 7 can electrophile toxicity. theoretical study shows 6 8 differential local regarding rest series. Compound presents most promising potential terms its ability interact QS proteins efficiently according calculations. An initial vitro antimicrobial screening performed against human pathogenic bacteria Pseudomonas aeruginosa Staphylococcus aureus phytopathogenic syringae Agrobacterium tumefaciens. Compounds panel studied.