Work

Imide-based enones: A new scaffold that inhibits biofilm formation in Gram-negative pathogens

Year: 2025

Type: article

Abstract: We prepared a series of enones containing different substituents as potential antibiofilm molecules. The design considered the structural features previously found in N- acylhomoserine lactones, but it replaced the labile furanone with different imides portions. After evaluation, some of the analogs inhibited 50 % or more the formation of the biofilm from P. aeruginosa or A. baumannii ; moreover, substituents attached at the phenyl ring, the size of the enone as well as the type of imide seemed relevant for the selectivity against the tested pathogens . In the end, we performed a molecular docking study using the crystallized LasR to describe the main interactions of the ligand-receptor complex and propose a plausible mechanism of action. • 25 imide-based enones were prepared from a three-step sequence. • Some imides reduced biofilm of P. aeruginosa or A. baumannii 50 % or more. • None of the bioactive enones reduced bacterial growth. • In the case of P. aeruginosa , molecular docked confirmed LasR as a potential target. • The series becomes an attractive scaffold for the design of more potent antibiofilm agents.

Source: Bioorganic & Medicinal Chemistry Letters

DOI: 10.1016/j.bmcl.2025.130206

Authors: J. Israel Barrera-Hernández, Jesús R. Pérez-Velázquez, Ángel Ramírez-Trinidad, Jesús Oria-Hernández, Eduardo Hernández-Vázquez

Institutions: Universidad Nacional Autónoma de México, Secretaria de Salud, Instituto Nacional de Pediatria

Language: English

Topic: Bacterial biofilms and quorum sensing

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,880