Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-amino-4-quinolone Derivatives as Biofilm Inhibitors

Molecules

OsvaldoJavier Quintana-Romero¹  Armando Ariza-Castolo¹  MarianaPaola Espinosa-Valdés²  Sara Borbolla-Alvarez²  DiegoFernando García-Del Río²  AnaElena Delgado-Espinosa²  MarcoA. Loza-Mejía²  Anabelle Cerón-Nava²  JuanFrancisco Sánchez-Tejeda² 

[1] Departamento de Química Orgánica, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Av. Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico;Facultad de Ciencias Químicas, Universidad La Salle-México. Av. Benjamin Franklin 45, Cuauhtémoc, Mexico City 06140, Mexico;

关键词: quorum sensing;    biofilm;    quinolones;    molecular docking;    molecular dynamics;   

DOI  :  10.3390/molecules24020327

来源: DOAJ

【 摘 要 】

Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complement for current and new antibacterial therapies. Based on the structure of 2-alkyl-3-hydroxy-4-quinolone and N-acylhomoserine lactone, molecules that act as mediators of quorum sensing and biofilm formation in Pseudomonas aeruginosa, we designed, prepared, and evaluated the biofilm inhibition properties of long chain amide derivatives of 2-amino-4-quinolone in Staphylococcus aureus and P. aeruginosa. All compounds had higher biofilm inhibition activity in P. aeruginosa than in S. aureus. Particularly, compounds with an alkyl chain of 12 carbons exhibited the highest inhibition of biofilm formation. Docking scores and molecular dynamics simulations of the complexes of the tested compounds within the active sites of proteins related to quorum sensing had good correlation with the experimental results, suggesting the diminution of biofilm formation induced by these compounds could be related to the inhibition of these proteins.

【 授权许可】

Unknown