title: Targeting quorum sensing by designing azoline derivatives to inhibit the N-hexanoyl homoserine lactone-receptor CviR: Synthesis as well as biological and theoretical evaluations.
abstract: To counteract bacterial resistance, we investigated the interruption of quorum sensing mediated by non-classical bioisosteres of the N-hexanoyl homoserine lactone with an azoline core. For this purpose, a set of selected 2-substituted azolines was synthesized, establishing the basis for a new protocol to synthesize 2-amino imidazolines. The synthesized compounds were evaluated as inhibitors of violacein production in Chromobacterium violaceum. Theoretical studies on bioisostere-protein interactions were performed using CviR. The results show that some azolines decreased violacein production, suggesting an antiquorum sensing profile against Gram-negative bacteria. Docking and molecular dynamic simulations together with binding free energy calculations revealed the exact binding and inhibitory profiles. These theoretical results show relationship with the in vitro activity of the azoline series.
authors.affiliation: Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Química Orgánica, Campus Casco de Santo Tomás, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 México, D.F., Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Bucio-Cano
authors.affiliation: Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Química Orgánica, Campus Casco de Santo Tomás, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 México, D.F., Mexico. Electronic address: areyesarellano@yahoo.com.mx.
authors.forename: Alicia
authors.initials: A
authors.lastname: Reyes-Arellano
authors.affiliation: Instituto Politécnico Nacional, Escuela Superior de Medicina, Laboratorio de Modelado Molecular y Diseño de Fármacos, Campus Casco de Santo Tomás, 11340 México, D.F., Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Correa-Basurto
authors.affiliation: Instituto Politécnico Nacional, Escuela Superior de Medicina, Laboratorio de Modelado Molecular y Diseño de Fármacos, Campus Casco de Santo Tomás, 11340 México, D.F., Mexico.
authors.forename: Martiniano
authors.initials: M
authors.lastname: Bello
authors.affiliation: Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Química Orgánica, Campus Casco de Santo Tomás, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 México, D.F., Mexico.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Torres-Jaramillo
authors.affiliation: Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Química Orgánica, Campus Casco de Santo Tomás, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 México, D.F., Mexico.
authors.forename: Héctor
authors.initials: H
authors.lastname: Salgado-Zamora
authors.affiliation: Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Química Orgánica, Campus Casco de Santo Tomás, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 México, D.F., Mexico.
authors.forename: Everardo
authors.initials: E
authors.lastname: Curiel-Quesada
authors.affiliation: Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Química Orgánica, Campus Casco de Santo Tomás, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 México, D.F., Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Peralta-Cruz
authors.affiliation: Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Química Orgánica, Campus Casco de Santo Tomás, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 México, D.F., Mexico.
authors.forename: Alcives
authors.initials: A
authors.lastname: Avila-Sorrosa
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002861:Chromobacterium / Q000187:drug effects* / Q000502:physiology*; D002937:Cinoxacin / Q000737:chemistry / Q000494:pharmacology*; D056004:Molecular Dynamics Simulation; D053038:Quorum Sensing / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C088386:homoserine lactone; D002937:Cinoxacin; D015107:4-Butyrolactone
keywords: Azolines; Chromobacterium violaceum; Molecular dynamic simulation; Non classical bioisosteres; Quorum sensing