title: Imidazolines as non-classical bioisosteres of N-acyl homoserine lactones and quorum sensing inhibitors.
abstract: A series of selected 2-substituted imidazolines were synthesized in moderate to excellent yields by a modification of protocols reported in the literature. They were evaluated as potential non-classical bioisosteres of AHL with the aim of counteracting bacterial pathogenicity. Imidazolines 18a, 18e and 18f at various concentrations reduced the violacein production by Chromobacterium violaceum, suggesting an anti-quorum sensing profile against Gram-negative bacteria. Imidazoline 18b did not affect the production of violacein, but had a bacteriostatic effect at 100 μM and a bactericidal effect at 1 mM. Imidazoline 18a bearing a hexyl phenoxy moiety was the most active compound of the series, rendering a 72% inhibitory effect of quorum sensing at 100 μM. Imidazoline 18f bearing a phenyl nonamide substituent presented an inhibitory effect on quorum sensing at a very low concentration (1 nM), with a reduction percentage of 28%. This compound showed an irregular performance, decreasing inhibition at concentrations higher than 10 μM, until reaching 100 μM, at which concentration it increased the inhibitory effect with a 49% reduction percentage. When evaluated on Serratia marcescens, compound 18f inhibited the production of prodigiosin by 40% at 100 μM.
authors.affiliation: Department of Organic Chemistry, National Polytechnic Institute, National School of Biological Sciences, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 México, D.F., Mexico.
authors.forename: Alicia
authors.initials: A
authors.lastname: Reyes-Arellano
authors.affiliation: Department of Organic Chemistry, National Polytechnic Institute, National School of Biological Sciences, 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: Department of Organic Chemistry, National Polytechnic Institute, National School of Biological Sciences, Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 México, D.F., Mexico.
authors.forename: Mabel
authors.initials: M
authors.lastname: Montenegro-Sustaita
authors.affiliation: Department of Biochemistry, National Polytechnic Institute, National School of Biological Sciences, 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: Department of Organic Chemistry, National Polytechnic Institute, National School of Biological Sciences, 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
mesh_terms: D054742:Acyl-Butyrolactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002861:Chromobacterium / Q000378:metabolism*; D007211:Indoles / Q000378:metabolism; D011353:Prodigiosin / Q000096:biosynthesis; D053038:Quorum Sensing / Q000187:drug effects*; D012706:Serratia marcescens / Q000378:metabolism*
chemical_list: D054742:Acyl-Butyrolactones; D007211:Indoles; D011353:Prodigiosin; C063155:violacein