TY - JOUR
T1 - Imidazolines as Non-classical bioisosteres of N-Acyl homoserine lactones and quorum sensing inhibitors
AU - Reyes-Arellano, Alicia
AU - Bucio-Cano, Alejandro
AU - Montenegro-Sustaita, Mabel
AU - Curiel-Quesada, Everardo
AU - Salgado-Zamora, Héctor
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - AHL bioisosteres
KW - Chromobacterium violaceum
KW - Imidazoline synthesis
KW - Quorum sensing
UR - http://www.scopus.com/inward/record.url?scp=84857670062&partnerID=8YFLogxK
U2 - 10.3390/ijms13021284
DO - 10.3390/ijms13021284
M3 - Artículo
C2 - 22408391
SN - 1661-6596
VL - 13
SP - 1284
EP - 1299
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 2
ER -