TY - JOUR
T1 - Targeting quorum sensing by designing azoline derivatives to inhibit the N-hexanoyl homoserine lactone-receptor CviR
T2 - Synthesis as well as biological and theoretical evaluations
AU - Bucio-Cano, Alejandro
AU - Reyes-Arellano, Alicia
AU - Correa-Basurto, José
AU - Bello, Martiniano
AU - Torres-Jaramillo, Jenifer
AU - Salgado-Zamora, Héctor
AU - Curiel-Quesada, Everardo
AU - Peralta-Cruz, Javier
AU - Avila-Sorrosa, Alcives
N1 - Publisher Copyright:
© 2015 The Authors. Published by Elsevier Ltd.
PY - 2015/12/15
Y1 - 2015/12/15
N2 - 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.
AB - 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.
KW - Azolines
KW - Chromobacterium violaceum
KW - Molecular dynamic simulation
KW - Non classical bioisosteres
KW - Quorum sensing
UR - http://www.scopus.com/inward/record.url?scp=84949500139&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2015.10.046
DO - 10.1016/j.bmc.2015.10.046
M3 - Artículo
C2 - 26654469
SN - 0968-0896
VL - 23
SP - 7565
EP - 7577
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 24
ER -