TY - JOUR
T1 - Triazole-curcuminoids
T2 - A new class of derivatives for 'tuning' curcumin bioactivities?
AU - Caprioglio, Diego
AU - Torretta, Simone
AU - Ferrari, Maila
AU - Travelli, Cristina
AU - Grolla, Ambra A.
AU - Condorelli, Fabrizio
AU - Genazzani, Armando A.
AU - Minassi, Alberto
N1 - Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
PY - 2016/1/15
Y1 - 2016/1/15
N2 - Curcumin is a unique blend of pharmacophores responsible for the pleiotropy of this natural pigment. In the present study we have replaced the 1,3-dicarbonyl moiety with a 1,2,3-triazole ring to furnish a new class of triazole-curcuminoids as a possible strategy to generate new compounds with different potency and selectivity compared to curcumin. We obtained a proof-of-principle library of 28 compounds tested for their cytotoxicity (SY-SY5Y and HeLa cells) and for their ability to inhibit NF-κB. Furthermore, we also generated 1,3-dicarbonyl curcuminoids of selected click compounds. Triazole-curcuminoids lost their ability to be Michael's acceptors, yet maintained some of the features of the parent compounds and disclosed new ones. In particular, we found that some compounds were able to inhibit NF-κB without showing cytotoxicity, while others, unlike curcumin, activated NF-κB signalling. This validates the hypothesis that click libraries can be used to investigate the biological activities of curcumin as well as generate analogs with selected features.
AB - Curcumin is a unique blend of pharmacophores responsible for the pleiotropy of this natural pigment. In the present study we have replaced the 1,3-dicarbonyl moiety with a 1,2,3-triazole ring to furnish a new class of triazole-curcuminoids as a possible strategy to generate new compounds with different potency and selectivity compared to curcumin. We obtained a proof-of-principle library of 28 compounds tested for their cytotoxicity (SY-SY5Y and HeLa cells) and for their ability to inhibit NF-κB. Furthermore, we also generated 1,3-dicarbonyl curcuminoids of selected click compounds. Triazole-curcuminoids lost their ability to be Michael's acceptors, yet maintained some of the features of the parent compounds and disclosed new ones. In particular, we found that some compounds were able to inhibit NF-κB without showing cytotoxicity, while others, unlike curcumin, activated NF-κB signalling. This validates the hypothesis that click libraries can be used to investigate the biological activities of curcumin as well as generate analogs with selected features.
KW - 1,3-Dipolar cycloaddition
KW - Click chemistry
KW - Curcumin
KW - Curcuminoids
KW - NF-κB
UR - http://www.scopus.com/inward/record.url?scp=84952639694&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2015.11.044
DO - 10.1016/j.bmc.2015.11.044
M3 - Article
SN - 0968-0896
VL - 24
SP - 140
EP - 152
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 2
ER -