Synthesis, cytotoxicity of new 4-arylidene curcumin analogues and their multi-functions in inhibition of both NF-κB and Akt signalling.
A series of new 4-arylidene curcumin analogues (4-arylidene-1,7-bisarylhepta-1,6-diene-3,5-diones) were synthesized and found to be potent antiproliferative agents against a panel of cancer cell lines at submicromolar to low micromolar concentrations by SRB assay. Their inhibitory abilities against NF-κB was evaluated by High Content Analysis (HCA) based immunofluorescence assay; and the Akt signalling inhibition was determined by fluorescence polarization assay and western blot respectively. The Structure-Activity Relationship was discussed. Our results revealed that 4-arylidene curcumin analogues may work in a multi-targets manner in cancer cell.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510275, PR China.
Yinglin
Y
Zuo
Jianing
J
Huang
Binhua
B
Zhou
Shuni
S
Wang
Weiyan
W
Shao
Cuige
C
Zhu
Li
L
Lin
Gesi
G
Wen
Hongyang
H
Wang
Jun
J
Du
Xianzhang
X
Bu
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003474:Curcumin / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D062105:Molecular Docking Simulation; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D003474:Curcumin