Synthesis and Identification of New 4-Arylidene Curcumin Analogues as Potential Anticancer Agents Targeting Nuclear Factor-κB Signaling Pathway
ABSTRACT A series of curcumin analogues including new 4-arylidene curcumin analogues (4-arylidene-1,7-bisarylhepta-1,6-diene-3,5-diones) were synthesized. Cell growth inhibition assays revealed that most 4-arylidene curcumin analogues can effectively decrease the growth of a panel of lung cancer cells at submicromolar and low micromolar concentrations. High content analysis technology coupled with biochemical studies showed that this new class of 4-arylidene curcumin analogues exhibits significantly improved NF-κB inhibition activity over the parent compound curcumin, at least in part by inhibiting IκB phosphorylation and degradation via IKK blockage; selected 4-arylidene curcumin analogues also reduced the tumorigenic potential of cancer cells in a clonogenic assay.
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ABSTRACT: Here, we report studies on the antioxidant activity and redox behavior of curcumin and its structurally modified synthetic analogues. We have synthesized a number of analogues of curcumin which abrogate its keto-enol tautomerism or substitute the methylene group at the centre of its heptadione moiety implicated in the hydride transfer and studied their redox property. From cyclic voltammetric studies, it is demonstrated that H- atom transfer from CH2 group at the center of the heptadione link also plays an important role in the antioxidant properties of curcumin along with that of its phenolic–OH group. In addition, we also show that the conversion of 1, 3- dicarbonyl moiety of curcumin to an isosteric heterocycle as in pyrazole curcumin, which decreases its rotational freedom, leads to an improvement of its redox properties as well as its antioxidant activityElectrochimica Acta 01/2015; 151:574. · 4.09 Impact Factor
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ABSTRACT: Several recent developments suggest that the human glyoxalase I (GLO I) is a potential target for anti-tumor drug development. In present study, a series of curcumin derivatives with high inhibitory activity against human GLO I were discovered. Inhibition constant (K(i)) values of compounds 8, 9, 10, 11 and 13 to GLO I are 4.600μM, 2.600μM, 3.200μM, 3.600μM and 3.600μM, respectively. To elucidate the structural features of potent inhibitors, docking-based three-dimensional structure-activity relationship (3D-QSAR) analyses were performed. Satisfactory agreement between experiment and theory suggests that comparative molecular similarity index analysis (CoMSIA) modeling exhibit much better correlation and predictive power. The cross-validated q(2) value is 0.638 while no-validation r(2) value is 0.930. Integrated with docking-based 3D-QSAR CoMSIA modeling, molecular surface property (electrostatic and steric) mapping and molecular dynamics simulation, a set of receptor-ligand binding models and bio-affinity predictive models for rational design of more potent inhibitors of GLO I are established.Bioorganic & medicinal chemistry 02/2011; 19(3):1189-96. DOI:10.1016/j.bmc.2010.12.039 · 2.95 Impact Factor
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ABSTRACT: In the title compound, C(21)H(20)O(4), the central hepta-trienone unit is approximately planar, with a maximum atomic deviation of 0.1121 (11) Å; the two benzene rings are twisted with respect to the hepta-trienone mean plane by 2.73 (5) and 29.31 (4)°. The mol-ecule exists in the enol form and the hy-droxy group forms an intra-molecular hydrogen bond with the neighboring carbonyl group. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure.Acta Crystallographica Section E Structure Reports Online 08/2011; 67(Pt 8):o1885. DOI:10.1107/S160053681102469X · 0.35 Impact Factor