Schmitt Florian, Gold Madeleine, Begemann Gerrit, Andronache Ion, Biersack Bernhard, Schobert Rainer
Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, 95447 Bayreuth, Germany.
Developmental Biology, University of Bayreuth, Universitaetsstrasse 30, 95447 Bayreuth, Germany.
Bioorg Med Chem. 2017 Sep 1;25(17):4894-4903. doi: 10.1016/j.bmc.2017.07.039. Epub 2017 Jul 21.
A series of 14 analogs of the curcuminoid EF24, (3E,5E)-3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone, bearing fluorine or pentafluorothio substituents, were prepared and tested for antiproliferative, vascular-disruptive, and antiangiogenic activity, as well as for their influence on other cancer-relevant targets. They proved antiproliferative against eight cancer cell lines with IC values in the low single-digit micromolar to triple-digit nanomolar range. Like EF24, the hexafluoro 3c and 3d and bis(pentafluorothio) 4f derivatives arrested HT-29 colon carcinoma cells in G2/M phase of the cell cycle, yet inhibited angiogenesis, e.g. in zebrafish larvae, to a much greater extent. The antimigratory effects in 518A2 melanoma cells of 3c, its regioisomer 3d, and of 4f, originate from an inhibition of NF-κB translocation. Moreover, 3c and 3d showed potential as vascular-disruptive agents in chorioallantoic/vitelline membrane (CA/VM) assays.
制备了一系列14种姜黄素类似物EF24（(3E,5E)-3,5-双[(2-氟苯基)亚甲基]-4-哌啶酮）的类似物，其带有氟或五氟硫取代基，并对其抗增殖、血管破坏和抗血管生成活性以及它们对其他癌症相关靶点的影响进行了测试。它们对8种癌细胞系具有抗增殖作用，IC值在低个位数微摩尔到三位数纳摩尔范围内。与EF24一样，六氟衍生物3c和3d以及双(五氟硫)衍生物4f使HT-29结肠癌细胞停滞在细胞周期的G2/M期，但在更大程度上抑制血管生成，例如在斑马鱼幼虫中。3c及其区域异构体3d以及4f对518A2黑色素瘤细胞的抗迁移作用源于对NF-κB易位的抑制。此外，3c和3d在绒毛尿囊/卵黄膜（CA/VM）试验中显示出作为血管破坏剂的潜力。
