Department of Chemistry, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany.
Department of Biophysics, Faculty of Science, Palacky University, 17. Listopadu 12, CZ-77146 Olomouc, Czech Republic.
J Inorg Biochem. 2018 Jul;184:69-78. doi: 10.1016/j.jinorgbio.2018.03.013. Epub 2018 Apr 5.
A series of four 2‑amino‑3‑cyano‑4‑(3/4‑pyridyl)‑4H‑benzo[h]chromenes 2a-d and their dichlorido(p‑cymene)ruthenium(II) complexes 3a-d were tested for antiproliferative, vascular-disruptive, anti-angiogenic and DNA-binding activity. The coordination of the 4‑pyridyl‑4H‑naphthopyrans 2 to ruthenium led to complexes with pleiotropic effects. Unlike the free ligands 2a-d, their ruthenium complexes 3a-d showed a significant affinity for DNA as demonstrated by electrophoretic mobility shift assays (EMSA) and ethidium bromide assays. Binding of 3a-d to calf thymus DNA proceeded about 10-times faster compared with cisplatin. Treatment of HT-29 colon carcinoma, 518A2 melanoma and MCF-7 breast cancer cells with 3a and 3b caused an accumulation of cells in the G2/M phase and an increase of the fraction of mitotic cells in the case of HT-29, due to alterations of the microtubule cytoskeleton as shown by immunofluorescence staining. Complexes 3b-c showed a dual effect on the vascular system. They suppressed angiogenesis in zebrafish embryos and they destroyed the vasculature of the chorioallantoic membrane (CAM) in fertilized chicken eggs. They also inhibited the vasculogenic mimicry, typical of U-87 glioblastoma cells in tube formation assays.
我们测试了一系列四个 2-氨基-3-氰基-4-(3/4-吡啶基)-4H-苯并[h]色烯 2a-d 和它们的二氯-(对-甲基环戊二烯)钌(II)配合物 3a-d 的抗增殖、血管破坏、抗血管生成和 DNA 结合活性。4-吡啶基-4H-萘并吡喃 2 与钌的配位导致具有多种效应的配合物。与游离配体 2a-d 不同，它们的钌配合物 3a-d 如电泳迁移率变动分析（EMSA）和溴化乙锭分析所示，对 DNA 表现出显著的亲和力。与顺铂相比，3a-d 与小牛胸腺 DNA 的结合速度快约 10 倍。用 3a 和 3b 处理 HT-29 结肠癌细胞、518A2 黑色素瘤细胞和 MCF-7 乳腺癌细胞导致细胞在 G2/M 期积累，并在 HT-29 中增加有丝分裂细胞的分数，这是由于微管细胞骨架的改变，如免疫荧光染色所示。配合物 3b-c 对血管系统有双重作用。它们在斑马鱼胚胎中抑制血管生成，在受精鸡胚的绒毛尿囊膜（CAM）中破坏血管系统。它们还抑制了 U-87 神经胶质瘤细胞在管形成测定中的血管生成拟态。
