An in vivo active 1,2,5-oxadiazole Pt(II) complex: A promising anticancer agent endowed with STAT3 inhibitory properties
An in vivo active 1,2,5-oxadiazole Pt(II) complex: A promising anticancer agent endowed with STAT3 inhibitory properties
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DOI：
10.1016/j.ejmech.2017.03.017
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发表时间：
2017-05-05
影响因子：
6.7
通讯作者：
Rimoldi, Isabella
中科院分区：
文献类型：
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作者：
Porta, Federica;Facchetti, Giorgio;Rimoldi, Isabella
合成了带有1，2，5-恶二唑配体（1-3）的新的Pt（II）络合物（Pt-1- 3），表征并评价了它们破坏STAT 3二聚化的能力。配体3中心点HCl显示出对HCT-116细胞的细胞毒性作用（IC 50 = 95.2 μ M）和与STAT 3（IC 50 = 8.2 μ M）相对于STATI（IC 50> 30 μ M）相互作用的选择性能力。其相应的铂络合物Pt-3表现出增加的细胞毒性（IC 50 = 18.4 μ M）和与STAT 3的更强的相互作用（IC 50 = 1.4 μ M），导致其信号传导途径的抑制。还在基于细胞的测定中评价Pt-3对p53表达和STAT 3磷酸化的作用。在移植于C57 BL/6小鼠的同基因小鼠刘易斯肺癌（LLC）中，Pt 3显示出比顺铂更高的抗肿瘤活性，且副作用更少。(C)2017 Elsevier Masson SAS。All rights reserved.
New Pt(II) complexes (Pt-1-3) bearing 1,2,5-oxadiazole ligands (1-3) were synthesized, characterized and evaluated for their ability to disrupt STAT3 dimerization. Ligand 3 center dot HC1 showed cytotoxic effects on HCT-116 cells (IC50 = 95.2 mu M) and a selective ability to interact with STAT3 (IC50 = 8.2 mu M) versus STATI (IC50 > 30 mu M). Its corresponding platinum complex Pt -3 exhibited an increased cytotoxicity (IC50 = 18.4 mu M) and a stronger interaction with STAT3 (IC50 = 1.4 mu M), leading to inhibition of its signaling pathway. Pt -3 was also evaluated in cell-based assays for its action on p53 expression and on STAT3 phosphorylation. In syngeneic murine Lewis lung carcinoma (LLC) implanted in C57BL/6 mice, Pt 3 showed a higher antitumor activity with fewer side effects than cisplatin. (C) 2017 Elsevier Masson SAS. All rights reserved.