Physical structure of constitutional isomers influences antiproliferation activity of thiosemicarbazone-alkylthiocarbamate copper complexes
Physical structure of constitutional isomers influences antiproliferation activity of thiosemicarbazone-alkylthiocarbamate copper complexes
复制标题
异构体的物理结构影响缩氨基硫脲-烷基硫代氨基甲酸盐铜配合物的抗增殖活性
DOI：
10.1016/j.jinorgbio.2023.112288
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发表时间：
2023
影响因子：
3.9
通讯作者：
Buchanan, Robert M.
中科院分区：
文献类型：
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作者：
Bajaj, Kritika;Andres, Sarah A.;Hofsommer, Dillon T.;Greene, Aidan F.;Hietsoi, Oleksandr;Mashuta, Mark S.;Weis, Theresa;Beverly, Levi J.;Bates, Paula J.;Buchanan, Robert M.
合成了一系列电子环境相似但物理结构不同的氨基硫脲-烷基硫代氨基甲酸铜杂化配合物，并对其进行了表征和抗增殖活性评价。配合物包括构型异构体(1-phenylpropane-1-imine-(O-ethylthiocarbamato)-2-one-(N-methylthiosemicarbazonato))copper(II)(CuL1)和(1-phenylpropane-1-one-(N-methylthiosemicarbazonato)-2-imine-(O-ethylthiocarbamato))copper(II)(CuL2)以及(1-propane-1-imine-(O-ethylthiocarbamato)-2-one-(N-methylthiosemicarbazonato))copper(II)(Cl3)。配合物CuL1和CuL2在1-苯丙烷主链上的侧基缩氨基硫脲(TSC)和烷基硫代氨基甲酸酯(ATC)的位置不同。与CuL1一样，络合物CuL3采用丙烷主链，TSC处于2-位。CuL1和CuL2具有相同的电子环境，具有难以区分的CuII/I势(e1/2=-0.86V对二茂铁/二茂铁)和电子顺磁共振谱(g∥=2.26，g⊥=2.08)。CuL3的电子结构与CuL1，2的电子结构相似，E_1/2为-0.84V，EPR参数相同。单晶X-射线衍射研究证实，CuL3具有一致的施主环境，络合物之间的Cusingle键N或Cusingle键的键距和键角没有明显变化。用四甲基偶氮唑盐比色法测定了CuL1-3对肺腺癌细胞(A549)和非恶性肺成纤维细胞(IMR-90)的抗增殖活性。CuL1具有最高的A549活性(A549EC50=0.065μM)和选择性(IMR-90EC50/A549EC50=20)。构型异构体CuL2的A549活性(0.18μM)和选择性(10.6)均降低。络合物CuL3的活性(0.009μM)与CuL1相似，但缺乏选择性(1)。用电感耦合等离子体质谱测定的细胞铜负载量与活性和选择性的趋势是一致的。络合物CuL1-3不诱导ROS的产生。
A series of hybrid thiosemicarbazone-alkylthiocarbamate copper complexes with similar electronic environments but distinct physical structures have been prepared, characterized, and evaluated for antiproliferation activity. The complexes include the constitutional isomers (1-phenylpropane-1-imine-(O-ethylthiocarbamato)-2-one-(N-methylthiosemicarbazonato))copper(II) (CuL1) and (1-phenylpropane-1-one-(N-methylthiosemicarbazonato)-2-imine-(O-ethylthiocarbamato))copper(II) (CuL2) along with (1-propane-1-imine-(O-ethylthiocarbamato)-2-one-(N-methylthiosemicarbazonato))copper(II) (CuL3). Complexes CuL1and CuL2differ in the positions of the pendent thiosemicarbazone (TSC) and alkylthiocarbamate (ATC) moieties on the 1-phenylpropane backbone. Complex CuL3employs a propane backbone with the TSC in the 2-position as in CuL1. The isomer pair CuL1and CuL2have equivalent electronic environments with indistinguishable CuII/Ipotentials (E1/2= -0.86 V vs. ferrocenium/ferrocene) and electron paramagnetic resonance (EPR) spectra (g∥= 2.26, g⊥= 2.08). The electronic structure of CuL3has a similarE1/2of -0.84 V and identical EPR parameters to CuL1, 2. Single crystal X-ray diffraction studies confirm a consistent donor environment with no substantial variation in the Cusingle bondN or Cusingle bondS bond distances and angles between the complexes. The antiproliferation activities of the CuL1–3were evaluated against the lung adenocarcinoma cell line (A549) and nonmalignant lung fibroblast cell line (IMR-90) using the MTT assay. CuL1had the highest A549 activity (A549EC50= 0.065 μM) and selectivity (IMR-90EC50/A549EC50= 20). The constitutional isomer CuL2displayed decreased A549 activity (0.18 μM) and selectivity (10.6). The complex CuL3displayed activity (0.009 μM) similar to CuL1but with a lack of selectivity (1.0). Cellular copper loading determined by ICP-MS was consistent with the activity and selectivity trends. The complexes CuL1–3did not induce reactive oxygen species (ROS) generation.