Kalaivani P, Saranya S, Poornima P, Prabhakaran R, Dallemer F, Vijaya Padma V, Natarajan K
Department of Chemistry, Bharathiar University, Coimbatore 641 046, India.
Department of Biotechnology, Bharathiar University, Coimbatore 641 046, India.
Eur J Med Chem. 2014 Jul 23;82:584-99. doi: 10.1016/j.ejmech.2014.05.075. Epub 2014 Jun 3.
A series of novel nickel(II) thiosemicarbazone complexes(1-4) have been prepared and characterized by various spectral, analytical techniques and X-ray crystallography. Further, their efficacy to interact with CT-DNA/BSA has been explored. From the binding studies, it is inferred that complex 4 found to be more active than other complexes. The complexes bound with CT-DNA by intercalation mode. Moreover, static quenching was observed for their interaction with BSA. The new complexes were tested for their in vitro cytotoxicity against human lung adenocarcinoma (A549) cell line. The results showed that the new complexes exhibited significant degree of cytotoxicity at given experimental condition. Further, the results of LDH and NO release supported the cytotoxic nature of the complexes. The observed cytotoxicity of the complexes may be routed through ROS-hypergeneration and lipid-peroxidation with subsequent depletion of cellular antioxidant pool (GSH, SOD, CAT, GPx and GST) resulted in the reduction of mitochondrial-membrane potential, caspase-3 activation and DNA fragmentation. Thus, the data from the present study disclose that the complexes could induce apoptosis in A549 cells through mitochondrial mediated fashion and inhibited the migration of lung cancer cells and by metastasis.
一系列新型镍（II）硫代氨基脲配合物（1-4）已被制备，并通过各种光谱、分析技术和X射线晶体学进行了表征。此外，还研究了它们与CT-DNA/BSA相互作用的功效。从结合研究中可以推断，发现配合物4比其他配合物更具活性。这些配合物通过插入模式与CT-DNA结合。此外，观察到它们与BSA相互作用时发生静态猝灭。测试了这些新配合物对人肺腺癌（A549）细胞系的体外细胞毒性。结果表明，在给定的实验条件下，新配合物表现出显著程度的细胞毒性。此外，LDH和NO释放的结果支持了配合物的细胞毒性性质。观察到的配合物的细胞毒性可能是通过ROS过度产生和脂质过氧化，随后细胞抗氧化池（GSH、SOD、CAT、GPx和GST）耗竭，导致线粒体膜电位降低、caspase-3激活和DNA片段化。因此，本研究的数据表明，这些配合物可以通过线粒体介导的方式诱导A549细胞凋亡，并抑制肺癌细胞的迁移和转移。
