Abstract：
Synthesis of non-platinum transition metal complexes with N,O donor chelating ligand for application against pathogenesis of cancer with higher efficacy and selectivity is currently an important field of research. We assessed the anti-cancer effect of a mixed ligand Ni(II) complex on human breast and lung cancer cell lines in this investigation. Mononuclear mixed ligand octahedral Ni(II) complex [NiIIL(NO3)(MeOH)] complex (1), with tri-dentate phenol-based ligand 2,4-dichloro-6-((4-methylpiperazin-1-yl) methyl) phenol (HL) along with methanol and nitrate as ancillary ligand was prepared. Piperazine moiety of the ligand exists as boat conformation in this complex as revealed from single crystal X-ray study. UV-visible spectrum of complex (1) exhibits three distinct d-d bands due to spin-allowed 3 A2 g→3T1 g (P), 3 A2 g→3T1 g(F) and 3 A2 g→3T2 g(F) transitions as expected in an octahedral d8 system. Our study revealed that Complex (1) induces apoptotic cell death in mouse and human cancer cells such as mcf-7, A549 and MDA-MB-231 through transactivation of p53 and its pro-apoptotic downstream targets in a dose dependent manner. Furthermore, complex (1) was able to slow the migratory rate of MDA-MB-231 cells\' in vitro as well as epithelia -mesenchymal transition (EMT), the key step for metastatic transition and malignancy. Over all our results suggest complex (1) as a potential agent in anti-tumor treatment regimen showing both cytotoxic and anti-metastatic activity against malignant neoplasia.
摘要：
非铂过渡金属配合物的合成与N,O供体螯合配体应用于抗癌具有较高的效力和选择性是今朝一个主要的研讨范畴。在目前的研究中，我们评估了混合配体Ni（II）配合物对人乳腺癌和肺癌细胞系的抗癌作用。单核混合配体八面体Ni（II）配合物[NiIIL（NO3）（MeOH）]配合物（1），以三齿酚基配体2,4-二氯-6-（（4-甲基哌嗪-1-基）甲基）苯酚（HL）以及甲醇和硝酸盐作为辅助配体。从单晶X射线研究中可以看出，配体的哌嗪部分以船形构象存在于该配合物中。由于自旋允许的3A2g→3T1g（P），络合物（1）的紫外可见光谱显示出三个不同的d-d带，3A2g→3T1g（F）和3A2g→3T2g（F）过渡为预期的八面体d8系统。复合物(1)通过p53的反式激活及其促凋亡下游靶标以剂量依赖性方式诱导小鼠和人类癌细胞如mcf-7、A549和MDA-MB-231的凋亡细胞死亡。此外，复合物（1）能够减缓MDA-MB-231细胞的体外迁移速率以及上皮-间质转化（EMT），转移转移和恶性肿瘤的关键步骤。在所有我们的结果表明复合物（1）作为抗肿瘤治疗方案中的潜在药物，同时作为针对恶性肿瘤的细胞毒性和抗转移剂。
