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关于3-乙酰基-7-甲氧基香豆素席夫碱及其具有强抗增殖活性以及增强的乳酸脱氢酶(LDH)和一氧化氮(NO)释放的钌(II)金属配合物的研究。

An investigation on 3-acetyl-7-methoxy-coumarin Schiff bases and their Ru(ii) metallates with potent antiproliferative activity and enhanced LDH and NO release.

作者信息

Kalaiarasi G, Jeya Rajkumar S Rex, Dharani S, Małecki J G, Prabhakaran R

机构信息

Department of Chemistry, Bharathiar University Coimbatore 641 046 India

Department of Biosciences and Technology, Karunya University Coimbatore 641 114 India.

出版信息

RSC Adv. 2018 Jan 4;8(3):1539-1561. doi: 10.1039/c7ra12104k. eCollection 2018 Jan 2.

Abstract

New cyclometallated ruthenium(ii) complexes of 3-acetyl-7-methoxycoumarin-4-substituted thiosemicarbazones were synthesized and characterized by analytical and spectral techniques. The crystal structures of the ligands HL and complexes (1, 2 and 4) were confirmed by X-ray crystallography. The analysis showed that the ligands have undergone C-H activation at the C(4) carbon of the pyrone ring and acted in a tridentate fashion by binding through C, N and S atoms. CT-DNA and protein (BSA/HSA) binding studies were carried out to analyze their interaction with biomolecules. Good binding affinity with DNA was observed with intercalative binding mode, which was further confirmed by EB displacement and viscosity measurement studies. The quenching mechanism with BSA/HSA was found to be static. Three dimensional (3D) fluorescence measurements were carried out to validate the micro environmental changes in the serum albumins. Their antioxidant propensity and antimicrobial study insisted that the compounds displayed good spectrum of activity. Evaluation of their anticancer potential against MCF-7 (human breast cancer) and A549 (human lung carcinoma) cell lines revealed that the complexes exhibited better activity than the ligands and cisplatin. Further, the results of LDH and NO release assays supported the cytotoxic nature of the compounds. The non-toxic nature of the compounds was established by testing against the non-cancerous cell line HaCaT (human normal keratinocyte).

摘要

合成了3-乙酰基-7-甲氧基香豆素-4-取代硫代半卡巴腙的新型环金属化钌(II)配合物,并通过分析和光谱技术对其进行了表征。通过X射线晶体学确定了配体HL和配合物(1、2和4)的晶体结构。分析表明,配体在吡喃酮环的C(4)碳处发生了C-H活化,并通过C、N和S原子以三齿方式配位。进行了CT-DNA和蛋白质(BSA/HSA)结合研究,以分析它们与生物分子的相互作用。观察到与DNA具有良好的结合亲和力,结合模式为插入式,EB位移和粘度测量研究进一步证实了这一点。发现与BSA/HSA的猝灭机制是静态的。进行了三维(3D)荧光测量,以验证血清白蛋白中的微观环境变化。它们的抗氧化倾向和抗菌研究表明这些化合物具有良好的活性谱。评估它们对MCF-7(人乳腺癌)和A549(人肺癌)细胞系的抗癌潜力,结果显示配合物比配体和顺铂表现出更好的活性。此外,LDH和NO释放测定的结果支持了这些化合物的细胞毒性性质。通过对非癌细胞系HaCaT(人正常角质形成细胞)进行测试,确定了这些化合物的无毒性质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f03/9077138/1a81d8c8caab/c7ra12104k-s1.jpg

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