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3-(2-(2,4-二羟基亚苄基)肼基)喹喔啉-2(1H)-酮过渡金属配合物的结构研究、DNA相互作用及抗癌研究

Structural investigation, DNA interactions and anticancer studies of transition metal complexes of 3-(2-(2, 4-dihydroxy benzylidene) hydrazinyl) quinoxalin-2(1H) -one.

作者信息

Sukanya Panaganti, Reddy Chittireddy Venkata Ramana

机构信息

Department of Chemistry, Vasavi College of Engineering, Hyderabad, India.

Department of Chemistry, Jawaharlal Nehru Technological University Hyderabad, Hyderabad, India.

出版信息

J Biomol Struct Dyn. 2022 Aug;40(13):6151-6162. doi: 10.1080/07391102.2021.1877819. Epub 2021 Jan 29.

DOI:10.1080/07391102.2021.1877819
PMID:33512301
Abstract

The Schiff base ligand, 3-(2-(2, 4-dihydroxybenzylidene) hydrazinyl) quinoxalin-2(1H)-one (RHQO) has been synthesized and characterized by spectral and single crystal X-ray analysis. The Mn(II), Ni(II) and Cu(II) complexes of RHQO have been synthesized and characterized by FT-IR, UV-VIS, mass, EPR spectra, CHN, thermo gravimetric analysis, magnetic susceptibility and conductivity measurements. The morphology of the ligand and complexes is studied by Scanning Electron Microscopy. The metal complexes formed were found to be polymeric in nature. The abilities of the ligand and its metal complexes to interact and bind with calf thymus DNA (CT-DNA) has been studied by electronic absorption spectroscopy and their quantitative binding strength was evaluated in terms of their intrinsic binding constant (K). The cleavage interaction of the ligand and its metal complexes with super coiled pBR 322 DNA has been investigated by agarose gel electrophoresis. Cytotoxicity of the Cu(II) and Ni(II) complexes was evaluated using various cancer cell lines, Human cervical cancer cell line (Hela), B16 melanoma F10(B16-F10), Human ovarian cancer cell (SKOV3) and Breast cancer cell line (MCF7) by MTT assay. The results indicated that the ligand and its metal complexes bind with CT-DNA by groove binding mode and cleaved the supercoiled pBR 322 DNA in to nicked form. The Ni(II) and Cu(II) complexes exhibited anticancer activity without affecting the normal CHO-K1 cell lines. Communicated by Vsevolod Makeev.

摘要

席夫碱配体3-(2-(2,4-二羟基苄叉基)肼基)喹喔啉-2(1H)-酮(RHQO)已通过光谱和单晶X射线分析进行了合成和表征。RHQO的Mn(II)、Ni(II)和Cu(II)配合物已通过傅里叶变换红外光谱(FT-IR)、紫外可见光谱(UV-VIS)、质谱、电子顺磁共振光谱(EPR)、CHN、热重分析、磁化率和电导率测量进行了合成和表征。通过扫描电子显微镜研究了配体和配合物的形态。发现形成的金属配合物本质上是聚合物。通过电子吸收光谱研究了配体及其金属配合物与小牛胸腺DNA(CT-DNA)相互作用和结合的能力,并根据其固有结合常数(K)评估了它们的定量结合强度。通过琼脂糖凝胶电泳研究了配体及其金属配合物与超螺旋pBR 322 DNA的切割相互作用。使用人宫颈癌细胞系(Hela)、B16黑色素瘤F10(B16-F10)、人卵巢癌细胞(SKOV3)和乳腺癌细胞系(MCF7)等多种癌细胞系,通过MTT法评估了Cu(II)和Ni(II)配合物的细胞毒性。结果表明,配体及其金属配合物通过沟槽结合模式与CT-DNA结合,并将超螺旋pBR 322 DNA切割成切口形式。Ni(II)和Cu(II)配合物表现出抗癌活性,而不影响正常的CHO-K1细胞系。由Vsevolod Makeev传达。

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