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一种 ONS 供体连接铜(II)配合物的有效药物候选物:抗癌活性、细胞毒性和通过光谱法研究与 BSA 的结合。

Potent drug candidature of an ONS donor tethered copper (II) complex: Anticancer activity, cytotoxicity and spectroscopically approached BSA binding studies.

机构信息

Centre for Nano and Material Sciences, JAIN (Deemed-to-be University), Jain Global Campus, Bengaluru, 562112, Karnataka, India.

National Agri Food Biotechnology Institute, Mohali 140306, India.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2019 Apr 5;212:330-342. doi: 10.1016/j.saa.2019.01.020. Epub 2019 Jan 15.

Abstract

In our continued efforts to develop metal based therapeutic agents, we have synthesized a novel copper(II) complex, [{Cu(hpdbal-sbdt)}] (2) tethered with a biocompatible ONS donor backbone [Hhpdbal-sbdt] (1) [Hhpdbal-sbdt is a tridentate ligand derived from S-benzyldithiocarbazate (Hsbdt) and 2-hydroxy-5-(phenyldiazenyl)benzaldehyde (Hhpdbal)]. The metal complex (2) was characterized using attenuated total reflection-infrared (ATR-IR) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, thermogravimetry and differential scanning calorimetric (TG-DSC) analysis, field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS) and elemental (CHNS) analysis. The antineoplastic ability of copper complex was evaluated in vitro against human cervical cancer (HeLa) cells. MTT assay results showed that the copper complex exhibited significant growth inhibition of HeLa cells with an IC value of 4.46 μM and this value was compared with reported standards. Cytotoxicity of the copper complex towards human embryonic kidney cells (HEK-293) was also evaluated. The potentially active copper complex was studied for its solution state stability at a pH range of 3-9. Following this, the interactive behaviour of the bioactive copper complex with a drug transporter protein (BSA) was deciphered through multi-spectrosopic investigations like steady-state fluorescence, three-dimensional fluorescence, deconvoluted-IR and UV-Visible techniques.

摘要

在我们不断努力开发基于金属的治疗剂的过程中,我们合成了一种新型的铜(II)配合物,[{Cu(hpdbal-sbdt)}](2)与生物相容性的 ONS 供体骨架[Hhpdbal-sbdt](1)[Hhpdbal-sbdt 是一种由 S-苄基二硫代氨基甲酸盐(Hsbdt)和 2-羟基-5-(苯基亚氨基)苯甲醛(Hhpdbal)衍生的三齿配体]相连。使用衰减全反射红外(ATR-IR)光谱、电子顺磁共振(EPR)光谱、热重分析和差示扫描量热法(TG-DSC)分析、场发射扫描电子显微镜(FESEM)、能谱(EDS)和元素(CHNS)分析对金属配合物(2)进行了表征。体外评估了铜配合物对人宫颈癌(HeLa)细胞的抗肿瘤活性。MTT 测定结果表明,铜配合物对 HeLa 细胞具有显著的生长抑制作用,IC 值为 4.46 μM,与报道的标准值进行了比较。还评估了铜配合物对人胚肾细胞(HEK-293)的细胞毒性。研究了潜在活性铜配合物在 pH 值为 3-9 的溶液状态下的稳定性。在此之后,通过稳态荧光、三维荧光、去卷积红外和紫外-可见技术等多光谱研究,揭示了生物活性铜配合物与药物转运蛋白(BSA)的相互作用行为。

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