Junaid Ahmad, Ng Chew Hee, Ooi Ing Hong
Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia.
ACS Omega. 2022 Jul 19;7(30):26190-26200. doi: 10.1021/acsomega.2c01858. eCollection 2022 Aug 2.
The aim of this study was to synthesize and characterize a nanogold-{[(Cu)(phen)(cys)(HO)]NO} conjugate and to evaluate its antiproliferative property against the breast cancer cell line (MCF7) and normal cell line (MCF10A). Nanogold solution was prepared using the Turkevich method. In one approach, a ternary copper(II) complex of 1,10-phenanthroline with l-cysteine, [(Cu)(phen)(cys)(HO)]NO, was first prepared and then tethered with the gold nanoparticles. In another approach, gold nanoparticles were reacted with l-cysteine, copper(II) nitrate, and 1,10-phenanthroline subsequently. The synthesized [(Cu)(phen)(cys)(HO)]NO complex was characterized by Fourier transform infrared (FTIR) and electrospray ionization mass spectrometry techniques, which showed that l-cysteine was bound to the copper through carboxylic and amino groups, with the thiol moiety remaining free. The free thiol group was bound to the nanogold surface to form the nanogold-{[(Cu)(phen)(cys)(HO)]NO} conjugate, as evidenced by the increase in the surface plasmon absorption band in ultraviolet-visible and the absence of a thiol peak in FTIR of the nanogold-copper complex conjugate. The anticancer activity of the nanogold-copper complex conjugate and the free copper complex against a breast cancer cell line (MCF7) and their toxicity on a normal cell line (MCF10A) were examined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2-tetrazolium assay. Results suggested that the nanogold-{[(Cu)(phen)(cys)(HO)]NO} conjugate demonstrates a selective antiproliferative and proapoptotic effect on the breast cancer cells, confirming the potential of the nanogold-copper complex conjugate as an anticancer agent.
本研究的目的是合成并表征纳米金-{[(铜)(邻菲罗啉)(半胱氨酸)(水)]硝酸盐}共轭物,并评估其对乳腺癌细胞系(MCF7)和正常细胞系(MCF10A)的抗增殖特性。采用Turkevich法制备纳米金溶液。一种方法是,首先制备1,10-邻菲罗啉与L-半胱氨酸的三元铜(II)配合物[(铜)(邻菲罗啉)(半胱氨酸)(水)]硝酸盐,然后将其与金纳米颗粒连接。另一种方法是,金纳米颗粒随后与L-半胱氨酸、硝酸铜(II)和1,10-邻菲罗啉反应。通过傅里叶变换红外(FTIR)和电喷雾电离质谱技术对合成的[(铜)(邻菲罗啉)(半胱氨酸)(水)]硝酸盐配合物进行表征,结果表明L-半胱氨酸通过羧基和氨基与铜结合,硫醇部分保持游离。游离硫醇基团与纳米金表面结合形成纳米金-{[(铜)(邻菲罗啉)(半胱氨酸)(水)]硝酸盐}共轭物,这通过紫外可见光谱中表面等离子体吸收带的增加以及纳米金-铜配合物共轭物的FTIR中硫醇峰的缺失得到证实。使用3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺基苯基)-2-四唑𬭩测定法检测纳米金-铜配合物共轭物和游离铜配合物对乳腺癌细胞系(MCF7)的抗癌活性及其对正常细胞系(MCF10A)的毒性。结果表明,纳米金-{[(铜)(邻菲罗啉)(半胱氨酸)(水)]硝酸盐}共轭物对乳腺癌细胞具有选择性抗增殖和促凋亡作用,证实了纳米金-铜配合物共轭物作为抗癌剂的潜力。