Department of Chemistry, Science and Research branch, Islamic Azad University, Tehran, Iran.
Chemistry & Chemical Engineering Research Center of Iran, Tehran, Iran.
Appl Biochem Biotechnol. 2018 Oct;186(2):271-291. doi: 10.1007/s12010-018-2715-5. Epub 2018 Mar 8.
Methylglycine, also known sarcosine, is dramatically used in drug molecules and its metal complexes can interact to DNA and also do cleavage. Hence, to study the influence of methylglycine ligand on biological behavior of metal complexes, two water-soluble platinum (II) complexes with the formula cis-[Pt(NH)(CH-gly)]NO and cis-[Pt(NH-CH)(CH-gly)]NO (where CH-gly is methylglycine) have been synthesized and characterized by spectroscopic methods, molar conductivity measurements, and elemental analyzes. The anticancer activity of synthesized complexes was tested against human breast adenocarcinoma cell line of MCF7 using MTT assay and results showed excellent anticancer activity with Cc values of 126 and 292 μM after 24 h incubation time, for both complexes of cis-[Pt(NH)(CHgly)]NO and cis-[Pt(NH-CH)(CHgly)]NO, respectively. Also, the interaction between Pt(II) complexes with calf thymus DNA was extensively studied by means of absorption spectroscopy, fluorescence titration spectra displacement with ethidium bromide (EtBr), and circular dichroism studied in Tris-buffer. The obtained spectroscopic results revealed that two complexes can bind to highly polymerized calf thymus DNA cooperatively and denature at micromolar concentrations. The fluorescence data indicate that quenching effect for cis-[Pt(NH)(CHgly)]NO (K = 9.48 mM) was higher than that of cis-[Pt(NH-CH)(CHgly)]NO (K 1.98 mM). These results were also confirmed by circular dichrosim spectra. Consequently, docking data showed that cis-[Pt(NH)(CHgly)]NO with more interaction energy binds on DNA via groove binding which is more compatible with experimental results. Graphical Abstract ᅟ Two anticancer Pt(II) complexes, cis-[Pt(NH)(CHgly)]NO and cis-[Pt(NHCH)(CHgly)]NO, have been synthesized and interacted with calf thymus DNA. Improving solubility of these compounds reduce side effects and increase anticancer activity against human breast cell line. Modes of binding have been studied by electronic absorption, fluorescence, and CD measurements. Results show that both Pt(II) complexes can interact to DNA via groove binding.
甲基甘氨酸，也称为肌氨酸，在药物分子中被广泛应用，其金属配合物可以与 DNA 相互作用并进行切割。因此，为了研究甲基甘氨酸配体对金属配合物生物行为的影响，我们合成并通过光谱法、摩尔电导率测量和元素分析对两个具有式 cis-[Pt(NH)(CH-gly)]NO 和 cis-[Pt(NH-CH)(CH-gly)]NO（其中 CH-gly 是甲基甘氨酸）的水溶性铂（II）配合物进行了表征。我们使用 MTT 测定法测试了合成配合物对人乳腺癌 MCF7 细胞系的抗癌活性，结果表明，两种配合物 cis-[Pt(NH)(CHgly)]NO 和 cis-[Pt(NH-CH)(CHgly)]NO 的 Cc 值分别为 126 和 292 μM，在 24 小时孵育时间后表现出优异的抗癌活性。此外，还通过吸收光谱、与溴化乙锭（EtBr）的荧光滴定光谱位移以及在 Tris 缓冲液中的圆二色性研究了 Pt(II)配合物与小牛胸腺 DNA 的相互作用。获得的光谱结果表明，两种配合物可以协同结合到高度聚合的小牛胸腺 DNA 上，并在微摩尔浓度下使 DNA 变性。荧光数据表明，cis-[Pt(NH)(CHgly)]NO（K=9.48 mM）的猝灭效应高于 cis-[Pt(NH-CH)(CHgly)]NO（K=1.98 mM）。这些结果也通过圆二色性光谱得到了证实。因此，对接数据表明，与 DNA 通过沟结合的具有更高相互作用能的 cis-[Pt(NH)(CHgly)]NO 更符合实验结果。
