For investigating reduction of side effects of commercial anticancer drugs, such as cisplatin, three new platinum complexes with glycine derivatives and the formula of [Pt(R-amine)₂(R-gly)]NO₃ were synthesized where R-amine is propylamine, isopentylamine, and tertpentylamine and R-gly is propylglycine, isopentylglycine, and tertpentylglycine, which were characterized by spectroscopic methods, such as ultraviolet–visible, infrared, and proton nuclear magnetic resonance (¹H-NMR) spectroscopy. The in-vitro cytotoxicity of these water-soluble complexes and cisplatin as a controller was assessed against MCF-7 cell line by MTT assay. The 50% inhibitory concentration values showed that the inhibitory effect of propyl derivative was better than the other systems. According to solubility of these compounds in water and also comparing the results of assessing adsorption, distribution, metabolism, and excretion, these compounds can be considered as drug-like molecules and oral medication. Given the density functional theory data, such as electronegativity, nucleophilicity, additional electronic charges, and global softness, anticancer properties of the synthesized complexes were almost similar and predominantly more than the cisplatin. DNA binding modes were evaluated by experimental circular dichroism (CD) spectroscopy, and also theoretical study of molecular docking. CD spectra showed a decrease in the intensity of the positive band and an increase in the negative band indicating formation of DNA-complex electrostatic interaction for positively charged synthesized complexes. CD spectra indicated conversion of B-DNA into A-DNA form via electrostatic interaction for positively charged propyl complex at high concentration. Results of studying molecular docking showed that hydrogen bonding is more effective than other interactions, such as electrostatic and covalent interactions, especially for bulky systems. In this regard, glycine derivatives may reduce the side effects of Pt-drugs in treatment of cancer.

Graphical abstract

Three new anticancer Pt(II) complexes were synthesized with glycine derivatives. In vitro cytotoxicity effects were tested against the human breast cancer cell line of MCF-7. Moreover, the modes of DNA binding with synthesized compounds were investigated using Circular dichroism spectra, ADME prediction, DFT, MEP, and molecular docking.

中文翻译：

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三种具有甘氨酸衍生物的抗癌Pt复合物：合成，对MCF-7细胞系的生物活性，ADME预测，DFT，MEP和分子对接

为了研究减少顺铂等商业抗癌药的副作用，合成了三种新的具有甘氨酸衍生物的铂配合物和[Pt（R-amine）₂（R-gly）] NO _{3的化学式}，其中R-胺为丙胺，异戊基胺，叔戊基胺和R-gly是丙基甘氨酸，异戊基甘氨酸和叔戊基甘氨酸，它们通过光谱方法（例如紫外可见，红外和质子核磁共振）表征（¹1 H-NMR）光谱。通过MTT分析评估了这些水溶性复合物和顺铂作为控制剂对MCF-7细胞系的体外细胞毒性。50％抑制浓度值表明丙基衍生物的抑制作用优于其他体系。根据这些化合物在水中的溶解度，并根据评估吸附，分布，代谢和排泄的结果进行比较，可以将这些化合物视为类药物分子和口服药物。给定密度泛函理论数据，例如电负性，亲核性，额外的电荷和整体柔软性，合成的复合物的抗癌特性几乎相似，并且主要比顺铂更高。通过实验圆二色（CD）光谱评估了DNA结合模式，以及分子对接的理论研究。CD谱显示出正带强度的减小和负带的增加，表明形成带正电荷的合成复合物的DNA-复合物静电相互作用。CD谱表明高浓度带正电荷的丙基配合物通过静电相互作用将B-DNA转化为A-DNA形式。研究分子对接的结果表明，氢键比其他相互作用（例如静电和共价相互作用）更有效，尤其是对于庞大的系统。在这方面，甘氨酸衍生物可以减少Pt药物在癌症治疗中的副作用。CD谱显示出正带强度的减小和负带的增大，表明形成带正电荷的合成复合物的DNA-复合物静电相互作用。CD谱表明高浓度带正电荷的丙基配合物通过静电相互作用将B-DNA转化为A-DNA形式。研究分子对接的结果表明，氢键比其他相互作用（例如静电和共价相互作用）更有效，尤其是对于庞大的系统。在这方面，甘氨酸衍生物可以减少Pt药物在癌症治疗中的副作用。CD谱显示出正带强度的减小和负带的增加，表明形成带正电荷的合成复合物的DNA-复合物静电相互作用。CD谱表明高浓度带正电荷的丙基配合物通过静电相互作用将B-DNA转化为A-DNA形式。研究分子对接的结果表明，氢键比其他相互作用（例如静电和共价相互作用）更有效，尤其是对于庞大的系统。在这方面，甘氨酸衍生物可以减少Pt药物在癌症治疗中的副作用。CD谱表明高浓度带正电荷的丙基配合物通过静电相互作用将B-DNA转化为A-DNA形式。研究分子对接的结果表明，氢键比其他相互作用（例如静电和共价相互作用）更有效，尤其是对于庞大的系统。在这方面，甘氨酸衍生物可以减少Pt药物在癌症治疗中的副作用。CD谱表明高浓度带正电荷的丙基配合物通过静电相互作用将B-DNA转化为A-DNA形式。研究分子对接的结果表明，氢键比其他相互作用（例如静电和共价相互作用）更有效，尤其是对于庞大的系统。在这方面，甘氨酸衍生物可以减少Pt药物在癌症治疗中的副作用。

图形概要

使用甘氨酸衍生物合成了三种新的抗癌Pt（II）复合物。测试了针对人乳腺癌细胞MCF-7的体外细胞毒性作用。此外，使用圆二色光谱，ADME预测，DFT，MEP和分子对接研究了与合成化合物结合的DNA模式。