Department of Chemistry, Faculty of Science, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran.
Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences, Tehran, Iran.
Bioorg Chem. 2021 Oct;115:105193. doi: 10.1016/j.bioorg.2021.105193. Epub 2021 Jul 23.
In this study, four novel phosphoramide ligands (L1-L4) are synthesized and characterized by PNMR, HNMR, MASS, and FT-IR spectroscopies. In vitro cell growth inhibition is studied by the MTT assay to evaluate the cytotoxicity of ligands against MCF-7 cell line; the result of the assay demonstrates that all ligands significantly suppress the proliferation of breast cancer cells in a concentration-dependent manner. The calculated IC values are in the range of 3.6-10.77 µg ml, of which the lowest value is attributed to L1. Then a facile approach was developed to functionalize graphene oxide (GO) surface by L1. The data which are obtained by XRD, FT-IR, and EDX analysis confirmed the deposition of phosphoramide on the surface of GO. The cell viability of GO-L1 compound at different concentrations is investigated in 24 h experiment. Excellent synergistic antitumor effects of GO and L1 lead to a decrease in IC value up to 2.13 μg ml. The Quantum calculations of compounds are used to study energies and HOMO and LUMO values, dipole moments (µ), global hardness (η), global softness (σ), and electrophilicity index (ω) using DMol module in Material studio2017. The docking calculations are performed to describe the mode of the binding to DNA and DNA polymerase IIα. Adsorption calculations of ligands (L1-L4) on GO sheet in the presence of water showed that L1 and L2 were located on GO via π electrons of anisole ring. While, L3 and L4 were located on GO by π - π interactions of aniline ring.
在这项研究中，合成了四个新的膦酰胺配体（L1-L4），并通过 PNMR、HNMR、MASS 和 FT-IR 光谱进行了表征。通过 MTT 测定法研究了体外细胞生长抑制作用，以评估配体对 MCF-7 细胞系的细胞毒性；该测定的结果表明，所有配体均以浓度依赖的方式显著抑制乳腺癌细胞的增殖。计算出的 IC 值范围为 3.6-10.77μg/ml，其中最低值归因于 L1。然后，开发了一种简便的方法，通过 L1 对氧化石墨烯（GO）表面进行功能化。通过 XRD、FT-IR 和 EDX 分析获得的数据证实了膦酰胺在 GO 表面的沉积。在 24 小时实验中研究了不同浓度下 GO-L1 化合物的细胞活力。GO 和 L1 的协同抗肿瘤作用非常出色，导致 IC 值降低至 2.13μg/ml。使用 Material studio2017 中的 DMol 模块对化合物进行量子计算，以研究能量和 HOMO 和 LUMO 值、偶极矩（µ）、全局硬度（η）、全局软度（σ）和电亲性指数（ω）。进行对接计算以描述与 DNA 和 DNA 聚合酶 IIα 的结合模式。在存在水的情况下，对配体（L1-L4）在 GO 片上的吸附计算表明，L1 和 L2 通过苯甲醚环的π 电子位于 GO 上。而 L3 和 L4 通过苯胺环的π-π 相互作用位于 GO 上。
