Department of Chemistry, Semnan University, Semnan, Iran.
Chemistry & Chemical Engineering Research Center of Iran, Tehran, Iran.
J Biol Inorg Chem. 2021 May;26(2-3):283-298. doi: 10.1007/s00775-021-01851-1. Epub 2021 Feb 22.
In this study, two new anticancer platinum complexes formulated as [Pt(bpy)(L)]NO were synthesized using the iso and tert-pentylglycine ligands, two structural isomer ligands, to investigate side branches effect on the complex-DNA interaction. According to the comparative results of the ADMET assessment, these compounds can be considered as the drug-like molecules and oral medication. Mechanism of tumor inhibition and DNA binding parameters indicated the higher ability of the tert-isomer and also, both complexes acted through the disruption of the base pairs and stacks of helicity by the endothermic process. Fluorescence spectroscopy showed that the quenching mechanism is static for both drugs with large binding constant and high binding affinity towards the DNA. Also, the amount of binding constant of the tert -isomer was about 14 times of another structural isomerous complex. CD spectra indicated the conversion of the B-DNA into A-DNA form via electrostatic interaction for positively charged complexes. The cytotoxic data showed that both compounds have antiproliferative effects against the MCF-7 cell line and the inhibitory effect of the iso-derivative was better than the tert-one. Docking studies showed that the desolvation energy and hydrogen bond are more effective between the other interactions. The torsional free energy for both complexes mainly provided the groove binding along with partially electrostatic and intercalate binding. According to the density-functional theory data and because of positive electron density on the surface of complexes and facilitating of the metal drug to DNA phosphate groups approaching, both complexes may be good candidates for the anticancer drugs. Two 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 ADME prediction, DFT, molecular docking and spectroscopic methods.
在这项研究中，使用异戊基和叔戊基甘氨酸这两种结构异构体配体制备了两种新的抗癌铂配合物[Pt(bpy)(L)]NO，以研究侧链对配合物-DNA 相互作用的影响。根据 ADMET 评估的比较结果，这些化合物可以被认为是类药性分子和口服药物。肿瘤抑制机制和 DNA 结合参数表明叔异构体的能力更高，并且两种配合物都通过内吸过程破坏碱基对和螺旋堆积起作用。荧光光谱表明，两种药物的猝灭机制都是静态的，具有较大的结合常数和对 DNA 的高结合亲和力。此外，叔异构体的结合常数约为另一种结构异构体复合物的 14 倍。CD 光谱表明，通过静电相互作用，正电荷配合物将 B-DNA 转化为 A-DNA 形式。细胞毒性数据表明，两种化合物对 MCF-7 细胞系均具有抗增殖作用，且同系物衍生物的抑制作用优于叔异构体。对接研究表明，去溶剂化能和氢键在其他相互作用中更有效。两种配合物的扭转自由能主要提供沿沟结合，部分提供静电和嵌入结合。根据密度泛函理论数据，由于配合物表面的正电子密度以及金属药物与 DNA 磷酸基团接近的促进作用，这两种配合物可能是潜在的抗癌药物。用甘氨酸衍生物合成了两种新型抗癌铂（II）配合物。体外细胞毒性作用通过 MCF-7 人乳腺癌细胞系进行测试。此外，还通过 ADME 预测、DFT、分子对接和光谱方法研究了合成化合物与 DNA 的结合模式。
