含嘧啶骨架配体的生物活性铂配合物：DNA/BSA 结合、分子对接、抗癌、抗氧化和抗菌活性。

Bioactive platinum complex of ligand bearing pyrimidine skeleton: DNA/BSA binding, molecular docking, anticancer, antioxidant and antimicrobial activities.

机构信息

Department of Chemistry, The American College, Tallakkulam, Madurai, Tamil Nadu, India.

Laboratory of Inorganic Synthesis and Bioinspired Catalysis, Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, India.

出版信息

J Biomol Struct Dyn. 2022 Sep;40(15):6683-6696. doi: 10.1080/07391102.2021.1889667. Epub 2021 Feb 26.

DOI:10.1080/07391102.2021.1889667

PMID:33634734

Abstract

A new octahedral platinum complex [PtLCl] of Schiff base ligand containing pyrimidine and morpholine skeleton (where, L is 4,6-dichloropyrimidin-5-yl)methylene)-2-morpholinoethanamine) was isolated and characterized by elemental analysis, H-NMR, FTIR, UV-visible and ESI-MS techniques. DNA interaction of isolated compounds with calf thymus (CT-DNA) was explored by UV-vis absorption, fluorescence, cyclic voltametric and viscometric methods. The result shows that prepared compounds can interact with CT-DNA through electrostatic interactions. Bovine serum album (BSA) binding behavior of isolated compounds was also studied by UV-vis absorption and fluorescence techniques. Both the spectroscopic results suggest that the isolated ligand and its complex bind with BSA through static quenching. The optimized structure of ligand and platinum complex were achieved by the DFT calculations. Moreover, molecular docking of ligand and its complex were studied. These analysis results reveal that ligand has low binding affinity on DNA and BSA molecules in contrast to its complex. In vitro anticancer activity of isolated compounds toward normal cell line (NHDF) as well as cancer cell lines (MCF-7, HepG2, HeLa and A549) was studied by MTT assay. The results supports that isolated platinum complex can control the growth of cancer cells (MCF-7, 20.12 ± 1.00 µg/mL; HepG2, 32.2 ± 1.69 µg/mL; HeLa, 24.68 ± 1.29 µg/mL; A549, 23.46 ± 1.17 µg/mL) without inhibiting the normal cell line (NHDF, 109.26 ± 5.46 µg/mL). Antioxidant and antimicrobial activities of isolated compounds indicate that ligand and Pt complex are found to have good radical scavenging against four different free radicals and antimicrobial abilities on and antimicrobial species. HighlightsPlatinum complex of Schiff base with pyrimidine and morpholine linkage was synthesized.Pt complex has better biomolecular interaction with DNA and BSA.Molecular docking of Pt complex with DNA and BSA has been studiedPt complex has good anticancer activities.Pt complex has better antioxidant and antimicrobial activities.

摘要

一个新的八面体铂配合物[PtLCl]的席夫碱配体含有嘧啶和吗啉骨架（其中，L 是 4,6-二氯嘧啶-5-基）亚甲基）-2-吗啉乙胺）被分离并通过元素分析、H-NMR、FTIR、UV-可见和 ESI-MS 技术进行了表征。通过紫外可见吸收、荧光、循环伏安和粘度方法研究了分离化合物与小牛胸腺（CT-DNA）的 DNA 相互作用。结果表明，所制备的化合物可以通过静电相互作用与 CT-DNA 相互作用。还通过紫外可见吸收和荧光技术研究了分离化合物与牛血清白蛋白（BSA）的结合行为。光谱结果表明，分离的配体及其配合物通过静态猝灭与 BSA 结合。通过 DFT 计算得到了配体和铂配合物的优化结构。此外，还研究了配体及其配合物的分子对接。这些分析结果表明，与配合物相比，配体对 DNA 和 BSA 分子的结合亲和力较低。通过 MTT 法研究了分离化合物对正常细胞系（NHDF）以及癌细胞系（MCF-7、HepG2、HeLa 和 A549）的体外抗癌活性。结果表明，分离的铂配合物可以控制癌细胞（MCF-7，20.12±1.00μg/mL；HepG2，32.2±1.69μg/mL；HeLa，24.68±1.29μg/mL；A549，23.46±1.17μg/mL）的生长，而不抑制正常细胞系（NHDF，109.26±5.46μg/mL）。分离化合物的抗氧化和抗菌活性表明，配体和 Pt 配合物对四种不同自由基具有良好的自由基清除能力，对和抗菌物种具有抗菌能力。亮点合成了具有嘧啶和吗啉键的席夫碱的铂配合物。Pt 配合物与 DNA 和 BSA 的生物分子相互作用更好。研究了 Pt 配合物与 DNA 和 BSA 的分子对接。Pt 配合物具有良好的抗癌活性。Pt 配合物具有更好的抗氧化和抗菌活性。