Bioinorganic Lab., Department of Chemistry, Jamia Millia Islamia, New Delhi 110025, India.
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India.
Bioorg Chem. 2019 Jun;87:773-782. doi: 10.1016/j.bioorg.2019.03.080. Epub 2019 Apr 4.
Development of new chemotherapeutic agents to treat microbial infections and recurrent cancers is of pivotal importance. Metal based drugs particularly ruthenium complexes have the uniqueness and desired properties that make them suitable candidates for the search of potential chemotherapeutic agents. In this study, two mixed ligand Ru(III) complexes [Ru(Cl)(SB)(Phen] (RC-1) and [Ru(Cl)(SB)(Bipy)] (RC-2) were synthesised and characterized by elemental analysis, IR, UV-Vis, H, C NMR spectroscopic techniques and their molecular structure was confirmed by X-ray crystallography. Antibacterial activity evaluation against two Gram-positive (S. pneumonia and E. faecalis) and four Gram-negative strains (P. aurogenosa, K. pneumoniae, S. enterica, and E. coli) revealed their moderate antibacterial activity with MIC value of ≥250 μg/mL. Anticancer activity evaluation against a non-small lung cancer cell line (H1299) revealed the tremendous anticancer activity of these complexes which was further validated by DNA binding and docking results. DNA binding profile of the complexes studied by UV-Visible and fluorescence spectroscopy showed an intercalative binding mode with CT-DNA and an intrinsic binding constant in the range of 3.481-1.015× 10 M. Both the complexes were also found to exert weak toxicity to human erythrocytes by haemolytic assay compared to cisplatin. Potential of these complexes as anticancer agents will be further delineated by in vivo studies.
开发新的化疗药物来治疗微生物感染和复发性癌症至关重要。金属基药物，特别是钌配合物具有独特性和所需的特性，使它们成为寻找潜在化疗药物的合适候选物。在这项研究中，合成并通过元素分析、IR、UV-Vis、H、C NMR 光谱技术表征了两种混合配体 Ru(III)配合物[Ru(Cl)(SB)(Phen)]（RC-1）和[Ru(Cl)(SB)(Bipy)]（RC-2），并通过 X 射线晶体学确认了它们的分子结构。对两种革兰氏阳性（肺炎链球菌和粪肠球菌）和四种革兰氏阴性菌株（铜绿假单胞菌、肺炎克雷伯菌、肠炎沙门氏菌和大肠杆菌）的抗菌活性评估表明，它们具有中等的抗菌活性，MIC 值≥250μg/mL。对非小细胞肺癌细胞系（H1299）的抗癌活性评估表明，这些配合物具有巨大的抗癌活性，这一结果进一步通过 DNA 结合和对接结果得到验证。通过紫外可见光谱和荧光光谱研究配合物的 DNA 结合特性表明，它们与 CT-DNA 具有插入结合模式，固有结合常数在 3.481-1.015×10 M 范围内。与顺铂相比，通过溶血试验发现，这两种配合物对人红细胞的毒性也较弱。这些配合物作为抗癌剂的潜力将通过体内研究进一步阐明。
