Molecular Diversity ( IF 3.9 ) Pub Date : 2021-09-24 , DOI: 10.1007/s11030-021-10317-0 Darshana N Kanthecha 1, 2 , Bhupesh S Bhatt 1 , Mohan N Patel 1 , Foram U Vaidya 3 , Chandramani Pathak 4
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Pyrazine-bipyrazole-based µ-oxo bridged dinuclear Au(III) complexes were synthesized and characterized by various spectrometric (1H-NMR, 13C (APT) NMR, FT-IR, Mass spectrometry) and analytical techniques (elemental analysis and conductance measurement). The evaluation of DNA binding activity by UV–Vis absorption spectra and viscosity measurement demonstrated that all the compounds intercalate in between the stacks of DNA base pair and the binding constant values were observed in the range of 5.4 × 104–2.17 × 105 M−1. The molecular docking study also supports the intercalation mode of binding. The anti-proliferation activity of complexes on A549 (Lung adenocarcinoma) cells by MTT assay demonstrated IC50 values in the range of 47.46 -298.12 μg/mL. The genotoxicity of compounds was checked by smearing observed in the DNA of S. pombe cell under the influence of complexes. The in vivo cytotoxicity of compounds against brine shrimp demonstrated the LC50 values in the range of 4.59–27.22 μg/mL. The promising results of the Au(III) complexes received significant attention and make them suitable for the new metallodrugs after the detailed mechanistic biological study.
Graphic abstract
中文翻译：
DNA 相互作用、抗癌、细胞毒性和基因毒性研究与潜在的吡嗪-联吡唑双核 µ-氧代桥接 Au(III) 配合物
合成了基于吡嗪-联吡唑的 µ-氧桥双核 Au(III) 配合物，并通过各种光谱（1 H-NMR、13 C (APT) NMR、FT-IR、质谱）和分析技术（元素分析和电导）进行了表征测量）。通过紫外-可见吸收光谱和粘度测量对 DNA 结合活性的评估表明，所有化合物都插入在 DNA 碱基对的堆叠之间，并且观察到的结合常数值在 5.4 × 10 4 –2.17 × 10 5 M范围内-1。分子对接研究也支持嵌入结合模式。通过 MTT 法检测复合物对 A549（肺腺癌细胞）细胞的抗增殖活性证明了 IC50 个值在 47.46 -298.12 μg/mL 范围内。在复合物的影响下，通过在粟酒裂殖酵母细胞的 DNA 中观察到的涂片检查化合物的遗传毒性。化合物对盐水虾的体内细胞毒性表明 LC 50值在 4.59–27.22 μg/mL 范围内。Au(III) 配合物的良好结果受到了广泛关注，经过详细的机理生物学研究，使其适用于新的金属药物。
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