为了发现新的抗癌药物，我们合成了新型钌(III)络合物[Ru(L)Cl(H2O)]，其中L为四齿席夫碱双(乙酰丙酮)乙二胺(im 与acacen, 1)、双(苯甲酰丙酮)乙二胺(bzacen, 2)、(乙酰丙酮)(苯甲酰丙酮)乙二胺(acacbzacen, 3)、双(乙酰丙酮)丙二胺(acacpn, 4)、双(苯甲酰丙酮)丙二胺(bzacpn, 5)或(乙酰丙酮)(苯甲酰丙酮)丙二胺(acacbzacpn, 6)。利用元素分析、摩尔电导、以及紫外-可见光谱、红外光谱、电子顺磁共振、和电喷雾质谱等多种光谱技术对1 - 6进行了表征。根据体外DNA/BSA实验，具有两个芳环的络合物2(bzacen)和5(bzacpn)表现出最高的DNA/BSA活性，表明四齿席夫碱配体上芳环的存在有助于增加活性。此外，这两个化合物对人体A549和小鼠LLC1肺癌细胞表现出最高的细胞毒作用。这些络合物改变了抗凋亡分子和促凋亡分子的比例，并诱导了A549细胞的凋亡。此外，络合物2和5减少了Mcl1和Bcl2在LLC1细胞中的表达比例，诱导了它们的凋亡死亡，并对LLC1细胞产生了抑制增殖的效果。最后，络合物5减少了小鼠原发异位Lewis肺癌的体积，而络合物2降低了肺部转移的发生率和平均数。此外，与DNA的分子对接显示，芳环数目减少或消失会导致络合物间层合性质降低，顺序为：2 > 5 > 6 > 3 > 4 > 1。观察到常规氢键和疏水相互作用有助于络合物-DNA结构的稳定。与BSA的分子对接研究显示，1 - 6在第三D形状亚域IB内的活性位点III中，其结合能力以1为主。版权所有 © 2023 Elsevier Inc.。保留所有权利。

In order to discover new anticancer drugs, novel ruthenium(III) complexes [Ru(L)Cl(H2O)], where L is tetradentate Schiff base bis(acetylacetone)ethylendiimine (acacen, 1), bis(benzoylacetone)ethylendiimine (bzacen, 2), (acetylacetone)(benzoylaceton)ethylendiimine (acacbzacen, 3), bis(acetylacetone)propylendiimine (acacpn, 4), bis(benzoylacetone)propylendiimine (bzacpn, 5) or (acetylacetone)(benzoylaceton)propylendiimine (acacbzacpn, 6), were synthesized. The complexes 1 - 6 were characterized by elemental analysis, molar conductometry, and by various spectroscopic techniques, such as UV-Vis, IR, EPR, and ESI-MS. Based on in vitro DNA/BSA experiments, complexes 2 (bzacen) and 5 (bzacpn) with two aromatic rings showed the highest DNA/BSA-activity, suggesting that the presence of the aromatic ring on the tetradentate Schiff base ligand contributes to increased activity. Moreover, these two compounds showed the highest cytotoxic effects toward human, A549 and murine LLC1 lung cancer cells. These complexes altered the ratio of anti- and pro-apoptotic molecules and induced apoptosis of A549 cells. Further, complexes 2 and 5 reduced the percentage of Mcl1 and Bcl2 expressing LLC1 cells, induced their apoptotic death and exerted an antiproliferative effect against LLC1. Finally, complex 5 reduced the volume of mouse primary heterotopic Lewis lung cancer, while complex 2 reduced the incidence and mean number of metastases per lung. Additionally, molecular docking with DNA revealed that the reduced number of aromatic rings or their absence causes lower intercalative properties of the complexes in order: 2 > 5 > 6 > 3 > 4 > 1. It was observed that conventional hydrogen bonds and hydrophobic interactions contribute to the stabilization of the structures of complex-DNA. A molecular docking study with BSA revealed a predominance of 1 - 6 in binding affinity to the active site III, a third D-shaped hydrophobic pocket within subdomain IB.Copyright © 2023 Elsevier Inc. All rights reserved.