| 含吡啶侧链蒽腙-铜配合物的合成、晶体结构、抗肿瘤活性及DNA键合 | |
| Copper complexes of anthrahydrazone bearing pyridyl side chain: Synthesis, crystal structure, anticancer activity, and DNA binding | |
| 摘要: 为拓展研究蒽环类抗癌药物衍生物的结构和活性并降低其毒副作用，设计合成了一类新的蒽腙类衍生物：9-吡啶蒽腙(9-PAH)和9，10-双吡啶蒽腙(9，10-PAH)，以其作为具有潜在抗癌活性的蒽环类配体，进一步分别合成了铜配合物[Cu(L1) Cl2]Cl (1)和{[Cu4(μ2-Cl)3Cl4(9，10-PAH)2(DMSO)2]Cl2}n (2)，其中新配体L1是2个9-PAH配体在配位反应中发生偶联形成。通过红外光谱、质谱及单晶衍射分析等手段表征了配合物的化学结构和晶体结构。晶体结构表明：配合物1为单核结构，L1通过其3个N原子与Cu配位，进而与2个Cl原子构成五配位的四方锥几何构型。配合物2则为聚合物结构，每个结构单元中包含2个呈中心对称的9，10-PAH-双核铜配合物，4个铜原子均采用五配位的四角锥几何构型。其中，每个9，10-PAH配体通过其吡啶腙双侧链与2个铜离子(Cu1、Cu2)分别形成五配位的双核结构，且Cu1与位于对称中心的1个桥联氯原子(Cl2)配位，Cl2同时与Cu1A配位，从而桥联这2个双核铜结构；而居于两侧的2个五配位的Cu2则分别通过1个配位的氯原子对称桥联相邻结构单元的Cu2A，进而构成一维链状聚合物结构。体外抗癌活性测试结果表明，2个配合物均表现出高于顺铂的较强细胞毒性，其中配合物2对2种癌细胞株HeLa-229和SK-OV-3的IC50值达到(5.92±0.32)μmol·L-1和(6.48±0.39)μmol·L-1。配合物2可将HeLa-229细胞增殖阻滞于S期，并显著诱导其凋亡。荧光猝灭竞争实验表明，配合物2可能以插入方式与DNA结合，与其抗癌机制密切相关。 | |
| 关键词: 蒽腙 金属配合物 晶体结构 抗癌活性 细胞凋亡 | |
| 基金项目: 国家自然科学基金(No.22167005)、云南开放大学高层次人才科研启动经费(No.060123070)、云财教 2024 年“三区”科技人才项目(No.061024023)和云南省一流学科“高原农业资源与环境”建设经费(No.060123076)资助。 | |
| Abstract: To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects, the new anthraquinone derivatives, 9 - pyridylanthrahydrazone (9 -PAH) and 9, 10 - bispyridylanthrahydrazone (9,10-PAH) were designed and synthesized. Utilizing 9-PAH and 9,10-PAH as promising anticancer ligands, their respective copper complexes, namely [Cu(L1) Cl2]Cl (1) and {[Cu4(μ2-Cl)3Cl4(9，10-PAH)2(DMSO)2]Cl2}n (2), were subsequently synthesized, where the new ligand L1 is formed by coupling two 9 - PAH ligands in the coordination reaction. The chemical and crystal structures of 1 and 2 were elucidated by IR, MS, elemental analysis, and single-crystal X-ray diffraction. Complex 1 forms a mononuclear structure. L1 coordinates with Cu through its three N atoms, together with two Cl atoms, to form a five-coordinated square pyramidal geometry. Complex 2 constitutes a polymeric structure, wherein each structural unit centrosymmetrically encompasses two five-coordinated binuclear copper complexes (Cu1, Cu2) of 9,10-PAH, with similar square pyramidal geometry. A chlorine atom (Cl2), located at the symmetry center, bridges Cu1 and Cu1A to connect the two binuclear copper structures. Meanwhile, the two five- coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom, respectively, thus forming a 1D chain-like polymeric structure. In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin. Specifically, the IC50 values of 2 against HeLa- 229 and SK-OV- 3 cancer cell lines were determined to be (5.92±0.32) μmol·L-1 and (6.48±0.39) μmol·L-1, respectively. 2 could also block the proliferation of HeLa-229 cells in S phase and significantly induce cell apoptosis. In addition, fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode, offering insights into its underlying anticancer mechanism. | |
| Keywords: anthrahydrazone metal complex crystal structure anticancer activity cell apoptosis | |
| 投稿时间：2024-10-08 修订日期：2024-12-25 | |
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| 黄遥,伍颖舒,包志春,黄悦,唐上峰,刘瑞雪,刘延成,梁宏.含吡啶侧链蒽腙-铜配合物的合成、晶体结构、抗肿瘤活性及DNA键合[J].无机化学学报,2025,41(1):213-224. | |
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