Copper complexes of anthrahydrazone bearing pyridyl side chain:Synthesis,crystal structure,anticancer activity,and DNA binding  

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

作　　者：HUANG Yao WU Yingshu BAO Zhichun HUANG Yue TANG Shangfeng LIU Ruixue LIU Yancheng LIANG Hong 黄遥;伍颖舒;包志春;黄悦;唐上峰;刘瑞雪;刘延成;梁宏(云南开放大学化学化工学院,昆明650223;广西师范大学化学与药学学院,桂林541004)

机构地区：[1]School of Chemical Engineering,Yunnan Open University,Kunming 650223,China [2]School of Chemistry&Pharmaceutical Sciences,Guangxi Normal University,Guilin,Guangxi 541004,China

出　　处：《无机化学学报》2025年第1期213-224,共12页Chinese Journal of Inorganic Chemistry

基　　金：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);云南省一流学科“高原农业资源与环境”建设经费(No.060123076)资助。

摘　　要：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)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(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(Cl_(2)),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 IC_(50)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.CCDC:2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)Cl_(2)]Cl(1)和{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(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方锥几何构型。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(Cl_(2))配位,Cl_(2)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IC_(50)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：anthrahydrazone metal complex crystal structure anticancer activity cell apoptosis 

分 类 号：O614.121[理学—无机化学]