Citation: Yao HUANG, Yingshu WU, Zhichun BAO, Yue HUANG, Shangfeng TANG, Ruixue LIU, Yancheng LIU, Hong LIANG. Copper complexes of anthrahydrazone bearing pyridyl side chain: Synthesis, crystal structure, anticancer activity, and DNA binding[J]. Chinese Journal of Inorganic Chemistry, ;2025, 41(1): 213-224. doi: 10.11862/CJIC.20240359 shu

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

Yao HUANG ^{1, 2, #} ,
Yingshu WU ^{2, #} ,
Zhichun BAO ² ,
Yue HUANG ² ,
Shangfeng TANG ² ,
Ruixue LIU ^2,, ,
Yancheng LIU ² ,
Hong LIANG ^2,,

1.
School of Chemical Engineering, Yunnan Open University, Kunming 650223, China
2.
School of Chemistry & Pharmaceutical Sciences, Guangxi Normal University, Guilin, Guangxi 541004, China

Corresponding author: Ruixue LIU, rxliu@gxnu.edu.cn Hong LIANG, hliang@gxnu.edu.cn
Received Date: 8 October 2024
Revised Date: 25 December 2024

Figures(5)

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.
- anthrahydrazone,
- metal complex,
- crystal structure,
- anticancer activity,
- cell apoptosis
1. [1]
  BRAY F, LAVERSANNE M, SUNG H, FERLAY J, SIEGEL R L, SOERJOMATARAM I, JEMAL A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA-Cancer J. Clin., 2024,74(3):229-263. doi: 10.3322/caac.21834
2. [2]
  TARTARONE A, GIORDANO P, LEROSE R, RODRIQUENZ M G, CONCA R, AIETA M. Progress and challenges in the treatment of small cell lung cancer[J]. Med. Oncol., 2017,34(6)110. doi: 10.1007/s12032-017-0966-6
3. [3]
  TAEFEHSHOKR N, BARADARAN B, BAGHBANZADEH A, TAEFEHSHOKR S. Promising approaches in cancer immunotherapy[J]. Immunobiology, 2020,225(2)151875. doi: 10.1016/j.imbio.2019.11.010
4. [4]
  SUN B, LUO C, CUI W, SUN J, HE Z. Chemotherapy agent-unsaturated fatty acid prodrugs and prodrug-nanoplatforms for cancer chemotherapy[J]. J. Control Release, 2017,264:145-159. doi: 10.1016/j.jconrel.2017.08.034
5. [5]
  PRATHIMA T S, CHOUDHURY B, AHMAD M G, CHANDA K, BALAMURALI M M. Recent developments on other platinum metal complexes as target-specific anticancer therapeutics[J]. Coord. Chem. Rev., 2023,490215231. doi: 10.1016/j.ccr.2023.215231
6. [6]
  WU Y P, LI S M, CHEN Y C, HE W J, GUO Z J. Recent advances in noble metal complex based photodynamic therapy[J]. Chem. Sci., 2022,13(18):5085-5106. doi: 10.1039/D1SC05478C
7. [7]
  FACCHETTI G, RIMOLDI I. Anticancer platinum(Ⅱ) complexes bearing N-heterocycle rings[J]. Bioorg. Med. Chem. Lett., 2019,29(11):1257-1263. doi: 10.1016/j.bmcl.2019.03.045
8. [8]
  MA L L, LI L W, ZHU G Y. Platinum-containing heterometallic complexes in cancer therapy: Advances and perspectives[J]. Inorg. Chem. Front., 2022,9(11):2424-2453. doi: 10.1039/D2QI00205A
9. [9]
  ŠTARHA P, TRÁVNíČEK Z. Non-platinum complexes containing releasable biologically active ligands[J]. Coord. Chem. Rev., 2019,395:130-145. doi: 10.1016/j.ccr.2019.06.001
10. [10]
  SHEN J C, REES T W, JI L N, CHAO H. Recent advances in ruthenium(Ⅱ) and iridium(Ⅲ) complexes containing nanosystems for cancer treatment and bioimaging[J]. Coord. Chem. Rev., 2021,443214016. doi: 10.1016/j.ccr.2021.214016
11. [11]
  WANG C H, YANG X D, DONG C Y, CHAI K, RUAN J, SHI S. Cu-related agents for cancer therapies[J]. Coord. Chem. Rev., 2023,487215156. doi: 10.1016/j.ccr.2023.215156
12. [12]
  VIMALRAJ S, RAJALAKSHMI S, RAJ PREETH D, VINOTH KUMAR S, DEEPAK T, GOPINATH V, MURUGAN K, CHATTERJEE S. Mixed-ligand copper(Ⅱ) complex of quercetin regulate osteogenesis and angiogenesis[J]. Mater. Sci. Eng. C ‒ Mater. Biol. Appl., 2018,83:187-194. doi: 10.1016/j.msec.2017.09.005
13. [13]
  YU T, SOLOSHONOK V A, XIAO Z K, LIU H, WANG J. Probing the dynamic thermodynamic resolution and biological activity of Cu(Ⅱ) and Pd(Ⅱ) complexes with Schiff base ligand derived from proline[J]. Chin. Chem. Lett., 2024,35(4)108901. doi: 10.1016/j.cclet.2023.108901
14. [14]
  HENRIKSEN P A. Anthracycline cardiotoxicity: An update on mechanisms, monitoring and prevention[J]. Heart, 2018,104(12):971-977. doi: 10.1136/heartjnl-2017-312103
15. [15]
  McGOWAN J V, CHUNG R, MAULIK A, PIOTROWSKA I, WALKER J M, YELLON D M. Anthracycline chemotherapy and cardiotoxicity[J]. Cardiovasc. Drugs Ther., 2017,31(1):63-75. doi: 10.1007/s10557-016-6711-0
16. [16]
  QU P R, JIANG Z L, SONG P P, LIU L C, XIANG M, WANG J. Saponins and their derivatives: Potential candidates to alleviate anthracycline-induced cardiotoxicity and multidrug resistance[J]. Pharmacol. Res., 2022,182106352. doi: 10.1016/j.phrs.2022.106352
17. [17]
  HULST M B, GROCHOLSKI T, NEEFJES J J C, VAN WEZEL G P, METSA-KETELA M. Anthracyclines: Biosynthesis, engineering and clinical applications[J]. Nat. Prod. Rep., 2022,39(4):814-841. doi: 10.1039/D1NP00059D
18. [18]
  GUO R F, YAN H T, LIU R X, LI H C, LIU Y C, CHEN Z F, LIANG H. Structural characterization and pharmacological assessment in vitro/in vivo of a new copper(Ⅱ)-based derivative of enrofloxacin[J]. Metallomics, 2020,12(12):2145-2160. doi: 10.1039/d0mt00155d
19. [19]
  LIU R X, WU Y S, LIU Y C, LUO R Y, YANG L D, TANG M T, CHEN Z F, LIANG H. New anthrahydrazone derivatives and their cisplatin-like complexes: Synthesis, antitumor activity and structure-activity relationship[J]. New J. Chem., 2019,43(47):18685-18694. doi: 10.1039/C9NJ02965F
20. [20]
  LIU R X, WANG C Y, WU Y S, LUO R Y, JIANG X H, TANG M T, LIU Y C, CHEN Z F, LIANG H. The copper(Ⅱ) complexes of new anthrahydrazone ligands: In vitro and in vivo antitumor activity and structure-activity relationship[J]. J. Inorg. Biochem., 2020,212111208. doi: 10.1016/j.jinorgbio.2020.111208
21. [21]
  LIU R X, LUO R Y, TANG M T, LIU Y C, CHEN Z F, LIANG H. The first copper(Ⅰ) complex of anthrahydrazone with potential ROS scavenging activity showed significant in vitro anticancer activity by inducing apoptosis and autophagy[J]. J. Inorg. Biochem., 2021,218111390. doi: 10.1016/j.jinorgbio.2021.111390
22. [22]
  BARTELS B, BOLAS C G, CUENI P, FANTASIA S, GAENG N, TRITA A S. Cu-catalyzed aerobic oxidative cyclization of guanidylpyridines and derivatives[J]. J. Org. Chem., 2015,80(2):1249-57. doi: 10.1021/jo502536t
23. [23]
  NAKKA M, TADIKONDA R, NAKKA S, VIDAVALUR S. Synthesis of 1, 2, 4-triazoles, N-Fused 1, 2, 4-triazoles and 1, 2, 4-oxadiazoles via molybdenum hexacarbonyl-mediated carbonylation of aryl iodides[J]. Adv. Synth. Catal., 2016,358(4):520-525. doi: 10.1002/adsc.201500703
24. [24]
  KOTSCHY A, FARAGÓ J, CSÁMPAI A, SMITH D M. The 'inverse electron-demand' Diels-Alder reaction in polymer synthesis. Part 5: Preparation and model reactions of some electron-rich bis-dienamines[J]. Tetrahedron, 2004,60(15):3421-3425. doi: 10.1016/j.tet.2004.02.035
1. [1]
  Jia JI , Zhaoyang GUO , Wenni LEI , Jiawei ZHENG , Haorong QIN , Jiahong YAN , Yinling HOU , Xiaoyan XIN , Wenmin WANG . Two dinuclear Gd(Ⅲ)-based complexes constructed by a multidentate diacylhydrazone ligand: Crystal structure, magnetocaloric effect, and biological activity. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 761-772. doi: 10.11862/CJIC.20240344
2. [2]
  Lu LIU , Huijie WANG , Haitong WANG , Ying LI . Crystal structure of a two-dimensional Cd(Ⅱ) complex and its fluorescence recognition of p-nitrophenol, tetracycline, 2, 6-dichloro-4-nitroaniline. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1180-1188. doi: 10.11862/CJIC.20230489
3. [3]
  Lulu DONG , Jie LIU , Hua YANG , Yupei FU , Hongli LIU , Xiaoli CHEN , Huali CUI , Lin LIU , Jijiang WANG . Synthesis, crystal structure, and fluorescence properties of Cd-based complex with pcu topology. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 809-820. doi: 10.11862/CJIC.20240171
4. [4]
  Xiaoling WANG , Hongwu ZHANG , Daofu LIU . Synthesis, structure, and magnetic property of a cobalt(Ⅱ) complex based on pyridyl-substituted imino nitroxide radical. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 407-412. doi: 10.11862/CJIC.20240214
5. [5]
  Xiaoxia WANG , Ya'nan GUO , Feng SU , Chun HAN , Long SUN . Synthesis, structure, and electrocatalytic oxygen reduction reaction properties of metal antimony-based chalcogenide clusters. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1201-1208. doi: 10.11862/CJIC.20230478
6. [6]
  Yinling HOU , Jia JI , Hong YU , Xiaoyun BIAN , Xiaofen GUAN , Jing QIU , Shuyi REN , Ming FANG . A rhombic Dy₄-based complex showing remarkable single-molecule magnet behavior. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 605-612. doi: 10.11862/CJIC.20240251
7. [7]
  Huan ZHANG , Jijiang WANG , Guang FAN , Long TANG , Erlin YUE , Chao BAI , Xiao WANG , Yuqi ZHANG . A highly stable cadmium(Ⅱ) metal-organic framework for detecting tetracycline and p-nitrophenol. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 646-654. doi: 10.11862/CJIC.20230291
8. [8]
  Ruikui YAN , Xiaoli CHEN , Miao CAI , Jing REN , Huali CUI , Hua YANG , Jijiang WANG . Design, synthesis, and fluorescence sensing performance of highly sensitive and multi-response lanthanide metal-organic frameworks. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 834-848. doi: 10.11862/CJIC.20230301
9. [9]
  Meirong HAN , Xiaoyang WEI , Sisi FENG , Yuting BAI . A zinc-based metal-organic framework for fluorescence detection of trace Cu²⁺. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1603-1614. doi: 10.11862/CJIC.20240150
10. [10]
  Xiumei LI , Yanju HUANG , Bo LIU , Yaru PAN . Syntheses, crystal structures, and quantum chemistry calculation of two Ni(Ⅱ) coordination polymers. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 2031-2039. doi: 10.11862/CJIC.20240109
11. [11]
  Xiumei LI , Linlin LI , Bo LIU , Yaru PAN . Syntheses, crystal structures, and characterizations of two cadmium(Ⅱ) coordination polymers. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 613-623. doi: 10.11862/CJIC.20240273
12. [12]
  Chao LIU , Jiang WU , Zhaolei JIN . Synthesis, crystal structures, and antibacterial activities of two zinc(Ⅱ) complexes bearing 5-phenyl-1H-pyrazole group. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1986-1994. doi: 10.11862/CJIC.20240153
13. [13]
  Yan XU , Suzhi LI , Yan LI , Lushun FENG , Wentao SUN , Xinxing LI . Structure variation of cadmium naphthalene-diphosphonates with the changing rigidity of N-donor auxiliary ligands. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 395-406. doi: 10.11862/CJIC.20240226
14. [14]
  Kaimin WANG , Xiong GU , Na DENG , Hongmei YU , Yanqin YE , Yulu MA . Synthesis, structure, fluorescence properties, and Hirshfeld surface analysis of three Zn(Ⅱ)/Cu(Ⅱ) complexes based on 5-(dimethylamino) isophthalic acid. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1397-1408. doi: 10.11862/CJIC.20240009
15. [15]
  Shuyan ZHAO . Field-induced Co^Ⅱ single-ion magnet with pentagonal bipyramidal configuration. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1583-1591. doi: 10.11862/CJIC.20240231
16. [16]
  Zhaodong WANG . In situ synthesis, crystal structure, and magnetic characterization of a trinuclear copper complex based on a multi-substituted imidazo[1,5-a]pyrazine scaffold. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 597-604. doi: 10.11862/CJIC.20240268
17. [17]
  Xiaowei TANG , Shiquan XIAO , Jingwen SUN , Yu ZHU , Xiaoting CHEN , Haiyan ZHANG . A zinc complex for the detection of anthrax biomarker. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1850-1860. doi: 10.11862/CJIC.20240173
18. [18]
  Peng Meng , Qian-Cheng Luo , Aidan Brock , Xiaodong Wang , Mahboobeh Shahbazi , Aaron Micallef , John McMurtrie , Dongchen Qi , Yan-Zhen Zheng , Jingsan Xu . Molar ratio induced crystal transformation from coordination complex to coordination polymers. Chinese Chemical Letters, 2024, 35(4): 108542-. doi: 10.1016/j.cclet.2023.108542
19. [19]
  Chao Ma , Cong Lin , Jian Li . MicroED as a powerful technique for the structure determination of complex porous materials. Chinese Journal of Structural Chemistry, 2024, 43(3): 100209-100209. doi: 10.1016/j.cjsc.2023.100209
20. [20]
  Xiaoling LUO , Pintian ZOU , Xiaoyan WANG , Zheng LIU , Xiangfei KONG , Qun TANG , Sheng WANG . Synthesis, crystal structures, and properties of lanthanide metal-organic frameworks based on 2, 5-dibromoterephthalic acid ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1143-1150. doi: 10.11862/CJIC.20230271

Get Citation

PDF

XML

Metrics

PDF Downloads(1)
Abstract views(259)
HTML views(28)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142