Copper(II) complexes containing hydrazone and bipyridine/phenanthroline ligands for anticancer application against breast cancer cells

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Inorganic Biochemistry Pub Date : 2024-10-12 DOI:10.1016/j.jinorgbio.2024.112759

Dorothy Priyanka Dorairaj , Prashant Kumar , Haritha Rajasekaran , Nattamai Bhuvanesh , Sodio C.N. Hsu , Ramasamy Karvembu

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Abstract

In this work, mixed ligand Cu(II) complexes containing hydrazone and bipyridine ligands (CB1-CB5), or hydrazone and phenanthroline ligands (CP1-CP5) have been synthesized and characterized by spectroscopic and analytical techniques. Single crystal X-ray structure of complex CB1 revealed that two nitrogen atoms from bipyridine, one carbonyl oxygen, one azomethine nitrogen and one hydroxyl oxygen from the hydrazone ligand coordinated to Cu(II) ion, adopting a distorted square pyramidal geometry. Interaction of these complexes with calf thymus (CT) DNA and bovine serum albumin (BSA) was analyzed by absorption and emission studies. Further, the in vitro anticancer activity of the complexes was investigated exclusively against the breast cancer cells namely MCF7, T47D and MDA MB 231, and a normal breast MCF 10a cell line. The phenanthroline bearing complexes (CP1-CP5) displayed better activity than their bipyridine counterparts as seen from the IC₅₀ values. In addition, the most active complex CP1 having an IC₅₀ value of 5.8 ± 0.3 μM against T47D cancer cells was investigated for its mode of cell death through acridine orange/ethidium bromide(AO/EB), 4′,6-diamidino-2-phenylindole (DAPI) and Annexin-V fluorescein isothiocyanate (FITC) staining assays which revealed apoptosis. Lastly, the cell cycle analysis revealed that complex CP1 induced cell death in T47D cancer cells at the G0/G1 phase.

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含腙和联吡啶/菲罗啉配体的铜（II）配合物用于乳腺癌细胞的抗癌应用。

本研究合成了含有腙和联吡啶配体（CB1-CB5）或腙和菲罗啉配体（CP1-CP5）的混合配体铜（II）配合物，并利用光谱和分析技术对其进行了表征。络合物 CB1 的单晶 X 射线结构显示，双吡啶的两个氮原子、一个羰基氧、一个偶氮甲基氮以及腙配体的一个羟基氧与 Cu（II）离子配位，呈扭曲的正方形金字塔几何结构。通过吸收和发射研究分析了这些配合物与小牛胸腺（CT）DNA 和牛血清白蛋白（BSA）的相互作用。此外，还专门针对乳腺癌细胞 MCF7、T47D 和 MDA MB 231 以及正常乳腺细胞 MCF 10a 进行了体外抗癌活性研究。从 IC50 值可以看出，含菲罗啉的复合物（CP1-CP5）比双吡啶复合物具有更好的活性。此外，通过吖啶橙/溴化乙锭（AO/EB）、4',6-二脒基-2-苯基吲哚（DAPI）和附件素-V 异硫氰酸荧光素（FITC）染色检测，研究了对 T47D 癌细胞最具活性的复合物 CP1 的细胞凋亡模式，其 IC50 值为 5.8 ± 0.3 μM。最后，细胞周期分析表明，复合物 CP1 能诱导处于 G0/G1 期的 T47D 癌细胞死亡。

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来源期刊

Journal of Inorganic Biochemistry 生物-生化与分子生物学

CiteScore

7.00

自引率

10.30%

发文量

336

审稿时长

41 days

期刊介绍： The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.