Synthesis, crystal structure, DNA/protein interactions and cytotoxicity studies of tridentate ligand based Cu(II) complexes with various amine co-ligands

• Published in: Journal of molecular structure 2025-02, Vol.1321, p.139954, Article 139954
• Main Authors: Richa, Poonia, Gargi, Kiran, Thakur, Kanika, Dhiman, Nain Singh, Kumar, Ravinder, Kumar, Vijay, Sindhu, Jayant, Zangrando, Ennio, Kataria, Ramesh
• Format: Article
• Language: English
• Subjects: BSA, HSA, DNA fragmentation; Copper complexes; SKOV3
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.139954

•A set of eight complexes has been successfully synthesized by tailoring the methanol derivative [CuL(CH3OH)] (2) with chelating N-ligands.•This study examines the effects of different concentrations of Complex 7 on the absorption and fluorescence spectra of BSA/HSA.•Molecular dynamics studies reveal Complex 7′s enhanced binding affinity and stability with BSA/HSA.•SKOV3 cell lines were used to test the ligand and its complexes' anti-cancer effectiveness. The compound 7 showed superior anti-cancer activity, with an IC50 of 0.8 µM compared to doxorubicin.•Agarose gel electrophoresis showed that complex 7 induces DNA fragmentation. The present study utilizes a tridentate ligand H2L (1) derived as a condensation product of dehydroacetic acid and 2-furoic acid hydrazide for the synthesis of a series of copper complexes, namely [Cu(L)(bipy)] (3), [Cu(L)(4,4′-Me2-bipy)] (4), [Cu(L)(6,6′-Me2-bipy)] (5), [Cu(L)(phen)] (6), [Cu(L)(2,9-Me2-phen)] (7) [Cu(L)(pyrazino[2,3]phen)] (8) [Cu(L)(2,2′-dipyridylamine)] (9) [Cu(L)(diphenylmethanamine)] (10), obtained by reacting Cu(acetate)2 with the doubly deprotonated ligand and a range of co-ligand amines. All the synthesized compounds were fully structurally characterized using IR, 1H NMR, HRMS and single-crystal X-ray diffraction studies. The thermal stability and decomposition pattern was investigated using TGA studies. The bio-efficacy of the developed ligand and its complexes was evaluated in anti-cancer assay against SKOV3 cell lines. Copper complexes have been extensively studied for their potential to generate anticancer properties. Most complexes comprise mixed ligands, such as N-N-chelating heterocycles like 2,2’-bipyridine (bpy) and 1,10 phenanthroline (phen), chosen for their chelating and intercalative characteristics. Complex 7 displayed the highest anti-cancer activity with an IC50 value of 0.8 µM compared to standard drug doxorubicin. The impact of complex 7 on DNA fragmentation was also assessed through agarose gel electrophoresis, which indicated that complex 7 promotes observable DNA fragmentation. The serum binding affinity of the complex 7 was also investigated against BSA and HSA protein. The strong binding affinity of complex [Cu(L)(2,9-Me2-phen)] (7) with BSA/HSA and its better stability compared to the other investigated complexes were deduced based on its biological activity. The impact of varying concentrations of complex 7 on BSA and HSA was investigated using absorption spectroscopy, revealing t