Structural characterization and anticancer studies of copper(II) and cobalt(III) complexes containing N,O-donor heterocyclic chelators

Abstract

New Cu(II) and Co(III) complexes were synthesized from reaction of 3-((E)-1-(((E)-4-(diethylamino)-2-hydroxybenzylidene)hydrazono)ethyl)-8-methoxy-2H-chromen-2-one (HL) with Cu(NO₃)₂·3H₂O and Co(NO₃)₂·6H₂O in methanol. The synthesized compounds were characterized by various analytical and spectral (IR, UV-Vis, NMR, EPR, ESI-MS and HR-MS) techniques. From the spectral studies, we concluded that the formation of the ligand and complexes. In the copper complex with formula of [Cu₂(L)(NO₃)₃(H₂O)], HL coordinated to copper ion via azomethine nitrogen, lactone oxygen, azomethine nitrogen and oxalate oxygen atoms. In cobalt complex, the ligand coordinated to cobalt ion via ring carbonyl oxygen, azomethine nitrogen, oxalate oxygen and azomethine nitrogen, and the complex is of ML₂ type with the general formula [CoL₂]·2NO₃. The cytotoxic nature of the compounds was analyzed with human liver cancer cells (HepG2) and human breast cancer cells (MM2), in which the complexes exhibited a comparable activity than the positive control cisplatin. The IC₅₀ values of the compounds were greater than 200 μM for non-cancerous human umbilical vein endothelial (HUVEC) cells, indicating selectivity of the compounds towards cancer cells rather than normal cells. The apoptogenic natures of the complexes with HepG2 and MM2 cancer cells were confirmed using AO-EB and DAPI staining assays. These results revealed the possibility of developing highly active cobalt and copper complexes as anticancer agents.

Graphical Abstract

Keywords:

• Bivalent and trivalent metal complexes
• spectral characterization
• anticancer activity
• staining assays
• cancer cells

Acknowledgements

The authors (G.K., C.L. and L.S.) greatly acknowledges Karpagam Academy of Higher Education Management for providing research support. The author Dr. S.P. gratefully acknowledges Department of Science and Technology, India, for providing the Women Scientist Scheme – WOS (A) Fellowship, Department of Science and Technology, New Delhi, India [Grant No. SR/WOS(A)/CS-147/2021].

Conflicts of interest

The authors declare no competing financial interest.

Disclosure statement

No potential conflict of interest was reported by the authors.