| Autor: |
Jana, Abhimanyu, Aher, Abhishek, Brandao, Paula, Bera, Pradip, Sharda, Saphy, Phadikar, Ujjwal, Manna, Sunil Kumar, Mahapatra, Ajit Kumar, Bera, Pulakesh |
| Předmět: |
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| Zdroj: |
Dalton Transactions: An International Journal of Inorganic Chemistry; 2/14/2022, Vol. 51 Issue 6, p2346-2363, 18p |
| Abstrakt: |
The reactions between 2-(pyridine-2-ylmethoxy)-benzaldehyde (L) and various primary amines furnish tridentate (L1 to L3) and tetradentate (L4) chelating ligands. The choice of different primary amines in the condensation reaction incorporates the chiral carbon atom in L2 and L3. A series of mononuclear cobalt(II) complexes, [CoII(L1)(Cl)2] (1), [CoII(L2)(Cl)2]·CH3CN (2), [CoII(L3)(Cl)2] (3), and [CoIII(L4)(N3)2] (4) are synthesized in the pure crystalline state from the resulting solution of cobalt(II) chloride and/or azide and respective ligand. The new ligands and cobalt complexes are characterized using spectral (UV-Vis, 1H-NMR, IR, and HRMS), cyclovoltammetric, and DFT studies. The structure of L1, L2, and all four cobalt complexes are determined by single X-ray crystallography. Cytotoxic activity of the compounds is evaluated using three different tissues of origin e.g., U-937 (histiocytic lymphoma), HEK293T (embryonic kidney), and A549 (lung carcinoma). The cobalt complexes are more active than the corresponding ligands against U-937 and HEK293T. The MTT assay demonstrates that the cobalt compounds are more effective anticancer agents against U-937 cancer cells than HEK293T and A549. The toxicity order, 1 (7.2 ± 0.3 μM) > 3 (11.4 ± 0.6 μM) > 2 (12 ± 0.1 μM) > 4 (29 ± 1 μM) is observed against U-937 cancer cells. All the compounds induce cell death through an apoptosis mechanism and all are ineffective against PBMCs. The mechanism of activity against U937 cancer cells involves caspase-3 activation and two different mitogen-activated protein kinases attesting the programmed cell death. Among the compounds, complexes 1, 2, and 3 show DNA cleavage activity both in oxidizing (H2O2) and reducing (GSH) environments. The mechanistic study reveals that singlet oxygen (1O2) is the major species involved in DNA cleavage. The absolute chemical hardness values of the ligands and 4 are relatively higher than 1, 2, and 3, which tacitly support the DNA cleavage experiment. The docking result indicates that the compounds under investigation strongly interact with DNA base pairs through a variety of interactions which attests successfully to the experimental results. A structure–activity relationship has been drawn to correlate the variation of antitumor activity with ligand conformations. [ABSTRACT FROM AUTHOR] |
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