Induced apoptosis against U937 cancer cells by Fe(II), Co(III) and Ni(II) complexes with a pyrazine-thiazole ligand: synthesis, structure and biological evaluation
| Autor: | Gopinath Mondal, Abhimanyu Jana, Ananyakumari Santra, Harekrishna Jana, Sunil K. Manna, Abhishek Aher, Paula Brandão, Pradip Bera, Pulakesh Bera |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Pyrazine
010405 organic chemistry Chemistry Hydrogen bond Ligand Iron(II) complex Cytotoxicity chemistry.chemical_element Nickel(II) complex Triclinic crystal system 010402 general chemistry 01 natural sciences Redox 0104 chemical sciences Pyrazine thiazole Inorganic Chemistry chemistry.chemical_compound Crystallography Materials Chemistry Physical and Theoretical Chemistry DNA binding Thiazole Cobalt(III) complex Cobalt HOMO/LUMO |
| Popis: | Complexes of iron(II), cobalt(III) and nickel(II) with 4-(4-methoxyphenyl)-2-(2-(1-(pyrazin-2yl)ethylidene)hydrazinyl)thiazole (PyztH) have been synthesized and characterized by elemental analyses, spectroscopic methods, CV measurements and a DFT study. The crystal and molecular structures were determined by the X-ray diffraction method. The complexes have the compositions [Fe(Pyzt)2]Br2 (1), [Co(Pyzt)2]PF6 (2) and [Ni(Pyzt)(PyztH)]ClO4 (3), with an approximate octahedral environment around the metal centre with NNN donor atoms from the two coordinating ligands. The complexes belong to the triclinic crystal system and crystallize in the space group P-1. Complex 1 is stabilized by strong hydrogen bonds, whereas the stability of complexes 2 and 3 is associated to π–π stacking interactions. The chemical reactivity, frontier orbital picture and energies of the HOMO and LUMO of the complexes have been estimated by a DFT study. The complexes are redox active species and respond with a quasi-reversible redox process. The cytotoxicity of the complexes was tested against U-937 human monocytic cells and shows IC50 values of 132 (for 1), 45 (for 2) and 162 µM (for 3). A LDH release assay indicates that 2 and 3 show apoptosis in the tumour cell. Complex 2 induces apoptosis by disrupting the mitochondrial membrane potential and homeostasis leading to cytotoxicity, as envisaged by PARP cleavage. Complexes 1, 2 and 3 show high binding constants (2.01 × 106 M−1 for 1, 1.18 × 107 M−1 for 2 and 2.90 × 107 M−1 for 3) with CTDNA which attest the groove binding nature of the complexes with DNA. The compounds also exhibit a remarkable zone of inhibition against specific tested bacterial and fungal strains. Based on the results, the cobalt complex (2) shows the best antitumor and antimicrobial activity among the complexes under investigation. |
| Databáze: | OpenAIRE |
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