期刊
APPLIED ORGANOMETALLIC CHEMISTRY
卷 35, 期 4, 页码 -出版社
WILEY
DOI: 10.1002/aoc.6152
关键词
anticancer activity; DNA and HSA binding; FRET; MTT assay; tetranuclear and dinuclear copper(II) complexes
资金
- SERB [EMR/2017/001562]
A new dinuclear copper complex formed in solution and a tetranuclear compound in solid, exhibiting efficient DNA binding and anticancer activities. The complex showed strong binding affinity to human serum albumin and induced apoptosis in cancer cells.
The reaction of Cu(OAc)(2)center dot H2O with o-HOC6H4-C(H)(sic)N-NH-C((sic)S)-NH-N(sic)C(H)-C6H4OH-o in methanol resulted in the formation of a dinuclear Cu(II) complex [(o-phen)Cu(HL)Cu(HL)] (1) in the solution where HL2- is a new O-NN- ligand omicron-HOC6H4-C(H)=N-N=C-S-C(=N-NH)-C6H4OH-omicron formed in situ from cyclization of the Schiff base and the isolated product was found to be a dimer of 1 forming a tetranuclear compound in solid due to axial coordination of bridging phenolate O- as revealed from X-ray crystallography. Electronic spectroscopic study using calf thymus DNA as well as fluorescence quenching study of ethidium bromide bound DNA in presence of 1 showed intercalative DNA binding with K-b = 1.12 x 10(5) M-1 and K-app = 8.80 x 10(5) M-1, respectively. This compound was found to be efficient in hydrolytic as well as oxidative DNA cleavage. The binding interaction between complex 1 and human serum albumin (HSA) was investigated using fluorescence emission, absorption, and molecular docking studies. 3D fluorescence studies revealed that HSA structure was altered at secondary and tertiary levels. The binding constant K-a value (similar to 10(6) M-1) suggested a strong binding affinity of 1 to HSA, and the bimolecular quenching constant k(q) value (10(13) M-1 s(-1)) suggested a static quenching mechanism operative in the quenching of the intrinsic fluorescence of the protein. Such high k(q) value may also be accounted by Forster resonance energy transfer (FRET) process. The distance r (3.22 nm) between donor HSA and acceptor complex 1 calculated from FRET theory suggested that they are close to each other. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay with human cervical cancer HeLa cells and human breast cancer MCF7 cells (IC50 = 2.2 and 1.2 mu M, respectively) suggested remarkable in vitro anticancer activity of 1. Cell death in HeLa cells was induced via apoptosis as revealed from nuclear staining assays using Hoechst 33342 and acridine orange/propidium iodide dual staining, and apoptosis induction in HeLa cells happened through reactive oxygen species accumulation.
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