期刊
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
卷 39, 期 3, 页码 1068-1081出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2020.1726818
关键词
Mn complex; Hirshfeld surface analysis; anticancer potential; DNA binding; electrochemistry; DFT studies
资金
- Higher Education Commission of Pakistan [112-31112-2PS1-514, Ph-V-MG-3/Peridot/RD/HEC/2019]
A deterministic solvothermal strategy was employed to synthesize an efficient anticancer agent Mn(phen)(2)Cl-2, which showed significant anticancer potential against specific cancer cells and low toxicity towards normal cells. Various experiments confirmed its anticancer mechanisms, including inducing oxidative stress and apoptosis in cancer cells.
Herein, a deterministic solvothermal strategy was employed to synthesize an efficient anticancer agent 'cis-dichlorobis(1,10-phenanthroline)manganese(II)' (Mn(phen)(2)Cl-2). A single-crystal X-ray diffraction analysis revealed that Mn(phen)(2)Cl-2 crystallizes in a triclinic system with the space group P-1. Cyclic voltammetric studies of Mn(phen)(2)Cl-2 indicated that the electrode process occurs only due to complex formation and has a diffusion-controlled mechanism. Density functional theory estimations showed that the Mn(phen)(2)Cl-2 is quite stable and exists in sextet spin state (five unpaired electrons) as the most stable form and hence, Mn(phen)(2)Cl-2 is a high spin complex. Mn(phen)(2)Cl-2 demonstrated significant anticancer potential against HeLa and MCF-7 cancer cells and less toxic behaviour towards normal BHK-21 cells. Fluorescence imaging confirmed that the production of reactive oxygen species (ROS) in HeLa cells by Mn(phen)(2)Cl-2 induces oxidized fluorescence of dichlorofluorescein which emitted fluorescence at 530 nm after excitation at 488 nm. The microscopic investigation of apoptotic effect of Mn(phen)(2)Cl-2 using propidium iodide and 4 ',6-diamidino-2-phenylindole staining indicated that nuclear condensation, cell detachment and shrinkage occur after treatment with IC50 values of Mn(phen)(2)Cl-2. Furthermore, an assessment of caspase-9 and caspase-3 activity after exposure to Mn(phen)(2)Cl-2 in HeLa cells indicated that at IC50 values of Mn(phen)(2)Cl-2, 1.5 fold and 4.8 fold increase in caspase-9 and caspase-3 activity, respectively, occurs. The measurement of mitochondrial membrane potential of a cationic dye (JC-1) showed a decrease in mitochondrial membrane potential in both HeLa and MCF-7 cells depicting that compound might have adopted intrinsic pathway of apoptosis. Ability of Mn(phen)(2)Cl-2 to interact with HS-DNA demonstrates hyperchromicity with slight blue shift from 269 nm to 265 nm showing a non-covalent interaction with Gibbs free energy of Delta G = -14.62 kJ/mol. Communicated by Ramaswamy H. Sarma
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