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Anticancer evaluation of a manganese complex on HeLa and MCF-7 cancer cells: design, deterministic solvothermal synthesis approach, Hirshfeld analysis, DNA binding, intracellular reactive oxygen species production, electrochemical characterization and density functional theory

journal contribution
posted on 06.03.2020, 09:20 by Saghir Abbas, Faisal Rashid, Emine Ulker, Sumera Zaib, Khurshid Ayub, Sana Ullah, Muhammad Arif Nadeem, Sammer Yousuf, Ralf Ludwig, Saqib Ali, Jamshed Iqbal

Herein, a deterministic solvothermal strategy was employed to synthesize an efficient anticancer agent ‘cis-dichlorobis(1,10-phenanthroline)manganese(II)’ (Mn(phen)2Cl2). A single-crystal X-ray diffraction analysis revealed that Mn(phen)2Cl2 crystallizes in a triclinic system with the space group P-1. Cyclic voltammetric studies of Mn(phen)2Cl2 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)2Cl2 is quite stable and exists in sextet spin state (five unpaired electrons) as the most stable form and hence, Mn(phen)2Cl2 is a high spin complex. Mn(phen)2Cl2 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)2Cl2 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)2Cl2 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)2Cl2. Furthermore, an assessment of caspase-9 and caspase-3 activity after exposure to Mn(phen)2Cl2 in HeLa cells indicated that at IC50 values of Mn(phen)2Cl2, 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)2Cl2 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 ΔG = −14.62 kJ/mol.

Communicated by Ramaswamy H. Sarma

Funding

Saghir Abbas is grateful to the Higher Education Commission of Pakistan for the financial support to complete this work (PIN. NO. 112-31112-2-PS1-514) . Jamshed Iqbal is thankful to the Higher Education Commission of Pakistan for providing the financial support through Project No. Ph-V-MG-3/Peridot/R&D/HEC/2019.

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