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

Abbas S., Rashid F., Ulker E., Zaib S., Ayub K., Ullah S., ...More

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, vol.39, no.3, pp.1068-1081, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 39 Issue: 3
  • Publication Date: 2021
  • Doi Number: 10.1080/07391102.2020.1726818
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.1068-1081
  • Keywords: Mn complex, Hirshfeld surface analysis, anticancer potential, DNA binding, electrochemistry, DFT studies, CYCLE ARREST, APOPTOSIS, CYTOTOXICITY, INHIBITION, RESISTANCE, CASPASE-9, TOXICITY, LINE, ROS
  • Recep Tayyip Erdoğan University Affiliated: Yes


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