Synthesis and Characterization of Juglone-Derived cu (II), Mn (II) and Zn (II) Complexes and Investigation of Their Cytotoxic Activities Against Lung and Colon Cancer Cells in Vitro and in Silico.

Three new Zn (II), Cu (II) and Mn (II) complexes have been synthesized from 5-hydroxy-1,4-naphthoquinone (HNQ). Elemental analysis, magnetic susceptibility, UV-Vis, IR and Mass spectrometry have all been used to explore the structural characterization of these compounds. When the electronic spectra of these compounds are examined, they correspond to π → π* transitions in the 261-262 nm range, n → π* transitions in the 316-354 nm range, and charge transfer transitions in the 417-423 nm range. Also, in vitro cytotoxic activities of both juglone ligand and its metal complexes against A549 lung cancer and HT-29 colon cancer cells have been investigated. The Mn (II)-Juglone complex showed better cytotoxic activity than juglone ligand and other metal complexes in both cell lines. Moreover, molecular docking analyses demonstrated that the Mn (II)-Juglone complex exhibited stronger binding interactions with both DNA and the anti-apoptotic protein Bcl-2 compared to the free Juglone ligand. Annexin V/PI double staining results using flow cytometry showed that there were more total apoptotic cells in the Mn (II)-Juglone complex-treated groups than in the ligand-treated groups in both cell lines. In addition, it was found that Cas-3 and Bax immunoreactivity increased significantly and Bcl-2 immunoreactivity decreased significantly in Mn (II)-Juglone complex-treated groups compared to the control and ligand groups.