A Tridentate Cu(II) Complex with a 2-(4′-Aminophenyl)Benzothiazole Derivative: Crystal Structure and Biological Evaluation for Anticancer Activity
Barbara Mavroidi,
Marina Sagnou,
Eleftherios Halevas,
George Mitrikas,
Fotis Kapiris,
Penelope Bouziotis,
Antonios G. Hatzidimitriou,
Maria Pelecanou,
Constantinos Methenitis
Affiliations
Barbara Mavroidi
Inorganic Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Marina Sagnou
Institute of Biosciences & Applications, National Centre for Scientific Research “Demokritos”, 15310 Athens, Greece
Eleftherios Halevas
Institute of Biosciences & Applications, National Centre for Scientific Research “Demokritos”, 15310 Athens, Greece
George Mitrikas
Institute of Nanoscience and Nanotechnology, National Centre for Scientific Research “Demokritos”, 15310 Athens, Greece
Fotis Kapiris
Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research “Demokritos”, 15310 Athens, Greece
Penelope Bouziotis
Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research “Demokritos”, 15310 Athens, Greece
Antonios G. Hatzidimitriou
Inorganic Chemistry Laboratory, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Maria Pelecanou
Institute of Biosciences & Applications, National Centre for Scientific Research “Demokritos”, 15310 Athens, Greece
Constantinos Methenitis
Inorganic Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Herein, the synthesis, structural characterization and in vitro biological evaluation of a novel Cu(II) complex with the 2-(4-aminophenyl)benzothiazole pharmacophore conjugated with the (2-pyridinyl)methylamino chelating moiety is reported for the first time. A full characterization of the Cu(II) complex was conducted by X-ray crystallography, EPR, IR, elemental and MS analysis, and its binding to CT-DNA was investigated by UV-vis spectroscopy, ethidium bromide competition studies, circular dichroism, viscometry and thermal denaturation. The data clearly indicate that the Cu(II) complex interacts with CT-DNA via intercalation, registering a difference compared to previously reported Pt(II) and Pd(II) analogues. To evaluate the anticancer activity of the complex, a series of in vitro experiments against breast, glioblastoma, prostate and lung cancer cell lines along with healthy fibroblasts were implemented. Cytotoxicity, cellular uptake, intracellular ROS production, cell cycle and apoptosis analysis revealed an increased anticancer activity towards breast cancer cells that is accompanied by an induction in intracellular ROS levels and a significant G2/M arrest followed by apoptosis.
