Cytotoxic mixed-ligand complexes of Cu(II): A combined experimental and computational study
Mamaru Bitew Alem, Tadewos Damena, Tegene Desalegn, Moses O. Koobotse, Rajalakshmanan Eswaramoorthy, Kennedy J. Ngwira, Japheth O. Ombito, Matshediso Zachariah, Taye B. Demissie
Abstract
Herein, we report the synthesis of mixed-ligand Cu(II) complexes of metformin and ciprofloxacin drugs together with 1,10-phenanthroline as a co-ligand. The synthesized complexes were characterized using different spectroscopic and spectrometric techniques. In vitro cytotoxic activity against human breast adenocarcinoma cancer cell line (MCF-7) as well as antibacterial activity against two gram-negative and two gram-positive bacterial strains were also investigated. The analyses of the experimental results were supported using quantum chemical calculations and molecular docking studies against estrogen receptor alpha (ERα; PDB: 5GS4). The cytotoxicity of the [Cu(II) (metformin) (1,10-phenanthroline)] complex ( 1 ), with IC 50 of 4.29 µM, and the [Cu(II) (ciprofloxacin) (1,10-phenanthroline)] complex ( 2 ), with IC 50 of 7.58 µM, were found to be more effective than the referenced drug, cisplatin which has IC 50 of 18.62 µM against MCF-7 cell line. The molecular docking analysis is also in good agreement with the experimental results, with binding affinities of –7.35, –8.76 and –6.32 kcal/mol, respectively, for complexes 1 , 2 and cisplatin against ERα. Moreover, complex 2 showed significant antibacterial activity against E. coli (inhibition diameter zone, IDZ, = 17.3 mm), P. aeruginosa (IDZ = 17.08 mm), and S. pyogen (IDZ = 17.33 mm), at 25 μg/ml compared to ciprofloxacin (IDZ = 20.0, 20.3, and 21.3 mm), respectively. Our BOILED-egg model indicated that the synthesized metal complexes have potentially minimal neurotoxicity than that of cisplatin.