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. 2022 Sep 29:10:1028957.
doi: 10.3389/fchem.2022.1028957. eCollection 2022.

Cytotoxic mixed-ligand complexes of Cu(II): A combined experimental and computational study

Mamaru Bitew Alem  1 , Tadewos Damena  1 , Tegene Desalegn  1 , Moses Koobotse  2 , Rajalakshmanan Eswaramoorthy  3 , Kennedy J Ngwira  4 , Japheth O Ombito  5 , Matshediso Zachariah  2 , Taye B Demissie  5
Affiliations

Cytotoxic mixed-ligand complexes of Cu(II): A combined experimental and computational study

Mamaru Bitew Alem et al. Front Chem. .

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 IC50 of 4.29 µM, and the [Cu(II) (ciprofloxacin) (1,10-phenanthroline)] complex (2), with IC50 of 7.58 µM, were found to be more effective than the referenced drug, cisplatin which has IC50 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.

Keywords: BOILED-egg; Cu(II) complexes; DFT; MCF-7; antibacterial activity; cytotoxicity; molecular docking.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

SCHEME 1
SCHEME 1
The synthesis procedure of the two Cu(II) complexes (1 and 2).
FIGURE 1
FIGURE 1
FTIR Spectra of the synthesized metal complexes 1 (top) and 2 (bottom).
FIGURE 2
FIGURE 2
TGA (blue) and DTA (red) curves for complexes 1 and 2.
FIGURE 3
FIGURE 3
UV-Vis spectra of the synthesized mixed ligand metal complex 1.
FIGURE 4
FIGURE 4
UV-Vis spectra of 2 mixed ligand metal complexes.
FIGURE 5
FIGURE 5
HOMO—LUMO distribution and band gap energy of the synthesized metal complexes.
FIGURE 6
FIGURE 6
Mean inhibition zone diameter of mixed-drug metal complexes 1 and 2 and ciprofloxacin in mm at 25 and 50 µg/ml.
FIGURE 7
FIGURE 7
Cell viability of MCF-7 cancer cell line against complexes 1 and 2 and cisplatin.
FIGURE 8
FIGURE 8
BOILED egg model of the ligands (1,10-Phenanthroline, Ciprofloxacin, and metformin), 1, 2 and Cisplatin.
FIGURE 9
FIGURE 9
The (A) 3D and (B) 2D presentations of the binding interactions of complexes 1 and 2 against estrogen receptor alpha (ERα; PDB: 5GS4).
See this image and copyright information in PMC

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