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

Mamaru Bitew Alem; Tadewos Damena; Tegene Desalegn; Moses Koobotse; Rajalakshmanan Eswaramoorthy; Kennedy J Ngwira; Japheth O Ombito; Matshediso Zachariah; Taye B Demissie

doi:10.3389/fchem.2022.1028957

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

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

Authors

Mamaru Bitew Alem¹, Tadewos Damena¹, Tegene Desalegn¹, Moses Koobotse², Rajalakshmanan Eswaramoorthy³, Kennedy J Ngwira⁴, Japheth O Ombito⁵, Matshediso Zachariah², Taye B Demissie⁵

Affiliations

¹ Department of Applied Chemistry, Adama Science and Technology University, Adama, Ethiopia.
² School of Allied Health Professions, University of Botswana, Gaborone, Botswana.
³ Department of Biomaterials, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
⁴ Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Johannesburg, South Africa.
⁵ Department of Chemistry, University of Botswana, Gaborone, Botswana.

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.