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

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.

Cytotoxicity and Antibacterial Potentials of Mixed Ligand Cu(II) and Zn(II) Complexes: A Combined Experimental and Computational Study

“…The absorption peaks (experimental/TD-DFT) at 267/261 and 320/325 nm, due to π → π* transitions of the benzoyl system and the cinnamoyl system, respectively, were reported for chrysin. For 1,10-phenathroline free ligands (experimental/TD-DFT), the absorption peaks at 228/226 and 263/258 nm due to n → π* (CN) and π → π* (CC) transitions, respectively, were reported …”

“…The quantum chemical descriptors of the free ligands and the corresponding metal complexes are presented in Figure and Table S2, whereas the wave function distributions are shown in Figures and S3. In our previous study, we reported that the band gap energy ( E g ) has a strong correlation with various biological activities: antibacterial, antioxidant, and cytotoxicity. ,, Moreover, band gap energy has been used as an important stability descriptor. A compound with large band gap energy is suggested to be stable and hard, whereas that with small band gap energy is less stable, giving the compound softness and enhanced biological importance .…”

“…Ciprofloxacin (500 μM) in DMSO was used as a positive control, whereas DMSO was used as a negative control and no activity was found. The obtained results were presented in triplicates as a mean ± SD …”

“…The obtained results were presented in triplicates as a mean ± SD. 27 Antioxidant Activity Evaluation Using DPPH Radical Scavenging Activity. The capability of the synthesized metal complexes (1 and 2) as free radical scavengers was evaluated by conducting DPPH radicals and comparing the results with ascorbic acid as a standard antioxidant available.…”

Synthesis, characterization, and biological activities of zinc(II), copper(II) and nickel(II) complexes of an aminoquinoline derivative

“…In this regard, the syntheses of biologically active complexes have paramount significance. Research results over the past decades have witnessed that metal complexes were found to exhibit potential antimicrobial and antioxidant ( El-Gammal et al, 2021 ; Kargar et al, 2021 ; Kaya et al, 2021 ; Damena et al, 2022a ), antiviral ( Atasever Arslan et al, 2021 ), anticancer ( Malik et al, 2021 ), antidiabetic ( Koleša-Dobravc et al, 2018 ) and cytotoxicity ( Alem et al, 2022 ) activities. In this aspect, the ongoing search for natural products with potential biologically active ligands have confirmed that quinoline and its derivative ligands lie among the important classes of biologically active ligands.…”