In vitro anti‐proliferative and in silico docking studies of heteroleptic copper(II) complexes of pyridazine‐based ligands and ciprofloxacin

Abstract

Three heteroleptic copper(II) complexes of the type [Cu(L1–3)(cf)(ClO4)] (1–3), where cf = ciprofloxacin, have been synthesized using pyridazine‐based ligands 3‐chloro‐6‐(salicylidenehydrazinyl)pyridazine (HL1), 3‐chloro‐6‐(4‐diethylaminosalicylidenehydrazinyl)pyridazine (HL2) and 3‐chloro‐6‐(5‐bromosalicylidenehydrazinyl)pyridazine (HL3). Electronic spectral data and magnetic moment values suggest octahedral geometry for the synthesized copper(II) complexes. Electrochemical data of the copper(II) complexes present an irreversible one‐electron reduction wave in the cathodic potential region (Epc) between −0.631 and −0.670 V. Frontier molecular orbital calculations were carried out, and the obtained low‐energy gap supports the bio‐efficacy of the complexes. All the complexes were screened for their in vitro cytotoxicity activity against three human cancerous (breast adenocarcinoma (MCF‐7), hepatoma (HepG‐2) and cervical (HeLa)) and one non‐cancerous (non‐tumorigenic human dermal fibroblast (NHDF)) cell lines using MTT assay, in which complex 2 exhibited higher activity. The apoptosis induction by the complexes was analysed using the Hoechst dye staining method with MCF‐7 cell line, which indicates higher apoptotic activity of complex 2. A molecular docking study was carried out to ascertain the binding affinity of the synthesized heteroleptic copper(II) complexes with phosphoinositide 3‐kinase gamma (PI3Kγ) receptor.

Metal complexes of tetradentate azo‐dye ligand derived from 4,4′‐oxydianiline: Preparation, structural investigation, biological evaluation and MOE studies

“…Two bands in the range 519-520 and 410-460 cm −1 were assigned to ν(M-O) and ν(M-N), respectively. [39,40] The IR spectra of the ligand and its metal complexes are shown in Figure S1. Finally, it is concluded from the IR spectra of all prepared compounds that the azo-dye ligand coordinated to the metal ions through four sites-two nitrogen sites of the azo groups and two oxygen sites by deprotonation of the phenolic groups.…”

Potential of Copper and Copper Compounds for Anticancer Applications

“…The inhibitory properties of copper(II) complexes on breast cancer cell proliferation were detected by MTT assay. The experiments showed that the complexes exhibited a significant proliferation inhibition effect on the human breast cancer cell line (MCF-7), and the cell viability was affected by the complexes [ 67 ]. The number of breast cancer cells decreased with increasing copper complex concentration.…”

Synthesis, structural characterization, density functional theory calculations, and antimicrobial, anticancer, and antimetastatic properties of nanosized heteroleptic complexes of cocaine/TMEDA with d‐block metal ions

“…In this context, heteroleptic transition metal complexes, which contain two or more different ligands, have gained particular attention as an important category of transition metal complexes [23][24][25][26][27][28] because of the stepwise dissociation during the formation of metal-DNA complexes, which enhances the cellular uptake and consequently the anticancer activity. [29,30] The azabicyclo[3.2.1]octane moiety composes the core structure of various biologically active compounds with antiproliferative, antimicrobial, analgesic, and antiinflammatory effects that are occasionally exploited as drugs.…”

“…In this context, heteroleptic transition metal complexes, which contain two or more different ligands, have gained particular attention as an important category of transition metal complexes [ 23–28 ] because of the stepwise dissociation during the formation of metal–DNA complexes, which enhances the cellular uptake and consequently the anticancer activity. [ 29,30 ]…”