Copper(II) Complexes with Tetradentate Piperazine-Based Ligands: DNA Cleavage and Cytotoxicity

Abstract

Five-coordinate Cu(II) complexes, [Cu(Ln)X]ClO4/PF6, where Ln = piperazine ligands bearing two pyridyl arms and X = ClO4− for Ln = L1 (1-ClO4), L2 (2-ClO4), L3 (3-ClO4), and L6 (6-ClO4) as well as [Cu(Ln)Cl]PF6 for Ln = L1 (1-Cl), L4 (4-Cl), and L5 (5-Cl) have been synthesized and characterized by spectroscopic techniques. The molecular structures of the last two complexes were determined by X-ray crystallography. In aqueous acetonitrile solutions, molar conductivity measurements and UV-VIS spectrophotometric titrations of the complexes revealed the hydrolysis of the complexes to [Cu(Ln)(H2O)]2+ species. The biological activity of the Cu(II) complexes with respect to DNA cleavage and cytotoxicity was investigated. At micromolar concentration within 2 h and pH 7.4, DNA cleavage rate decreased in the order: 1-Cl ≈ 1-ClO4 > 3-ClO4 ≥ 2-ClO4 with cleavage enhancements of up to 23 million. Complexes 4-Cl, 5-Cl, and 6-ClO4 were inactive. In order to elucidate the cleavage mechanism, the cleavage of bis(4-nitrophenyl)phosphate (BNPP) and reactive oxygen species (ROS) quenching studies were conducted. The mechanistic pathway of DNA cleavage depends on the ligand’s skeleton: while an oxidative pathway was preferable for 1-Cl/1-ClO4, DNA cleavage by 2-ClO4 and 3-ClO4 predominantly proceeds via a hydrolytic mechanism. Complexes 1-ClO4, 3-ClO4, and 5-Cl were found to be cytotoxic against A2780 cells (IC50 30–40 µM). In fibroblasts, the IC50 value was much higher for 3-ClO4 with no toxic effect.

Nuclease-like metalloscissors: Biomimetic candidates for cancer and bacterial and viral infections therapy

“…Accordingly, these actively ongoing techniques are categorized as follow: i) Preparation of multinuclear complexes wherein the metal cores cooperate to provides an efficient active binding site for biomolecules [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] . ii) Variation of the first coordination sphere towards synthesis of homoleptic and hetroleptic complexes [66] , [67] , [68] , [69] , [70] , [71] . iii) Modification of the second coordination sphere via addition of the functional groups or by using the supramolecular hosts such as cyclodextrins (CDs) [56] , [57] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] , [80] , [81] , [82] , [83] .…”

Synthesis, Characterization, DNA/HSA Interactions, and Anticancer Activity of Two Novel Copper(II) Complexes with 4-Chloro-3-Nitrobenzoic Acid Ligand

“…It has demonstrated anticancer activity and could be a formulant in innovative anticancer drugs [ 17 , 18 , 19 ]. Copper(II) complexes, such as hydroxytryptophan copper(II) [ 20 ], substituted derivatives of pregnenolone acetate copper(II) [ 21 ], thiosemicarbazone copper(II) [ 22 ], substituted carboxylic acid copper(II) [ 23 ], 1,10-phenanthroline derivative copper(II) [ 24 ], pyridine derivative copper(II) [ 25 ], thiosemicarbazone copper(II) [ 26 ], piperazine copper(II) [ 27 ], and schiff copper(II) [ 28 ], have been synthesized, and their anticancer efficacy has been assessed.…”

Synthesis and cytotoxicity against tumor cells of pincer N-heterocyclic ligands and their transition metal complexes

“…14,15 The pyrazole scaffold is a privileged pharmacophore encountered in many chemical compounds conrmed to be associated with various biological assets such as anti-inammatory, 16 antimicrobial and anticancer properties. 17,18 Furthermore, many compounds bearing a pyridine moiety have been identied to be biologically active [19][20][21][22] and therapeutically relevant in medicinal chemistry and to display versatile biological activities including antibacterial and anticancer activities. 18,23 In view of their biological signicant activity, the combination of pyrazole and pyridine moieties may lead to the synthesis of a new class of therapeutical active compounds, and is thus very much attractive.…”