Copper(II), nickel(II), and ruthenium(III) complexes of an oxopyrrolidine-based heterocyclic ligand as anticancer agents

Abstract

An oxopyrrolidine-based ligand [3-(4-chlorobenzylidine)-5-(5-amino-1,3,4-thiadiazol-2-yl)pyrrolidin-2-one] was synthesized by coupling pyroglutamic acid with p-chlorobenzaldehyde followed by cyclization with thiosemicarbazide in presence of oxyphosphoryl chloride. Copper, nickel, and ruthenium complexes of the ligand were also synthesized. The electrolytic nature, with octahedral geometries for nickel and ruthenium complexes, was observed, while tetragonally distorted octahedral geometry for copper complex was proposed. The complexes were resistant to dissociation and degradation in 5% DMSO solutions of PBS (pH 7.4). DNA binding constants (K b ) for ligand, copper, nickel, and ruthenium complexes were 1.15 × 10 5 , 1.67 × 10 5 , 1.87 × 10 5 , and 1.007 × 10 6 M −1 , respectively, indicating quite strong binding with DNA. In silico studies also showed that the ligand interacted with DNA mainly through van der Waal's forces. The docking energy of ligand−DNA adduct was -30.45 kJ M -1 , suggesting a good affinity of the reported ligand with DNA. Both the ligand and its complexes were less toxic to RBCs as compared to doxorubicin. All the compounds showed moderate anticancer activities on MCF-7 (wild type) breast cancer cell lines.

Synthesis, structure, computational, antimicrobial andin vitroanticancer studies of copper(II) complexes with N,N,N′,N′-tetrakis(2-hydroxyethyl)ethylenediamine and tris(2-hydroxyethyl)amine

“…The IC 50 value of synthesized complexes compares well with those reported for cytotoxic copper(II) complexes giving IC 50 values in similar concentration range [11][12][13][14][15]. This study suggests that 1 and 2 have potential as anticancer agents.…”

“…Macrocyclic dicopper(II) complexes have shown cytotoxicity in human cervical HeLa cancer cells lines [14]. Recently, Wani et al have reported the moderate cytotoxic activity of a Cu(II) complex based on oxopyrrolidine-based heterocyclic ligand [15]. In the present paper, both Cu(II) complexes were assessed for their possible antimicrobial and cytotoxic properties.…”

Synthesis, Characterization, DNA Binding, Anticancer, and Molecular Docking Studies of Novel Imidazolium-Based Ionic Liquids with Fluorinated Phenylacetamide Tethers

“…DNA is among the most significant pharmaceutical targets of anticancer medications. − Thus, studying the interactions of target compounds with DNA is important to get an indication about their anticancer impacts and imaginable mechanisms of action. In general, a compound and DNA formed covalent and noncovalent bonds.…”

Schiff Bases: Multipurpose Pharmacophores with Extensive Biological Applications

“…Imine based Schiff bases like N-hydroxy-N‫-׳‬ aminoguanidine L 20 block ribo-nucleotide reductase in tumor cells, hence they are used in the treatment of leukemia [17]. Similarly Schiff bases based on cumarin and pyrazole aldehyde L 24 showed mild anti-cancerous capabilities [19]. Some mono and bis-Schiff bases are effective against five cancer cell lines [20].…”