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 × 10⁵, 1.67 × 10⁵, 1.87 × 10⁵, and 1.007 × 10⁶ 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.

Graphical Abstract

Keywords:

• Oxopyrrolidine
• DNA binding
• Solution stability
• Hemolysis assays
• In silico studies
• Anticancer profiles

Acknowledgements

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this work. One of the authors (Waseem Ahmad Wani) is thankful to the University Grants Commission (UGC), New Delhi, for providing UGC-BSR research fellowship.