Tetrazolo[1,5-a]pyrimidine-based metal(II) complexes as therapeutic agents: DNA interaction, targeting topoisomerase I and cyclin-dependent kinase studies

Abstract

A series of mononuclear nickel(II), copper(II) and zinc(II) complexes of the type [ML^1‒3Cl₂] (1–9) have been synthesized and characterized. All the complexes interact with CT–DNA through groove mode of binding and bring about prominent nuclease activity on plasmid DNA. The complexes strongly inhibit the topoisomerase I, and also strongly interact with cyclin-dependent kinase receptor. The cytotoxicity activity were assessed aganist three human cancer cell lines such as lung (A549), cervical (HeLa) and colon (HCT–15), in which the complex 5 shows highest activity against the colon (HCT-15) cancer cell. The apoptotic studies were also reported.

Keywords:

• Tetrazolo[1,5-a]pyrimidines
• DNA binding
• DNA cleavage
• Molecular docking
• Apoptosis

Acknowledgements

The authors are thankful to Sophisticated Analytical Instrument Facility (SAIF), Indian Institute Technology Madras (IIT-M), Chennai-600 036 for recording mass and EPR spectral analysis.