Synthesis and characterization of mixed-ligand diimine-piperonal thiosemicarbazone complexes of ruthenium(II): Biophysical investigations and biological evaluation as anticancer and antibacterial agents

Authors

Floyd A. Beckford
Jeffrey Thessing
Michael Shaloski Jr.
P. Canisius Mbarushimana
Alyssa Brock
Jacob Didion
Jason Woods
Antonio Gonzalez-Sarrías, University of Rhode Island
Navindra P. Seeram, University of Rhode IslandFollow

Document Type

Article

Date of Original Version

2011

Department

Biomedical and Pharmaceutical Sciences

Abstract

We have used a novel microwave-assisted method developed in our laboratories to synthesize a series of ruthenium-thiosemicarbazone complexes. The new thiosemicarbazone ligands are derived from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) and the complexes are formulated as [(diimine)₂Ru(TSC)](PF₆)₂ (where the TSC is the bidentate thiosemicarbazone ligand). The diimine in the complexes is either 2,2′-bipyridine or 1,10-phenanthroline. The complexes have been characterized by spectroscopic means (NMR, IR and UV–Vis) as well as by elemental analysis. We have studied the biophysical characteristics of the complexes by investigating their anti-oxidant ability as well as their ability to disrupt the function of the human topoisomerase II enzyme. The complexes are moderately strong binders of DNA with binding constants of 10⁴ M⁻¹. They are also strong binders of human serum albumin having binding constants on the order of 10⁴ M⁻¹. The complexes show good in vitro anticancer activity against human colon cancer cells, Caco-2 and HCT-116 and indeed show some cytotoxic selectivity for cancer cells. The IC₅₀ values range from 7 to 159 μM (after 72 h drug incubation). They also have antibacterial activity against Gram-positive strains of pathogenic bacteria with IC₅₀ values as low as 10 μM; little activity was seen against Gram-negative strains. It has been established that all the compounds are catalytic inhibitors of human topoisomerase II.

Citation/Publisher Attribution

Beckford, F. A., Thessing, J., Shaloski Jr., M., Mbarushimana, P. C., Brock, A., Didion, J., Woods, J.,...Seeram, N. P. (2011). Synthesis and characterization of mixed-ligand diimine-piperonal thiosemicarbazone complexes of ruthenium(II): Biophysical investigations and biological evaluation as anticancer and antibacterial agents. Journal of Molecular Structure, 992(1-3), 39-47. doi: 10.1016/j.molstruc.2011.02.029

Available at: https://doi.org/10.1016/j.molstruc.2011.02.029

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