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

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 – 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.

Iron Chelators with Topoisomerase-Inhibitory Activity and Their Anticancer Applications

“…A similar correlation between top2a levels and the ability of other copper-complexed TSCs to inhibit cancer cell proliferation has been shown in mice-bearing cancer cells with either high or low levels of top2a (284). Ruthenium(II) metal complexed TSCs have also been shown to inhibit top2a (12). Thus, TSCs and other chelators complexed with iron or other divalent metal ions have shown activity against topoisomerases that is associated with anticancer cell killing.…”

Selective Enzymatic Transformation to Aldehydes in vivo by Fungal Carboxylate Reductase from Neurospora crassa

“…It can be found in some essential oils, vanilla and camphor,25, 26, 27 and has been shown to have antibacterial28 and anxiolytic effects 29. Moreover, some piperonal derivatives show a potential anticancer effect,30,31 antileishmanial activity,32 and other pharmacological effects 33…”

In VitroEffects of Novel Ruthenium Complexes in Neospora caninum and Toxoplasma gondii Tachyzoites

“…This has stimulated the interest in other compounds with more acceptable toxicity, such as ruthenium complexes (32)(33)(34)(35)(36). Effects of ruthenium compounds on some bacteria and parasites have been studied (37)(38)(39)(40)(41)(42)(43)(44)(45)(46). "Classical ruthenium complexes" contain heteroatom ligands (e.g., azole derivatives), and NAMI-A and KP-1019 have been evaluated in phase I clinical trials for cancer treatment (47)(48)(49).…”