Differential cytotoxic and prooxidnant activity of knipholone and knipholone anthrone

Knipholone (KP) and knipholone anthrone (KA) are natural 4-phenylanthraquinone structural analogues with established differential biological effects including in vitro antioxidant [1] and antimicrobial properties [2]. The present study was designed to investigate the comparative in vitro cytotoxic activity and the possible mechanism of action of these two compounds. We demonstrated that KA is by order of magnitude more cytotoxic to mammalian cells than KP. In parallel with the demonstrated cytotoxic effect, KA but not KP induces prooxidative DNA damage in the presence of copper ions. In order to establish the possible involvement of reactive oxygen species in the KA-mediated prooxidative effect, we investigated the protective effect of several metal chelators and reactive oxygen species scavengers. Our data suggest that reactive oxygen species such as hydrogen peroxide are involved and a good correlation between prooxidative action, antioxidant effect and cytotoxicity is established for these two structural analogues. The chemistry, pharmacology and potential medicinal/toxicological potential of these compounds are discussed.

Synthesis of cycloruthenated compounds as potential anticancer agents

A library of 19 cycloruthenated derivatives is constructed by making use of the well-known cyclometalation reaction. Their geometries are modified in a straightforward manner by addition of either mono- or bidentate ligands, such as bipyridine, phenanthroline, 1,2-bis(diphenylphosphanyl)ethane, dimethylphenylphosphane, triphenylphosphane, and 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (PTA) ligands, to cationic cycloruthenated centers. The antitumor properties of the compounds thus obtained are investigated in order to compare them with recently reported ruthenium complexes and cisplatin. IC50 values against mammalian cells (A-172, HCT-116, and RDM-4) are determined for the library compounds and some of them, such as those derived from orthoruthenated phenylpyridine and a bidentate N,N ligand, display activity of the same order of magnitude as cisplatin.