DNA conformational changes and cleavage by ruthenium(II) nitrofurylsemicarbazone complexes

Metal complexes that establish interactions with DNA are being studied not only because of their potential use as therapeutic agents but also as tools for biochemistry and molecular biology. Searching for drugs with anti-trypanosome activity, we previously synthesized a series of ruthenium mixed ligand dimethyl sulfoxide complexes of the type Ru(II)Cl(2)(DMSO)(2)L], where L is 5-nitrofurylsemicarbazone derivatives and DMSO is dimethyl sulfoxide. Though they present the ability to bind DNA, no activity against parasites in cell culture was observed. Considering their potential application as molecular tools we further analyzed the interactions with DNA through an electrophoretic approach. Non covalent withdrawal of superhelicity and a rapid nicking activity upon covalent interaction was observed. Inhibition of both effects was observed in the presence of distamycin suggesting the involvement of the DNA minor groove in the interaction with the nitrofurylsemicarbazone ruthenium complexes. In addition cleavage inhibition by dimethyl sulfoxide suggests an oxidative mechanism of action.