The research groups of the network will collaborate by approaching the complex theme of the study of the interactions between inorganic systems and nucleic acids and their related pharmacological effects, especially their antitumour activity, by different complementary methods. The different themes that will be developed are platinum-based, ruthenium-based, other transition metal-based and tin-based antitumour drugs.The results one can expect from this type of investigation are: finding of new inorganic drugs and new insights in the structure-activity relationship; a better understanding of metal nucleic acid functionality and their role within the living systems; and a better knowledge of the relevance on metals in the living matter, together with their physiological and toxicological effects.
Research groups have collaborated in the study of the interactions between inorganic systems and nucleic acids and their related pharmacological effects, especially their antitumour activity, by different complementary methods. Results are as follows:
the interaction between platinum and palladium based antitumour drugs and nucleic acids has been studied, and structural investigations of binary peptide and ternary peptide nucleobase complexes of palladium(II) as well as of mixed platinum(II)-palladium(II) and platinum(II)-mercury(II) cytosine nucleobase compounds has been carried out;
the distortions induced in deoxyribonucleic acid (DNA) by cis or trans diamminedichloroplatinum (DDP) interstrand cross links have been characterized by deoxyribonuclease (DNase) I footprinting experiments;
the structures of the photoadducts formed between the guanosine-5'-monophosphate (GMP) and several ruthenium(II) complexes of polyazaaromatic ligands like Ru(TAP)32+ have been determined; it has been shown that the adduct is formed via covalent binding of a TAP ligand to the nitrogen 2 of guanine;
a series of diethylenetriamine pentaacetic acid (DTPA) bis amides and their lanthanum(III) complexes were prepared and characterized, as potential contrast agents for magnetic resonance imaging (MRI);
the substitution of hydrogen of fluorine, increasing the solubility of organotin compounds, has been shown to increase also their in vitro antitumour properties against human tumour cell lines.
Funding SchemeCSC - Cost-sharing contracts
WC1H 0PP London
2300 RA Leiden