Aldrich-Wright Group; 

Keywords: anticancer, metallointercalators, biological activity, NMR, platinum

Within our group we have developed new types of metallodrugs, which bind to DNA by various mechanisms such as intercalation, groove binding and coordination. Our range of metallodrugs includes a soluble transplatin analogue with an attached cyclodextrin; groove binding, intercalating and sequence selective compounds, intercalating platinum complexes such as [Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)]Cl₂ (56MESS), homonuclear bisintercalating compounds complexes based on (2,2′:6′,2′′-terpyridine)platinum(II) or [(dpq)₂Ru(phen-n-SOS-n-phen)Ru(dpq)₂]₄+ and trinuclear heteronuclear covalent binding metal complexes. From this group, a lead drug has been identified, 56MESS, which has shown activity better than cisplatin in several cell lines. Each compound has been designed to bind to DNA by different mechanisms and we are assessing the effectiveness of these strategies by measuring the effects on cell proliferation and viability.