The ruthenium polypyridyl complexes [(phen)2Ru(tatpp)Ru(phen)2]4+ (Ru2P) and [(phen)2Ru(tatpp)]2+ (RuP) are promising anti-tumor agents that arrest H358 NSCLC tumor growth in mouse models, 4 and show cytotoxicity in the low µM range towards a number of platinum sensitive NSCLC lines (H358, H226, HOP62, H2087). Dose escalation toxicity studies in mice reveal that the compounds are safe at levels up to 67 mg drug/kg mouse and with no obvious side effects, when administered via ip injection.4 Mechanistic studies reveal that the key pharmacophore is the redox-active tatpp ligand which catalytically cleaves DNA via H-atom abstraction from the deoxyribose units. In an effort to determine how the metallation and metal oxidation state affect drug performance, we prepared a homometallic Re(I) tatpp dimer [Re2(CO)6(tatpp)(CH3CN)2](PF6)2 (Re2P) and a heterometallic dimer [(phen)2Ru(tatpp)Re(CO)3(CH3CN)](PF6)3 (RuReP) and examined their DNA cleavage activity as well as their anticancer potential. This paper will present the activity of Re2P and RuReP for DNA cleavage, cytotoxicity, and animal toxicity in comparison to parent drugs Ru2P and RuP.

Re(I) polypyridyl complexes in chemotherapy

249th National Meeting (2015)

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