The use of transition-metal complexes in oncology has enjoyed extensive attention given the tremendous success of platinum-based chemotherapeutics. Unfortunately, their efficacy in many cancers is limited by the development of resistance. We recently reported that ruthenium complexes, [(phen)2Ru(tatpp)]Cl2 (RPC3) and , [(phen)2Ru(tatpp)Ru(phen)2]Cl4 (RPC4) exhibit low acute animal toxicity, hypoxia potentiated cytotoxicity , and 83% tumor regression in non-small cell lung cancinoma (H358) human tumor xenografts. These RPCs cleave DNA under normoxic and hypoxic conditions, however the extent of DNA cleavage is inversely proportional to the pO2, suggesting enhanced activity against cells under hypoxic stress. In screening these RPCs against a number of normal and platinum resistant cell lines, we discovered that RPC4, in particular, showed good cytotoxicity against the platinum resistance lines. For example, the IC50’s for RPC3, RPC 4, and cisplatin in human cervical cancer cells (Hela) and platinum resistant Hela/CP are 15.1, 16.1, 7.0 and 34.0, 1.9, and 30.0 μM, respectively. RPC4 also showed an IC50 of 8.4 µM against platinum resistant human squalmous lung cancer (HCC2450). This paper will present our current understanding on the DNA cleavage mechanism and our findings on the cellular distribution. The normal vs malignant cytotoxicity and animal toxicity the these RPCs, and a number of closely related homoleptic and heteroleptic ruthenium(II) tris(diimines) will be compared and contrasted.

Development of redox-active ruthenium polypyridyl complexes as an anticancer agents for the treatment of platinum resistant tumors

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.