Mono and dinuclear ruthenium (II) polypyridyl complexes (RPCs ) containing the redox-active 9,11,20,22-tetraazatetrapyrido [3,2-a:2',3'-c:3'',2''-l:2''',3''']pentacene (tatpp) ligand, are known to bind and damage DNA in vitro by a mechanism that is potentiated under low O2 conditions (hypoxia).  This paper will present the results of some structure-activity studies on the cytotoxicity, animal toxicity, and mouse tumor growth model for [Ru(phen)2(tatpp)]Cl2 (RPC1 ) and [(phen)2Ru(tatpp)Ru(phen)2]Cl4 (RPC2 ) and related RPCs. RPC1  and RPC2  were shown to be effective anticancer agents in-vitro as well as in-vivo in syngenic mouse B16 melanoma models and mice xenografted with human non small cell lung cancer (H358).  In vitro studies, reveal an unusual ligand-based free-radical mechanism of DNA cleavage which is correlated with the results of the structure-activity study.  The results suggest that RPC's with the tatpp ligand may be significantly more effective at targeting cancer cell under hypoxic stress.

Redox-active ruthenium(II) polypyridyl complexes (RPCs) as potential anti-cancer drugs with a hypoxia sensitizing mechanism

243rd National Meeting (2012)

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