One pot three component synthesis of DNA targeting phototoxic Ru(ii)-p-cymene dipyrido[3,2-a:2′,3′-c]phenazine analogues

Abstract

We have developed a one pot three component synthetic protocol for half-sandwich Ru(II)-p-cymene dipyrido[3,2-a:2′,3′-c]phenazine analogues for selective cancer therapy under light irradiation. On average, the cytotoxicity of all the complexes is indeed doubled upon light irradiation and also exhibited significant photo and dark selectivity against cancer cells with respect to normal cells. Out of five Ru(II) complexes (RuL1–RuL5), [(η⁶-p-cymene)Ru^IICl(K²-N,N-11-nitrodipyrido[3,2-a:2′,3′-c]phenazine]PF₆ (RuL4) exhibited the best phototoxicity (lowest IC₅₀ under light irradiation). Intracellular ROS generation was studied by the 2′,7′-dichlorofluorescein diacetate (DCFH-DA) assay. Moreover, these complexes exhibited a strong serum albumin and DNA binding capacity. These complexes also exhibited good stability in 10% DMSO-buffer and under 1 mM GSH conditions. Overall, the remarkable photocytotoxic efficacy of new Ru(II)-p-cymene dipyrido[3,2-a:2′,3′-c]phenazine analogues (RuL1–RuL5) makes them potential photochemotherapeutics as an alternative of current PDT agents.