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

We have developed a one pot three component synthetic protocol for half-sandwich Ru(II)-p-cymene dipyrido[3,2-a:2',3'-clphenazine analogues for selective cancer therapy under Eight irradiation. On average, the cytotoxicity of all the complexes is indeed doubled upon Eight 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), [(eta(6)-p-cymene)(RuCE)-C-1(K-2-N,N-11-nitrodipyrido[3,2-a:2',3'-c]phenazine]PF6 (RuL4) exhibited the best phototoxicity (Lowest IC50 under Eight 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.

Automated summary

We have developed a synthetic protocol for selective cancer therapy using half-sandwich Ru(II)-p-cymene dipyrido[3,2-a:2',3'-clphenazine analogues. Under irradiation, the cytotoxicity of all complexes is doubled and they exhibit significant selectivity against cancer cells. One complex (RuL4) shows the best phototoxicity. These complexes also have strong binding capacity to serum albumin and DNA, and display good stability.