A Bis(dipyridophenazine)(2‐(2‐pyridyl)pyrimidine‐4‐carboxylic acid)ruthenium(II) Complex with Anticancer Action upon Photodeprotection

Abstract

Improving the selectivity of anticancer drugs towards cancer cells is one of the main goals of drug optimization; the prodrug strategy has been one of the most promising. A light-triggered prodrug strategy is presented as an efficient approach for controlling cytotoxicity of the substitutionally inert cytotoxic complex [Ru(dppz)2(CppH)](PF6)2(C1; CppH=2-(2-pyridyl)pyrimidine-4-carboxylic acid; dppz=dipyrido[3,2-a:2',3'-c]phenazine). Attachment of a photolabile 3-(4,5-dimethoxy-2-nitrophenyl)-2-butyl (DMNPB) ester ("photocaging") makes the otherwise active complex C1 innocuous to both cancerous (HeLa and U2OS) and non-cancerous (MRC-5) cells. The cytotoxic action can be successfully unleashed in living cells upon light illumination (350 nm), reaching similar level of activity as the parent cytotoxic compound C1. This is the first substitutionally inert cytotoxic metal complex to be used as a light-triggered prodrug candidate.

Re(I) carbonyl complexes: Multimodal platforms for inorganic chemical biology

“…In cells, they took advantage of the IR modality of the probe to quantify the internalization of the conjugates. They could also show that apparent discrepancies with fluorescence quantification were due to a variable fluorescence enhancement of the probes in membrane environment, which hampered rigorous quantification [13,[103][104][105][106]. In skin biopsies, the IR modality also enabled them to quantify the penetration of the peptide conjugate into skin, while the fluorescence modality could be used to compare its localization with those of nuclei, using common fluorescence stain like DAPI.…”

Evaluation of Perylene Bisimide‐Based RuII and IrIII Complexes as Photosensitizers for Photodynamic Therapy

“…[13][14][15] In the last years, our groups focused attention in the development of new Ru II -based PSs for PDT, antibacterial PDT (aPDT) and photoactivated chemotherapy (PACT). [16][17][18][19][20][21][22][23][24][25][26] Besides ruthenium, [27][28][29][30][31][32] other metals, such as iridium(III), rhenium(I), [33][34][35][36][37][38] Fe III , [39] Co III , [40] and Gd III [41] have been investigated by us and other groups in regard to traditional chemotherapy and PDT applications. [42][43][44][45] Compared with the Ru complexes, less effective PDT agents based on Ir compounds have been reported so far, probably because of the difficulties in suppressing the competing electron-transfer processes.…”

Lightening up Ruthenium Complexes to Fight Cancer?

“…We therefore decided to derivatize the carboxylic acid function with a photolabile functional group, namely 3-(4,5-dimethoxy-2-nitrophenyl)-2-butyl to allow for the control of the toxicity of 5. [25] Hence, we obtained the photoactivable complex 6 (Fig. 1), characterized by negligible or even absent toxicity in the dark on three different cell lines, namely MRC-5, HeLa and bone cancer U2OS cells, up to 48 h incubation (see Table 1-D).…”

“…[16][17][18][19] Over the past few years, our group, in collaboration with several colleagues, has investigated the use of metal complexes in the fields of PDT and PACT. [20][21][22][23][24][25][26][27][28] In particular, we focused our attention on Ru(ii) complexes. Ruthenium compounds are nowadays considered as the potential successors to Pt-based anticancer drugs.…”