Iridium(III) in-cell catalysis: a new strategy for the treatment of cancer

Abstract

Platinum-based chemotherapy is the most effective and widely used chemotherapy agent for the treatment of many different types of cancer. Unfortunately, the development of drug resistance has become a major obstacle to successful cancer treatment. Catalytic metallodrugs with anticancer properties, when administered at low concentrations, have the potential to mitigate adverse effects, offer innovative strategies to counteract resistance, and broaden the range of anticancer therapeutic efficacy. In this study, we use a stable chiral piano-stool organometallic iridium(III) complex, [Ir(arene)(TsDPEN)] (TsDPEN, N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine), to establish its in-cell catalyst property based on the Noyori-type asymmetric transfer hydrogenation process. Reduction of specific molecule is shown when the iridium(III) catalyst is co-administered with sodium formate as a source of hydride in both the model system and A2780 human ovarian cancer cells. The catalytic process exhibits preferential targeting of A2780 ovarian cancer cells over MRC5 non-cancerous fibroblasts. Moreover, to achieve a high potency to in-cell catalyst, we determined the antiproliferative activity (IC50) for sodium formate in A2780 cells, which guided the use of the limited concentration that can be used for sodium formate as a hydride source. The catalyst transfer hydrogenation strategy has the potential to both reduce cell proliferation and induce cell death, providing an effective therapy for cancer.