Ruthenium‐Containing Linear Helicates and Mesocates with Tuneable p53‐Selective Cytotoxicity in Colorectal Cancer Cells

Abstract

The ligands L and L both form separable dinuclear double-stranded helicate and mesocate complexes with Ru . In contrast to clinically approved platinates, the helicate isomer of [Ru (L ) ] was preferentially cytotoxic to isogenic cells (HCT116 p53 ), which lack the critical tumour suppressor gene. The mesocate isomer shows the reverse selectivity, with the achiral isomer being preferentially cytotoxic towards HCT116 p53 . Other structurally similar Ru -containing dinuclear complexes showed very little cytotoxic activity. This study demonstrates that alterations in ligand or isomer can have profound effects on cytotoxicity towards cancer cells of different p53 status and suggests that selectivity can be "tuned" to either genotype. In the search for compounds that can target difficult-to-treat tumours that lack the p53 tumour suppressor gene, [Ru (L ) ] is a promising compound for further development.

Preclinical Anticancer Activity of an Electron‐Deficient Organoruthenium(II) Complex

“…Furthermore, compound 1 is highly cytotoxic against the difficult‐to‐treat colorectal HCT116 p53 −/− cells. A current limitation in the treatment of colorectal cancer is the reduced cytotoxicity of clinically used chemotherapeutics towards cancer cells which lack the tumour suppressor p53 . Identifying molecules that are active towards both p53 wild‐type and p53 ‐null isogenic cancer cell clones of the human cancer cell line HCT116 is therefore of great interest …”

Mitochondrial‐DNA‐Targeted IrIII‐Containing Metallohelices with Tunable Photodynamic Therapy Efficacy in Cancer Cells

“…One the other hand, as promising mimics of protein α‐helices, metal‐directed self‐assembly of metallohelices (for example, helicates) with defined three‐dimensional stereochemical structures have shown structure‐inherent targeting abilities towards DNA . We thus proposed that a well‐designed Ir III ‐containing metallohelix that combines strong interactions with DNA targets and efficient 1 O 2 quantum yield may provide new motivation to achieve enhanced PDT for cancer treatment (Scheme ).…”

Mitochondrial‐DNA‐Targeted IrIII‐Containing Metallohelices with Tunable Photodynamic Therapy Efficacy in Cancer Cells

“…[12] One the other hand, as promising mimics of protein ahelices,m etal-directed self-assembly of metallohelices (for example,h elicates) with defined three-dimensional stereochemical structures have shown structure-inherent targeting abilities towards DNA. [13][14][15][16][17][18] We thus proposed that aw elldesigned Ir III -containing metallohelix that combines strong interactions with DNAt argets and efficient 1 O 2 quantum yield may provide new motivation to achieve enhanced PDT for cancer treatment (Scheme 1). However,t he construction of multinuclear Ir III -containing supramolecular architectures is still ac hallenge, [19] and the corresponding metallohelices have remained largely unexamined.…”