The first examples of Ru(II) h6-arene (benzene and p-cymene) complexes containing a bidentate triazolylidene-triazolide ligand have been prepared and fully characterized. Their antiproliferative effect has been investigated against tumour cells A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), and HCT116dox (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The Ru complex bearing the p-cymene arene group exhibited a stronger antiproliferative effect across all tested cell lines, while the benzene-containing complex displayed higher selectivity toward tumor cells. Both complexes induced apoptosis, likely through ROS production (in the benzene complex), and inhibited tumorigenic processes, including cell migration and angiogenesis. In zebrafish models, they showed strong selectivity for cancer cells with minimal toxicity to healthy cells, effectively reducing the proliferation of HCT116 colorectal cancer cells. This study provides the first in vivo evidence of the anticancer potential of Ru triazolylidenes in zebrafish models.

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising, and prognosis remains poor due to late diagnosis and limited effective therapies. Currently, patients are treated based on TNM staging, without molecular tumor characterization. This study aimed to validate a technique that combines the amplification refractory mutation system (ARMS) with high-resolution melting analysis (HRMA) for detecting mutations in codon 12 of KRAS in tumor and plasma, and to assess its prognostic value. Methods: Prospective study including patients with newly diagnosed PDAC with tumor and plasma samples collected before treatment. Mutations in codon 12 of KRAS (G12D, G12V, G12C, and G12R) were detected using ARMS–HRMA and compared to Sanger sequencing (SS). Univariate and multivariate analyses were used to evaluate the prognostic significance of these mutations. Results: A total of 88 patients, 93% with ECOG-PS 0–1, 57% with resectable disease. ARMS–HRMA technique showed a higher sensitivity than SS, both in tumor and plasma (77% vs. 51%; 25 vs. 0%, respectively). The most frequent mutation was G12D (n = 32, 36%), followed by G12V (n = 22, 25%). On multivariate analysis, patients with G12D and/or G12C mutations, either in tumor or plasma, had lower PFS (HR 1.792, 95% CI 1.061–3.02

Metal-dependent formate dehydrogenases reduce CO2 with high efficiency and selectivity, but are usually very oxygen sensitive. An exception is Desulfovibrio vulgaris W/Sec-FdhAB, which can be handled aerobically, but the basis for this oxygen tolerance was unknown. Here we show that FdhAB activity is controlled by a redox switch based on an allosteric disulfide bond. When this bond is closed, the enzyme is in an oxygen-tolerant resting state presenting almost no catalytic activity and very low formate affinity. Opening this bond triggers large conformational changes that propagate to the active site, resulting in high activity and high formate affinity, but also higher oxygen sensitivity. We present the structure of activated FdhAB and show that activity loss is associated with partial loss of the metal sulfido ligand. The redox switch mechanism is reversible in vivo and prevents enzyme reduction by physiological formate levels, conferring a fitness advantage during O2 exposure.