Breast cancer is the most common malignant neoplasm among women and exhibits high molecular heterogeneity, which directly influences therapeutic response and clinical outcomes. Despite advances in targeted therapies and immunotherapies, tumor recurrence, resistance to conventional treatments, and metastatic potential reinforce the need for more selective and effective pharmacological strategies. In this context, metal complexes, particularly ruthenium(II) derivatives, have attracted considerable attention due to their antitumor profile, greater selectivity, and lower systemic toxicity. Therefore, in the present study, the antineoplastic activity of the RuMTZ complex (2-mercaptothiazoline-di-1,2-bis(diphenylphosphine)ethane-ruthenium(II)) was evaluated in three breast cancer cell lines (MDA-MB-231, MDA-MB-468 and MCF7) and in one non-tumor breast cell line (MCF10A). RuMTZ exhibited greater cytotoxicity against human MDA-MB-468 cells, as demonstrated by cell viability (IC50 = 1.8 µM) and clonogenic (IC50 = 0.08 µM) assays, associated with higher selectivity indexes (3.89 and 3.75, respectively). Further studies demonstrated that RuMTZ inhibited cell migration by up to 62.76
The study evaluated the current patterns of guideline-recommended clinical use, real-world utilization trends, and translational development of platinum-based (Pt-based) drugs through a comparative analysis of national and international pharmacotherapeutic guidelines, national drug utilization data, clinical trials, and emerging research directions. Cisplatin, carboplatin and oxaliplatin continue to play central roles across multiple malignancies and remain widely incorporated into recommended treatment protocols. Across all five guideline sources evaluated, Pt-based therapies were recommended in more than half of the 18 ICD-O topographic categories, with guideline coverage ranging from 55.6% to 83.3%. Real-world utilization data, using Bulgaria as a case study, indicated sustained and increasing use of Pt-based therapies between 2021 and 2024, with oxaliplatin showing the greatest increase. Current clinical trials focus primarily on optimizing established Pt-based regimens through combinations with immunotherapeutics and emerging drug candidates within increasingly personalized multimodal treatment strategies. In parallel, research efforts are directed toward the development of new Pt complexes, exploring next-generation approaches such as multifunctional Pt(IV) prodrugs and Pt-N-heterocyclic carbene compounds, as well as advanced drug-delivery systems, reflecting continued innovation in the field. Overall, Pt-based drugs remain essential in cancer therapy and continue to represent a dynamic area of research in biological inorganic chemistry and translational oncology.
Proton transfer is essential in all multi-electron transformations. Identifying the proton donor in such processes is crucial to understanding the catalytic mechanism and optimizing activity through pKa matching, which can enhance proton transfer rates. However, aqueous solutions offer multiple proton sources, which confounds clear identification of the catalytically relevant proton donor. In this work, we utilize a model hydrogenase, nickel-substituted rubredoxin (NiRd), which is capable of electrocatalytic hydrogen evolution. Prior mechanistic studies suggested a proton transfer process was involved in the rate determining step on the basis of isotopic substitution and kinetic modeling. In this study, the identity of the proton donor in this rate-determining step was investigated by employing a range of buffers with varied pKa values. The impacts of concentration and pH on catalytic currents and turnover frequencies (TOF) were investigated. These results suggest that intermolecular, buffer-dependent proton transfer is not the rate-determining step for catalysis under typical electrocatalytic conditions. Quantitative electrochemical simulations incorporating buffer information allowed extraction of intrinsic thermodynamic and kinetic parameters for catalysis. Ultimately, mechanistic distinctions between the NiRd system and other hydrogen-evolving catalysts suggest that controlling the proton donor may serve as a handle for modulating activity in an intentional manner.
Certain Clostridium pasteurianum strains encode up to four FeFe-hydrogenases, which are homologous (identity > 20
O2-tolerance is a desirable property for [FeFe] hydrogenases, which are highly efficient H2-producing catalysts. While most such enzymes are highly sensitive to aerobic environments, a small number of explored representatives exhibit exceptional stability and even H2-producing activity under oxygenic conditions. However, the genetic signatures of the O2-tolerance in this class of enzymes remain largely unknown. To address this knowledge gap, we explored a close homologue of a well-characterized O2-tolerant [FeFe] hydrogenase from Clostridium beijerinckii (CbHydA1)—a hydrogenase from Terrisporobacter glycolicus (TgHydA1). Our investigation indeed confirms that TgHydA1 can transition to the O2-stable Hinact state, a hallmark of O2 tolerance. The surprising outcome is that despite the high amino acid similarity, TgHydA1 shows a substantially higher propensity to remain in the Hinact state than CbHydA1. Using protein film electrochemical experiments, we demonstrate that the root of this behavior lies in roughly tenfold slower reactivation rates than those of CbHydA1 at any applied potential. This degree and direction of variation in reactivation kinetics have not been observed before for any other O2-tolerant [FeFe] hydrogenases or their variants to date, uncovering a yet-to-be-explored facet of reactivity alteration available to these enzymes. Overall, the results presented here highlight the importance of a holistic analysis of [FeFe] hydrogenase sequences in the context of their interaction with O2 that encompasses the protein environment and properties of the auxiliary metallocofactors.
