Improving In Vivo Tumor Accumulation and Efficacy of Platinum Antitumor Agents by Electronic Tuning of the Kinetic Lability.

The impact of kinetic lability or reactivity on in vitro cytotoxicity, stability in plasma, in vivo tumor and tissue accumulation, and antitumor efficacy of functional platinum(II) (Pt) anticancer agents containing a O˄O β-diketonate leaving ligand remain largely unexplored. To investigate this, we synthesized Pt complexes [(NH ) Pt(L1-H)]NO and [(DACH)Pt(L1-H)]NO (L1=4,4,4-trifluoro-1-ferrocenylbutane-1,3-dione, DACH=1R,2R-cyclohexane-1,2-diamine) containing an electron deficient [L1-H] O˄O leaving ligand and [(NH ) Pt(L2-H)]NO and [(DACH)Pt(L2-H)]NO (L2=1-ferrocenylbutane-1,3-dione) containing an electron-rich [L2-H] O˄O leaving ligand. While all four complexes have comparable lipophilicity, the presence of the electron-withdrawing CF group was found to dramatically enhance the reactivity of these complexes toward nucleophilic biomolecules.

The Power of Kinetic Inertness in Improving Platinum Anticancer Therapy by Circumventing Resistance and Ameliorating Nephrotoxicity.

Even in the modern era of precision medicine and immunotherapy, chemotherapy with platinum (Pt) drugs remains among the most commonly prescribed medications against a variety of cancers. Unfortunately, the broad applicability of these blockbuster Pt drugs is severely limited by intrinsic and/or acquired resistance, and high systemic toxicity. Considering the strong interconnection between kinetic lability and undesired shortcomings of clinical Pt drugs, we rationally designed kinetically inert organometallic Pt based anticancer agents with a novel mechanism of action.

Platinum glycoconjugates: "Sweet bullets" for targeted cancer therapy?

Cancer, which is characterized by uncontrolled proliferation of abnormal cells, is a leading cause of morbidity and mortality worldwide. Cytotoxic chemotherapy, especially with platinum drugs, remains the mainstay of cancer treatment in the clinical setting. Despite phenomenal success, small-molecule chemotherapeutic drugs suffer from some serious drawbacks.

Challenges and opportunities in the development of metal-based anticancer theranostic agents.

Around 10 million fatalities were recorded worldwide in 2020 due to cancer and statistical projections estimate the number to increase by 60% in 2040. With such a substantial rise in the global cancer burden, the disease will continue to impose a huge socio-economic burden on society. Currently, the most widely used clinical treatment modality is cytotoxic chemotherapy using platinum drugs which is used to treat variety of cancers.

X-rays Actuate Anticancer Drugs: Opening New Vistas in Prodrug Therapy.

Chemotherapy is the primary treatment modality employed in the clinic for the treatment of cancer. Despite proven clinical success, adverse side effects are one of the drawbacks of this approach. The prodrug strategy has emerged as an alternative approach with the aim of alleviating these drawbacks.