Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics

Abstract

Countless expectations converge in the multidisciplinary endeavour for the search and development of effective and safe drugs in fighting cancer. Although they still embody a minority of the pharmacological agents currently in clinical use, metal-based complexes have great yet unexplored potential, which probably hides forthcoming anticancer drugs. Following the historical success of cisplatin and congeners, but also taking advantage of conventional chemotherapy limitations that emerged with applications in the clinic, the design and development of non-platinum metal-based chemotherapeutics, either as drugs or prodrugs, represents a rapidly evolving field wherein candidate compounds can be fine-tuned to access interactions with druggable biological targets. Moving in this direction, over the last few decades platinum family metals, e.g., ruthenium and palladium, have been largely proposed. Indeed, transition metals and molecular platforms where they originate are endowed with unique chemical and biological features based on, but not limited to, redox activity and coordination geometries, as well as ligand selection (including their inherent reactivity and bioactivity). Herein, current applications and progress in metal-based chemoth are reviewed. Converging on the recent literature, new attractive chemotherapeutics based on transition metals other than platinum—and their bioactivity and mechanisms of action—are examined and discussed. A special focus is committed to anticancer agents based on ruthenium, palladium, rhodium, and iridium, but also to gold derivatives, for which more experimental data are nowadays available. Next to platinum-based agents, ruthenium-based candidate drugs were the first to reach the stage of clinical evaluation in humans, opening new scenarios for the development of alternative chemotherapeutic options to treat cancer.

Antioxidant and Anticancer Potential of the New Cu(II) Complexes Bearing Imine-Phenolate Ligands with Pendant Amine N-Donor Groups

“…The cytotoxic activity of these metal complexes is attributed to interactions with cellular targets, such as binding to genomic DNA sequences and interaction with mitochondrial DNA and proteins [ 10 , 14 ]. However, these anticancer inorganics compounds have associated adverse effects that negatively impact the quality of life and inherent or acquired resistance [ 15 , 16 ]. Such limitations drive research in identifying novel anticancer metal complexes and therapeutic strategies to overcome the problem of chemoresistance and toxicity of the compounds currently in clinical use.…”

Influence of the Fatty Acid Metabolism on the Mode of Action of a Cisplatin(IV) Complex with Phenylbutyrate as Axial Ligands

“…Among them, the prodrug concept of platinum(IV) compounds has shown promising results. The higher oxidation state of the platinum center increases the compound’s kinetic inertness thereby reducing possible side effects in normal tissues [ 4 , 5 , 6 , 7 ]. Moreover, two additional (bioactive) axial ligands can be introduced, e.g., altering lipophilicity, pharmacokinetics, or generating multi-targeted complexes.…”

Investigating the Interaction of an Anticancer Nucleolipidic Ru(III) Complex with Human Serum Proteins: A Spectroscopic Study

“…Interest in Ru-based anticancer agents has rapidly increased since the discovery of their promising anticancer activity coupled with a significantly lower toxicity compared to known Pt-containing drugs [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].…”