Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey

Owing to the growing hardware capabilities and the enhancing efficacy of computational methodologies, computational chemistry approaches have constantly become more important in the development of novel anticancer metallodrugs. Besides traditional Pt-based drugs, inorganic and organometallic complexes of other transition metals are showing increasing potential in the treatment of cancer. Among them, Au(I)- and Au(III)-based compounds are promising candidates due to the strong affinity of Au(I) cations to cysteine and selenocysteine side chains of the protein residues and to Au(III) complexes being more labile and prone to the reduction to either Au(I) or Au(0) in the physiological milieu. A correct prediction of metal complexes’ properties and of their bonding interactions with potential ligands requires QM computations, usually at the ab initio or DFT level. However, MM, MD, and docking approaches can also give useful information on their binding site on large biomolecular targets, such as proteins or DNA, provided a careful parametrization of the metal force field is employed. In this review, we provide an overview of the recent computational studies of Au(I) and Au(III) antitumor compounds and of their interactions with biomolecular targets, such as sulfur- and selenium-containing enzymes, like glutathione reductases, glutathione peroxidase, glutathione-S-transferase, cysteine protease, thioredoxin reductase and poly (ADP-ribose) polymerase 1.

Cellular Basis of Organotin(IV) Derivatives as Anticancer Metallodrugs: A Review

Organotin(IV) compounds have wide applications in industrial and agricultural fields owing to their ability to act as poly(vinyl chloride) stabilizers and catalytic agents as well as their medicinal properties. Moreover, organotin(IV) compounds may have applications as antitumor, anti-inflammatory, antifungal, or antimicrobial agents based on the observation of synergistic effects following the binding of their respective ligands, resulting in the enhancement of their biological activities. In this review, we describe the antiproliferative activities of organotin(IV) compounds in various human cancer cell lines based on different types of ligands. We also discuss the molecular mechanisms through which organotin(IV) compounds induce cell death via apoptosis through the mitochondrial intrinsic pathway. Finally, we present the mechanisms of cell cycle arrest induced by organotin(IV) compounds. Our report provides a basis for studies of the antitumor activities of organotin(IV) compounds and highlights the potential applications of these compounds as anticancer metallodrugs with low toxicity and few side effects.

Fluorinated-NHC Transition Metal Complexes Leading Characters as Potential Anticancer Metallodrugs

: In the last 20 years, N-heterocyclic carbene (NHC) ligands have been ubiquitous in biological and medicinal chemistry. Part of their success lays in the tremendous number of topologies that can be synthesized and thus finely tuned that have been described so far. This being particularly true in the case of those derivatives including fluorine or fluorinated fragments on their NHC moieties, attracting much attention due to their enhanced biological properties and turning them in excellent candidates for the development of novel metallodrugs. Thus, this review summarizes the development that fluorinated-NHC transition metal complexes have had and their impact in cancer treatment.

Metalloproteomics for molecular target identification of protein-binding anticancer metallodrugs

The development of the metallodrug pull-down as a metalloproteomic technique has enabled the identification of the protein targets of metal-based anticancer agents.

Unconventional Anticancer Metallodrugs and Strategies to Improve Their Pharmacological Profile

For the past 41 years, metal-based drugs have been widely used for the treatment of cancer [...]