Unveiling the Potential of Transition Metal Complexes for Medicine: Translational in Situ Activation of Metal‐Based Drugs from Bench to in Vivo Applications

Abstract

The development of metal-based anticancer drugs has been hampered, among other reasons, by their lack of selectivity for cancer cells. In a recent article, Zou and co-workers presented the successful intracellular activation of organogold(I) complexes for potential cancer treatment through Pd(II)-mediated transmetallation, overcoming some off-target activity of novel gold-based drugs. This unique strategy builds the perfect bridge between metallodrug usage and bioorthogonal intracellular catalysis for more advanced and selective therapies. Such an approach will hopefully pave the way for forthcoming studies in medicinal inorganic chemistry.

Indole-containing arene-ruthenium complexes with broad spectrum activity against antibiotic-resistant bacteria

“…( Barry and Sadler, 2013 , Barry and Sadler, 2014 ) As such, medicinal inorganic chemistry provides a rich platform in the pharmacological space for structural and electronic diversity. ( Silva et al., 2021 ) Medicinal inorganic chemistry has been stimulated by the success of platinum anticancer drugs (used as a component of nearly 50% of all cancer chemotherapy treatments), by the use of gadolinium(III) complexes as MRI contrast agents (about 20 million doses administered per year), and of the radionuclide 99m-technetium radiopharmaceuticals for γ-ray imaging (used in about 20 million radio diagnostic procedures each year). ( Biancalana et al., 2020 , ( Farley et al., 2021 ), Hanif et al., 2020 , Rafols et al., 2021 ) However, the involvement of metals in many other diseases and conditions is of current interest in relation to their causes, their treatment or detection, including neurodegeneration, ( Anthony et al., 2020 ) fungal ( Golbaghi et al., 2020 ), parasitic, ( Minori et al., 2020 , Melis et al., 2021 ) viral ( Yuan et al., 2020 ) infections and inflammation.…”

Facing Diseases Caused by Trypanosomatid Parasites: Rational Design of Pd and Pt Complexes With Bioactive Ligands

“…However, the discovery of the potent anti-tumor activity of cisplatin, [PtCl 2 (NH 3 ) 2 ] determined the beginning of the modern era of Medicinal inorganic chemistry, accompanied by a huge impact of metal compounds in modern medicine. By exploiting the unique properties of metal ions, Medicinal inorganic chemistry currently offers an attractive option for the rational design of new drugs, looking for defined targets and activities, and new diagnostic and theranostic tools (Zhang and Sadler, 2017;Hanif and Hartinger, 2018;Englinger et al, 2019;Kostelnik and Orvig, 2019;Soldevila-Barreda and Metzler-Nolte, 2019;WahsnerGale et al, 2019;Wang et al, 2019;Anthony et al, 2020;Chamberlain et al, 2020;Chellan and Sadler, 2020;Imberti et al, 2020;Murray and Dyson, 2020;Cirri et al, 2021;Karges and Cohen, 2021;Lin et al, 2021;Silva et al, 2021;Yousuf et al, 2021). In the last decades, the development of metal-based drugs has proven to be a promising approach in the search for new therapeutic tools against parasitic diseases.…”

Strategies to promote permeation and vectorization, and reduce cytotoxicity of metal complex luminophores for bioimaging and intracellular sensing

“…4 This has been driven in large part by creative solutions to the longstanding problems of poor permeation of coordination compounds through the cell membrane. [5][6][7][8][9] In many cases these solutions are inspired by strategies employed in the pharmaceutical industry to promote membrane permeability of therapeutics and their delivery to intracellular targets. In eukaryotic organisms, cell permeation of exogenous species can occur via passive and/or active transport or through vesicle mediated mechanisms, the latter are also activated mechanisms.…”