Strategies for the Improvement of Metal-Based Chemotherapeutic Treatments

Abstract

This article provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic anticancer drugs is a very slow process. Analogously, although a few promising inorganic drugs have found clinical application against parasitic or bacterial infections, their use remains relatively limited. Moreover, the discovery process is often affected by small therapeutic enhancements that are not attractive for the pharmaceutical industry. However, the availability of increasing mechanistic information for the modes of action of established inorganic drugs is fueling the exploration of various approaches for developing effective inorganic chemotherapy agents. Through a series of examples, some from our own research experience, we focus our attention on a number of promising strategies, including (1) drug repurposing, (2) the simple modification of the chemical structures of approved metal-based drugs, (3) testing novel drug combinations, and (4) newly synthesized complexes coupling different anticancer drugs. Accordingly, we aim to suggest and summarize a series of reliable approaches that are exploitable for the development of improved and innovative treatments.

Molecular Pathogenesis of Colorectal Cancer with an Emphasis on Recent Advances in Biomarkers, as Well as Nanotechnology-Based Diagnostic and Therapeutic Approaches

“…Oxaliplatin is the third generation of the DACH platinum compound. Oxaliplatin is successful in the treatment of colorectal cancer, but platinum compounds cisplatin and carboplatin have been shown to be ineffective [ 110 ]. It is frequently used to treat patients who have not responded to 5-fluorouracil (5FU)-based therapy.…”

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

“…This means that Pd(II) compounds are much more reactive in solution which could lead to a higher toxicity and a different biological behaviour. However, the adequate selection of ligands could be able to stabilize Pd(II) complexes affecting their reactivity and imparting substitution inertness (Jahromi et al, 2016;Lazarević et al, 2017;Cirri et al, 2021;Czarnomysy et al, 2021;Yousuf et al, 2021).…”

“…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.…”

In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study

“…Several gold, bismuth, antimony, and mercury compounds have been used to treat a variety of diseases, mostly infectious ones, including tuberculosis and syphilis, and many parasitic diseases. Even arsenicals, despite being real poisons, were employed in clinics at low doses for various therapeutic purposes with some positive results [ 5 , 6 , 7 ].…”