Exploration of the medical periodic table: towards new targets

Abstract

Metallodrugs offer potential for unique mechanisms of drug action based on the choice of the metal, its oxidation state, the types and number of coordinated ligands and the coordination geometry. We discuss recent progress in identifying new target sites and elucidating the mechanisms of action of anti-cancer, anti-bacterial, anti-viral, anti-parasitic, anti-inflammatory, and anti-neurodegenerative agents, as well as in the design of metal-based diagnostic agents. Progress in identifying and defining target sites has been accelerated recently by advances in proteomics, genomics and metal speciation analysis. Examples of metal compounds and chelating agents (enzyme inhibitors) currently in clinical use, clinical trials or preclinical development are highlighted.

Interactions of arene ruthenium metallaprisms with human proteins

“…These complexes selectively bind to proteins or inhibit enzymes known to be overexpressed in many types of cancer. 7,[9][10][11][12][13] To date, much work has been done to elucidate the mode of action of various ruthenium-based drug candidates, 14,15 but the way they exert their antitumoural or antimetastatic effects is not yet fully understood, even for NAMI-A and NKP-1339, which have successfully completed clinical trials. 14,[16][17][18] By analogy with platinum complexes, it was originally assumed that DNA binding was the main reason for the anticancer activity of ruthenium complexes.…”

Evaluation of Perylene Bisimide‐Based RuII and IrIII Complexes as Photosensitizers for Photodynamic Therapy

“…[16][17][18][19][20][21][22][23][24][25][26] Besides ruthenium, [27][28][29][30][31][32] other metals, such as iridium(III), rhenium(I), [33][34][35][36][37][38] Fe III , [39] Co III , [40] and Gd III [41] have been investigated by us and other groups in regard to traditional chemotherapy and PDT applications. [42][43][44][45] Compared with the Ru complexes, less effective PDT agents based on Ir compounds have been reported so far, probably because of the difficulties in suppressing the competing electron-transfer processes. [46] Nevertheless, several Ir III compounds, most commonly bearing cyclometalated ligands, have recently been found to be promising PDT agents.…”

On the binding modes of metal NHC complexes with DNA secondary structures: implications for therapy and imaging

“…3,47 The earliest examples of direct interactions between metallodrugs and DNA stem from platinum(II)…”