Background: In this review article a brief overview of novel metallotherapeutic agents (with an emphasis on the complexes of essential biometals) promising for medical application is presented. We have also focused on recent work carried out by our research team, specifically the development of redox-active antimicrobial complexes of sterically hindered diphenols with some essential biometals (copper, zinc, nickel). Results: The complexes of essential metals (manganese, iron, cobalt, nickel, copper, zinc) described in the review show diverse in vitro biological activities, ranging from antimicrobial and anti-inflammatory to antiproliferative and enzyme inhibitory. It is necessary to emphasize that the type of organic ligands in these metal complexes seems to be responsible for their pharmacological activities. In the last decades there has been a significant interest in synthesis and biological evaluation of metal complexes with redox-active ligands. A substantial step in the development of these redox-active agents is the study of their physico-chemical and biological properties, including investigations in vitro of model enzyme systems, which can provide evidence on a plausible mechanism underlying the pharmacological activity. When considering the peculiarities of the pharmacological activity of the sterically hindered diphenol derivatives and their nickel(II), copper(II) and zinc(II) complexes synthesized, we took into account their being potential antioxidants, their antimicrobial activity possibly resulting from their affecting the electron-transport chain. Conclusion: We have obtained novel data demonstrating that the level of antibacterial and antifungal activity in the series of the above-mentioned metal-based antimicrobials depends not only on the nature of the phenolic ligands and complexing metal ions, but also on the lipophilicity and reducing ability of the ligands and metal complexes, specifically regarding the potential biotargets of their antimicrobial action – ferricytochrome c and the superoxide anion radical. The combination of antibacterial, antifungal and antioxidant activity allows one to consider these compounds as promising substances for developing therapeutic agents with a broad spectrum of activity.

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