Metal-based pharmaceuticals (metallodrugs) are one of the main research areas in the field of bioinorganic chemistry. Metallodrugs have drawn great attention for their value as therapeutical and diagnostic agents for cancer, bacteria, diabetes, Alzheimer’s Disease, Parkinson’s Disease, and others. For instance, platinum based anticancer agents are among the most widely used drugs and included in the WHO’s list of essential medicines. However, limitations, such as their side effects and drug resistance, appeared and promoted the development of new, ‘smarter’ metallodrugs. Recently, medicinal chemists and pharmacologists have been focusing on the design of transition metal anticancer agents that might be effective against a wider range of cancers, have less side effects, have different mechanisms of action, and therefore be effective against platinum-resistant cancers. Metallodrug researchers have devoted tremendous efforts to overcome drug resistance and to find new cures with higher selectivity.

By rational design around the metal center and its coordinating ligands, efficient metallodrugs could be created. In most cases, both the metal ions and ligands play important roles in the modes of action. Sometimes even a change of one atom in the chemical configuration of a metallodrug might cause significant differences in the chemical and biological properties. For example, the anticancer activity of organoiridium complexes could be improved over 1000 times by introducing phenyl or biphenyl substituents on a Cp* ring, replacing a nitrogen atom with a carbon atom in a bipyridine ligand, and by substituting chlorido ligands with pyridine. It is absolutely essential to fully understand to the fate of the metal and the ligands once the metallodrug enters the body, where the majority of metallodrugs would undergo ligand exchange. The mechanisms of action may include interactions with nucleic acids or proteins/enzymes, even catalyzing transfer hydrogenation in cells or generating reactive oxygen species. Multifunctional metallodrugs are highly desired as they have more than one way to fight against a disease and cancer cells may find it harder to develop resistance. Metal complexes could target one or more organelles according to their modes of action, which demands a significant effort into designing, synthesizing, and evaluating their biological properties. A clear look into the mode of action is crucial to understand the performance of metallodrugs, and it feeds back positively into the design of new drugs.

This current Research Topic aims to exploit fully the potential of metallodrugs and to present the reader with the latest progress of metallodrugs in the discipline of medicinal inorganic chemistry. Submissions focusing on all aspects of metallodrug development are welcome. Areas to be covered in this Research Topic may include, but are not limited to:

• Metal-based anticancer therapy
• Alzheimer Disease and Parkinson Disease therapeutics related to metals
• Exploration of the function procedure and studies of mechanisms of action
• Metal complexes exhibiting organelle targeting ability or cell selectivity
• Metal related luminescent probes
• Photochemotherapeutic metallodrugs
• Studies on the ADME properties of metallodrugs, that is, absorption, distribution, metabolism, and excretion
• Mode of action studies
• The development of new tools to investigate the modes of action
• Metallomics and metalloproteomics

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Frontiers in Chemistry

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