Challenges and Opportunities in Developing Biologically Active Copper Complexes as Metal-based Drugs

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Background

The evolution of diseases in the last few decades requires a diversification of treatment approaches. For instance, bacterial infections are more and more resistant to treatment with antibiotics or are hard to treat as result of their complication with biofilms. On the other hand, cytostatics used in the current treatment of cancer are expensive and generate resistance. Moreover, there is a lack of drugs for the treatment of diseases such as mellitus diabetes, viral and parasitic infections, or inflammatory conditions. As result, new drugs or their formulations are required for these affliction’s treatment, involving either complexes as an active species, or a proper delivery method for an enhanced effect. To this purpose, copper complexes provide a huge platform since both their chemical and biological properties can be fine-tuned by a proper selection of ligands. Hence, there is a continuous interest in designing new copper complexes with various biological properties, as well in finding a proper route for administration whilst preserving these properties in vivo.

Although there are some metal-based drugs involved in cancer, rheumatoid arthritis, and microbial infection treatment, their widespread use is limited due to severe side effects, toxicity and resistance. Moreover, in the last few years, some biologically active Cu(II) complexes entered into clinical trials, but only a few were developed as drugs. For many of them, their limitations come from a low stability in biological mediums or an unfavorable ratio between lipophilicity and water solubility. As a result, the challenges in the field exist both in the design of complexes with a good biological activity and a low toxicity and/or in finding a proper route for their administration whilst keeping this activity in vivo. Nevertheless, there are numerous opportunities in the field, such as proper selection of ligands mixture, the rational design of a Cu(II) complex either for a selective delivery, or for a specific interaction with a biomolecule and/or for a proper embedding in a biocompatible matrix. All of these will ensure an enhanced and selective interaction with target biomolecule and thus a great efficacy assisted by a low toxicity. The potential use of Cu(II) complexes for the treatment of viral infections, neurodegenerative and inflammatory diseases also represent an opportunity to develop new drugs based on this metallic ion.

This Research Topic aims to provide insight in developing copper complexes with a good biological activity (anti-tumor, antimicrobial, antiviral, anti-inflammatory etc.) and low toxicity, or a proper carrier system for these species delivery. Papers focused on the fully characterized copper complexes by single crystal X-ray diffraction are highly desirable.

To this end, we welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:
• Biologically active Cu(II) complexes for overcoming resistance
• Copper complexes with anti-biofilm activity
• Rational design of Cu(II) complexes for a selective interaction with a target biomolecule
• Improvement of biological activity by Cu(II) species (including Cu, Zn-SOD, Casiopeinas, Chlorophyllin) embedding in an organic or inorganic matrix
• Stimuli-responsive systems based on Cu(II) complexes
• Complexes of Cu(II) with multiple modes of interactions with biomolecules

Keywords: copper complex, resistance, biofilm, carrier, target biomolecule, drug design

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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