Editorial [Hot topic: Metal-Containing Drugs and Novel Coordination Complexes in Therapeutic Anticancer Applications - Part II (Guest Editor: Irena Kostova)]

While cancer remains a major killer in the developed world, a broad spectrum of novel and exciting approaches are being developed and tested. The importance of metal compounds in medicine is undisputed, as can be judged by the use of many metal-based compounds in the treatment of various diseases. In terms of anti-tumour activity, a wide range of compounds of both transition metal and main group elements have been investigated for efficacy. The existence of a relationship between cancer and metals is widely acknowledged by researchers. Therefore, the aim of the theme issue “Metal-Containing Drugs and Novel Coordination Complexes in Therapeutic Anticancer Applications” of Anti-Cancer Agents in Medicinal Chemistry is to present an up-to date overview of this subject and to cover very recent developments in the field of metal-based anticancer agents. Recent advances in medicinal inorganic chemistry demonstrate significant prospects for the utilization of metals and their coordination complexes as drugs, presenting a flourishing arena for inorganic chemistry. Significant progress in metal-based agents has been achieved. Nevertheless, there is an urgent need for new drugs to treat cancer, drugs with novel mechanisms of action. Metal complexes appear to provide a rich platform for the design of novel anticancer drugs. The metal, its oxidation state, the number and types of coordinated ligands, and the coordination geometry of the complexes can provide variety of properties. On the other side, the ligands can not only control the reactivity of the metal, but also play critical roles in determining the nature of interactions involved in the recognition of biological target sites, such as DNA, enzymes and protein receptors. These variables provide enormous potential diversity for the design of metallodrugs. They also introduce many challenges. Changes in composition are likely to be accompanied by changes in the respective biological activity. Hence it is important to identify the nature of the metal complex which exists in the biological medium and is undergoing the biological test, and ideally the species which reaches the target site. There is now no doubt that medicinal inorganic chemistry, and metal coordination chemistry in particular, is worthy of exploration for drug design. Developing metal complexes as drugs, however, is not an easy task. Accumulation of metal ions in the body can lead to deleterious effects. Thus biodistribution and clearance of the metal complexes as well as its pharmacological specificity are to be considered. Favourable physiological responses of candidate drugs need to be demonstrated by in vitro study with targeted biomolecules and tissues as well as in vivo investigation before they enter clinical trials. A mechanistic understanding of how metal complexes achieve their activities is crucial to their clinical success, as well as to the rational design of new compounds with improved potency. In the first part of the Special Issue “Metal-Containing Drugs and Novel Coordination Complexes in Therapeutic Anticancer Applications” timely in-depth reviews are given. The first and this second part of the issue focused on recent advances in developing different metal-based anticancer agents, on recent efforts to prepare novel platinum, ruthenium, gold, titanium, selenium etc. complexes and reviewed some mechanistic insights into the pharmacological effects of these complexes. It is well known that for the perspective of metal-based drugs, some results are encouraging, but some others challenging. Firstly, the clinical success of a drug candidate depends not only on its bioactivity, but also on the absorption, distribution, elimination, metabolism and toxicity properties. These qualities are determined by the structure of the compound and also by external factors. The second difficulty is related to the activity/toxicity modulation. The next problem worth to be studied is the cell response to the metals. Differing from organic drugs, metals act on several key points in the life process. Thus they intervene with a pathological process from a number of targeting points. To this end, the scientists have to study the input and output relation and establish quantitative models to describe the effects of cell responses to different metals. It needs no discussion that the above-presented highlights and outlook about metal-based therapeutics provide fascinating new possibilities for research in the coming decades. It is generally appreciated that enormous progress has been made in the understanding of the mode of action of the most of metal-based agents. Application of this knowledge in drug design is close, and it is generally expected that in the next decades improved drugs will be developed based on this knowledge. The future development of medicinal inorganic chemistry of metals requires an understanding of the physiological processing of metal complexes, to provide a rational basis for the design of new metal-based drugs. Application of new methodologies such as combinatorial chemistry, extensively used in drug discovery, will be beneficial for the study of various metals and the development of their coordination complexes as therapeutics....