Editorial [Hot Topic: Metal Containing Complexes with Anticancer Properties (Guest Editors: A. Nazarov & C. Hartinger)]

The general concept of chemotherapy was introduced by Ehrlich about a century ago in which a systematic variation of structures and studies on the biological activity of antimicrobials resulted in the development of salvarsan. The concept has been followed by researchers all over the world and numerous compounds have been screened for other medicinal applications since Ehrlich's pioneering work, including many for their tumor-inhibiting properties. The approach of relating structural changes with biological activity was also successful in the quest for anticancer chemotherapeutics and several classes of anticancer compounds are available now, among which platinum compounds are some of the most widely used drugs. For the latter compound group, Ehrlich's approach was applied after the development of cisplatin as a lead structure, and has been followed since by many individual contributors rather than a single research group. In recent years, the metal-based anticancer research community has designed compounds that exhibit new modes of action, and in particular, breaking the paradigm of maintaining “platinum-type” structural motifs and mechanisms. In this issue of Current Topics in Medicinal Chemistry on “Metal-based Compounds in Anticancer Research” we have aimed to collate reviews to give the reader an idea of some of the current strategies applied. Furthermore, the number of used bioanalytical/biophysical and molecular biology methods is steadily increasing, providing better insight into the modes of action of chemotherapeutics, as highlighted in some of the contributions to this special issue. At the same time, we acknowledge that it was not possible to cover all topics in this issue of Current Topics in Medicinal Chemistry due to space restrictions. In this context, reviews on topics covering a wide range of approaches in drug discovery for cancer chemotherapy have been included in this issue. This comprises newer developments in platinum drugs, such as Pt(IV) prodrugs which are reviewed by Wee Han Ang, Ramasamy Jothibasu and Mengtao Ma with special consideration of prodrug strategies, photodynamic therapy and drug targeting. Adoracion G. Quiroga describes the properties of non-classical Pt complexes to overcome current limitations of Pt-based anticancer agents, also mediated by the ligands coordinated to the metal center, and catalytic processes induced by metal complexes in biological fluids. The form of administration of drug compounds to living systems is of crucial importance in controlling the pharmacokinetic properties of drug substances. Nicholas P. Farrell introduces the reader to different formulations of established platinum anticancer chemotherapeutics for drug delivery. As important as formulation of a drug candidate, is the identification of its molecular target. In this context, Michael Groessl and Paul J. Dyson review bioanalytical/ biophysical techniques and critically discuss their strengths and limitations, and illuminate the information accessible from these techniques. The application of several of these techniques to identify the molecular mechanisms and targets of anticancer gold compounds is the topic of the contribution by Angela Casini and Luigi Messori. Likewise, Iztok Turel and Jakob Kljun describe the role of anticancer metallodrug binding to DNA, being known as the crucial factor in the anticancer activity of the clinically-used platinum drugs, and different DNA binding modes of metal ions, and in this respect they also discuss the treatment of other diseases and imaging applications. Andrew D. Phillips, with us, summarizes some of the recent contributions to the field of polynuclear and some non-platinum species with tumor-inhibiting properties, with a special focus on the comparison of anticancer properties of the polynuclear compounds and their mononuclear analogues. However, as important as the treatment of cancer might be, is the prevention of cancer. One factor which contributes to carcinogenesis is oxidative stress and Elena R. Milaeva summarizes recent research on potential therapeutic candidates as antioxidants with ROS scavenging properties. As can be seen from the topics covered, there is another lesson that can be learned from Ehrlich's research, namely that a team effort is most efficient to develop a new drug. This fact is even more relevant in modern times with the requirements established by federal drug agencies for the introduction of drugs to the market. Only joint efforts of synthetic and analytical chemists, biologists, pharmacists, medical doctors and industrial partners will result in the marketing of new drugs. The researchers in the field of metal-based drugs have a filled pipeline with promising compounds available for the treatment of different diseases, just waiting for further development. Finally, we would like to thank all the contributing authors of this issue and the referees for their valuable contributions. We hope that the readers will appreciate the selection of reviews and that this special issue will stimulate discussion within the research field and attract groups with complementary areas to join forces to fight cancer.