Emerging metal-organic anticancer compounds: synthesis and biological activity of novel Ga(III) and Ru(II) complexes

Cancer is described as a collection of life-threatening diseases due to an uncontrolled division of abnormal cells. 1 Because of the failure of growth or division regulatory system, the affected cells can proliferate boundlessly and colonize other tissues normally reserved for other type of cells. Despite decades of clinical research and trials of promising new therapies, cancer remains the principal cause of death in the world, with approximately 19.6 million of new cases every year. For this reason, the scientific community is now focusing on the development of novel effective treatments. The choice of the therapeutic option depends upon the cancer type and the stage of the disease, as well as the general condition of the patient. While recognizing the success of traditional therapeutic approaches, such as radiotherapy, and innovative ones, like gene therapy and regenerative medicine, it is easy to predict that the pharmacological approach will continue to be a fundamental tool in the fight against cancer. Even if its discovery dates back to 1960 by Barnett Rosenberg , cisplatin remains the front-line medication prescribed for the treatment of multiple cancers. Specifically, the cisplatin-treated cancers are attenuated with the suppression of tumorigenesis and metastases, thus limiting the progression of the disease. However, the onset of drug resistance phenomena and the significant adverse effects of cisplatin had led the research to focus its attention on the development of novel anticancer agents able to overcome the problems associated with the use of the drug. In the wake of the success of cisplatin, pharmaceutical research is increasingly oriented towards the study of metal-organic complexes for the treatment of cancer. Their therapeutic potential has attracted a lot of interest mainly because metals exhibit unique characteristics, such as redox activity, variable coordination modes and reactivity toward the organic substrate. In particular, the main goal of bioinorganic chemistry is the ligand substitution and modification of existing chemical structures, leading to the synthesis of a wide range of new metal-based compounds, some of which have demonstrated an enhanced cytotoxic and pharmacokinetic profile. Moreover, in the last decade, a different approach to antitumoral drug design has been adopted: it involves the conjugation of metallic compounds to endogenous organic molecules, such as peptides, sugars or steroids, in order to specifically target the cancer cells and consequently secure the drug delivery directly to the interested site, avoiding some pharmacokinetic challenges.