Second and third-row transition metal compounds containing benzimidazole ligands: An overview of their anticancer and antitumour activity

The application of metal compounds in the medical field dates back to the XVI century with some isolated reports about the therapeutic importance of metals and their compounds in the treatment of various diseases, including cancer. Nowadays, the number of commonly prescribed metal-containing compounds is very broad and includes antimony (antiprotozoal), bismuth (antiulcer), iron (antimalarial), gold (antiarthritic), silver (antimicrobial), platinum (anticancer), and vanadium (antidiabetic), among others. Most biological molecules, such as DNA or proteins, are rich in electron density, while metal ions lack electrons. For that reason, we can observe a marked trend in which metal ions interact with various molecules of biological interest. Furthermore, metal ions also have a great affinity for various tiny molecules, such as molecular oxygen, which are essential to life. During the last sixty years, several classes of new metal derivatives, mainly organometallic and coordination compounds have been intensively investigated as possible anticancer and/or antitumour agents based on a great variety of metals, mainly from the d-block. Therefore, we previously reported a thorough bibliographic review of the cytotoxic and/or antiproliferative activity of the coordination compounds of the first transition series that contained benzimidazole ligands in their composition and structure https://doi.org/10.1016/j.ccr.2021.213930. In the same sense, in this work we expand our analysis to include the metals of the second and third transition series, hoping that this document will help in the choice of the appropriate ligands and metals for the design of new, more efficient, and selective metallodrugs. The main findings found in this review showed that the factors that we must consider in the design of coordination complexes with chemotherapeutic properties are: solubility, molecular structure and geometry, the global charge of the complex, the appropriate choice of the benzimidazole ligand considering the substituents or functional groups in its structure as well as the chirality conferred by its precursors; the appropriate choice of the metal centre considering its atomic radius, electronic configuration and oxidation state, it is even important to consider the use of co-ligands with guaranteed biological activity. These and other aspects related to the structure and activity of the compounds will be analysed below.