Essential Metal-based drugs: Correlation between Redox Potential and Biological Activity of M2+ with a N2O2 Ligand

Abstract

One of the major public health problems worldwide is cancer followed by a significant number of deaths due to the resistance developed by bacteria or protozoan to the currently employed treatments. This generates an immediate need to develop drugs to treat these afflictions (illnesses, diseases). It has recently been identified that tumor cell, bacteria or protozoa are quite sensitive to oxidative stress induced by the same drugs. Due to this, it is important to develop new drugs to attend them, in this case, by using metals to increase the concentration of oxidative species. In the present work, the ligand 2,9-diformyl-4,7-diphenyl-1,10-phenanthroline and its corresponding coordination compounds with essential metals such as iron(II), cobalt(II), nickel(II), copper(II) and zinc(II) were synthesized. The electrochemical study shows that these compounds present three redox processes, all of them associated to the ligand. The compounds have shown inhibitory activity in vitro against human neuroblastoma CHP-212 cells, Escherichia coli and trophozoites of Entamoeba histolytica HM1:IMSS. It has been found that the inhibitory activity of the compounds studied is related to the first reduction process of the ligand. The correlation between the inhibitory activity and the red ox potential was linear. The inhibitory activity in CHP-212 increased with the increase of the compounds’ redox potential values, in contrast with the behavior observed in Escherichia coli, where the compounds with lowest redox potential values have had significantly higher inhibitory activity. Many of these coordination compounds have shown a higher inhibitory activity than those typically used in the treatment of cancer (cisplatin). The next step is to prove these compounds in vitro against healthy cells in order to verify its selectivity or cytotoxicity in these systems.