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Metal complexes have gained a growing interest as pharmaceuticals for their use as diagnostic agents or as chemotherapeutic drugs. In our group some efforts have been done in the development of anticancer agents employing essential metals such as the family of copper (II) compounds known as Casiopeínas®, with a general formula [Cu (N-N) (X-Y) H2O] NO3 where N-N is a diimine (phen or bipy) and X-Y is a bidentate ligand (acac, salal, aminoacidate, peptide, benzimidazol). These compounds have shown cytostatic, cytotoxic and antineoplastic activity in vitro and in vivo. Comparison between first and second generation of casiopeina´s activity is presented. Also albumin/Casiopeinas interaction is discussed.
The mechanism of action is still not completely elucidated. However, experimental evidence suggests the interaction of coordination compounds with DNA (nuclear or mitochondrial) and their components and the generation of reactive oxygen species (ROS) as the main action pathways. Induction of apoptosis has been proved to be the main death tumoral cell pathway.
DNA interaction has been done by several methods, comet assay, AFM, electrophoresis, CD and the nuclease activity studies of 4 Casiopeínas® employing plasmidic DNA in several reaction conditions is presented, microarray.
Comparison of the results shown that compounds with 4,7-dimethyl phenanthroline in the copper (II) coordination sphere have an extraordinary DNA cleavage capacity, compared with the 4,4´-diimine analogs, then is suggested a intercalation process as the first step for the DNA damage. Also calculations have been done in order to modeling the interaction between Casiopeínas and DNA.
Also a new synthetic pathway was reported to obtain N6 donor ligand 2,9-Bis-(2’,5’-diazahexanyl)-1,10-phenanthroline (L1) and its coordination compounds of essential divalent