Abstract
The present project centers on the synthesis of complexes of ruthenium (II) containing lapachol and lawsone bioligands, which may present the following formulas: [Ru(L-L)(bipy)(dppf)]PF6, [Ru(L-L)(bipy)(dppe)]PF6 and [Ru(L-L)(dppe)2]PF6, where L-L = lapachol and lawsone, bipy = 2,2'-bipyridine, dppf = 1,1'-bis(diphenylphosphino)ferrocene and dppe = 1,2'-bis (diphenylphosphino)ethane. The complexes obtained will be evaluated for their cytotoxic activity in cell lines of breast cancer (MCF-7), prostate (DU-145), lung (A549), normal mouse fibroblasts (L929) and human (FH), and those that perform best will be submitted to further studies seeking determine the mechanism of action of the same. Initially the interaction of the complexes with DNA and BSA will be evaluated. Subsequently will be analyzed membrane integrity, mitochondrial depolarization, cell cycle, apoptosis assay by annexin V, caspase activity quantification and reactive oxygen species, and determination of apoptosis-related proteins by the technique of Western blotting. Eventually, by means of chemical and biological data, the aim is verify whether there is any correlation between structure and activity, as well as a possible mechanism of action. Similar to the above-mentioned compounds with general formulas [Ru(L-L)(dppb)(N-N)]PF6 and [Ru(lawsone)(PPh3)2(N-N)]PF6 (where dppb = 1,4-bis (diphenylphosphino)butane, PPh3 = triphenylphosphine and NN = 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine or 1,10-phenanthroline) obtained, characterized and tested against MCF-7 cell line in the master the candidate may also be used in the development of this project. (AU)
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