Potential cytotoxic and amoebicide activity of first row transition metal compounds with 2,9-bis-(2′,5′-diazahexanyl)-1,1-phenanthroline (L1)

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 metal ions Mn, Fe, Co, Ni, Cu and Zn. Complete characterization of all compounds was done with the conventional techniques. Crystal structures of [NiL1](PF6)(2) and [ZnL1](PF6)(2)center dot H2O were also reported. Electrochemical studies have shown an active participation of the aromatic moiety of the ligand in redox reactions. The in vitro tests of the cytotoxic activity against human tumour cell lines HeLa (cervix) and CHP-212 (neuroblastoma) showed that all coordination compounds that involve redox active metal ions exhibit noteworthy antiproliferative activity, superior in all cases to cisplatin. [CuL1](2+) showed the lower IC50 value in the HeLa cell line with 1.84 mu M, meanwhile, [CoL1](2+) showed the lower value in neuroblastoma CHP-212 with IC50 = 45.28 mu M. None of these compounds were active against the SK-N-SH neuroblastoma cell line. In Entamoeba histolytica cultures, remarkable nanomolar IC50 values were found for [NiL1](2+) and [MnL1](2+) with 60 nM and 80 nM respectively, improving the antiproliferative activity more than 1000 times compared with the first choice drug for clinical treatments of human amoebiasis, metronidazole. On the other hand, a free ligand does not show antiproliferative activity either on human tumor cell lines or on Entamoeba histolytica trophozoites, highlighting the role played by metal ions to produce cytotoxicity in tumor cells and protozoa systems.