Ruthenium complexes of ferrocene mannich bases: DNA/BSA interactions and cytotoxicity against A549 cell line

Two different series of ruthenium complexes, ML3 and MLL2' where M=Ru(III)/Ru(II), L = ferrocenyl amino acid mannich base conjugates and L' = 1,10-phenanthroline have been synthesized and characterized by spectroscopic methods. These ferrocenyl ligands and their ruthenium complexes have been investigated for their interactions with DNA and BSA (bovine serum albumin) employing steady-state fluorescence quenching measurements, UV-vis spectroscopy and DNA viscosity measurements. High binding constants obtained from the DNA binding studies (K-b = 10(4) - 10(6)M(-1)) prompted the in-vitro cytotoxicity assay of complexes on A549 human lung carcinoma cells (employing MIT assay). The IC50 values (within the range of 46 mu M-422 mu M) obtained herein were found to be lower than those of the well known ruthenium complex NAMI-A currently under phase II clinical trials which has IC50 values in the range of 550 mu M-750 mu M for various cancer cell lines. Interaction of these complexes with A549 cells has been further scrutinized using acridine orange (AO)/ethidium bromide (EB) dual staining technique to indicate apoptosis as the mode of cell death. (C) 2015 Elsevier B.V. All rights reserved.