Synthesis, characterization, DNA interaction, and anticancer studies of novel facial tricarbonylrhenium(i) complexes...

Herein, we report the formation and characterisation of novel rhenium(i) complexes with bidentate uracil chelating ligands. Three metal complexes including fac-[Re(CO)₃(urda)Cl] (1) (urda = 5, 6-diamino-1, 3-dimethyluracil), fac-[Re(CO)₃(uramb)Br] (2) (uramb = amino-5-((2-aminobenzylidene)amino)-1,3-dimethyluracil) and fac-[Re(CO)₃(urqn)Br] (3) (urqn = amino-5-((isoquinolin-3-ylmethylene)amino)-1,3-dimethyluracil) were spectroscopically characterized. Structural elucidations were corroborated by single-crystal X-ray crystallography, TOF mass spectrometry, and elemental analysis. These metal complexes retain their structural integrity in aqueous media during UV-Vis spectrophotometric titrations. Anticancer screening of the metal complexes was done in two cancer cell lines, HCC70 and HeLa, as well as in a benign MCF12A cell line. In particular, while complex 1 was highly cytotoxic towards HeLa cells and was non-toxic to HCC70 TNBC and MCF12A non-cancerous cells, complex 2 displayed low micromolar toxicity in all three cell lines and was selected for further analysis. This metal complex exhibits dual DNA intercalation and groove-binding modes, however this did not lead to DNA damage as assessed by a comet assay. In addition, metal complex 2 did not appear to inhibit topoisomerase activity, suggesting a different mechanism of action from that reported for ruthenium complexes with topoisomerase inhibitory activities.