A comparative study of novel ruthenium(III) and iron(III) complexes containing uracil; docking and biological studies

Structural and biological studies were conducted on the novel complexes [Fe(U)2(H2O)2]Cl3 (FeU) and [Ru(U)2(H2O)2]Cl3 (RuU) (U = 5,6-Diamino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione) to develop an anticancer drug candidate. The two complexes have been synthesized and characterized. Based on our findings, these complexes have octahedral geometry. The DNA-binding study proved that both complexes coordinated with CT-DNA. The docking study confirmed the potency of both complexes in downregulating the topoisomerase I protein through their high binding affinity. Biological studies have established that both complexes can act as potent anticancer agents against three cancer cell lines. RuU or FeU complexes induce apoptosis in breast cancer cells by increasing caspase9 protein and inhibiting proliferating cell nuclear antigen (PCNA) activity. In addition, both complexes down-regulate topoisomerase I expression in breast cancer cells. Therefore, the RuU and FeU complexes' anticancer activities were mediated via both apoptosis induction and topoisomerase I down-regulation. In conclusion, both complexes have dual anticancer activity pathways that may be responsible for the selective cytotoxicity of the complexes. This makes them more suitable for the development of novel cancer treatment strategies. FeU and RuU complexes decrease topoisomerase I expression and induce apoptosis via proliferating cell nuclear antigen (PCNA) and caspase 9 regulation. [Display omitted] •Novel Ru(III) and iron(III) complexes containing uracil were synthesized as anticancer drug candidates.•Docking's study confirmed that both complexes block the topoisomerase I (TOPO I) protein.•In vitro study proves that both complexes were potent against three cancer cell lines.•RuU or FeU complexes induce apoptosis in breast cancer cells (MCF-7), as well as down-regulating TOPO I.•FeU lower cost and higher availability could make it a more attractive option for researchers and clinicians.