Deoxyribonucleic acid (DNA) and bovine serum albumin (BSA) binding interactions for a series of ruthenium heterocyclic complexes were monitored using ultraviolet-visible (UV-Vis) spectrophotometry, fluorescence emission spectroscopy and agarose gel electrophoresis. Investigations of the DNA interactions for the metal complexes revealed that they are groove-binders with intrinsic binding constants in the order of 10⁴ – 10⁷ M⁻¹. Electronic spectrophotometric DNA titrations of the bis-heterocyclic metal complexes illustrated hypochromism of their intraligand electronic transitions and the presence of diffuse isosbestic points which are synonymous with homogeneous binding modes. Metal complexes with the mono-heterocyclic chelates also showed alterations in their intraligand transitions and changes in their metal-based electronic transitions which are suggestive of metal coordination to the CT-DNA structure. Using agarose gel electrophoresis assessments, Hoechst DNA binding competition studies corroborate that the metal complexes are DNA groove-binders. Optimal uptake of these metal complexes by BSA was observed based on their optimal apparent association and Stern-Volmer constants (K_app and K_SV > 10⁴ M⁻¹). Radical scavenging studies revealed that the metal complexes have high activities towards the neutralization of NO and DPPH radicals. Data attained from the BSA electronic spectrophotometric titrations for the majority of the metal complexes illustrated distinct hyperchromism accompanied with blue shifts which indicates unwinding of the protein strands. Predominately, the metal complexes showed moderate cytotoxicity against both triple-negative breast cancer and cervical cancer cell lines that was greater than that of 5-fluorouracil.

Pre-diabetes is a condition that precedes type 2 diabetes mellitus (T2DM) that is characterised by elevated glycated haemoglobin (HbA1c). The management of pre-diabetes includes the combination of dietary and pharmacological interventions to increase insulin sensitivity. However, poor patient compliance has been reported with regard to dietary interventions, therefore, new alternative drugs are required that can be effective even without the dietary intervention. In our laboratory, we have synthesised a novel ruthenium complex that has been shown to have elevated biological activity. This study investigated the effects of this complex in both the presence and absence of dietary intervention on glucose handling in a diet-induced pre-diabetes rat model. Pre-diabetic animals were randomly assigned to respective treatment groups. The ruthenium complex was administered to pre-diabetic rats once a day every third day for 12 weeks. The administration of the ruthenium complex resulted in reduced fasting blood glucose, food intake, and body weight gain which was associated with decreased plasma ghrelin, insulin, and HbA1c levels in both the presence and absence of dietary intervention. The administration of the ruthenium complex ameliorated glycaemic control and insulin sensitivity in pre-diabetic rats. The results of this study warrant further investigations as this compound could potentially be able to re-sensitize insulin resistant cells and reduce the incidence of T2DM.