The nitrogen-bearing heterocycle pyridine in its several analogous forms occupies an important position as a precious source of clinically useful agents in the field of medicinal chemistry research.

Diabetes mellitus is an emerging predator and affecting around 422 million adults worldwide. Higher levels of circulating insulin and increased pressure on the pancreas to produce insulin have been inferred as possible etiology for diabetes leading to a higher risk of pancreatic cancer. Out of several drug targets in hypoglycemic discovery, Dipeptidyl peptidase-IV (DPP-IV) has been considered an emerging target. It is a protease enzyme which inactivates incretin hormones i.e., Glucagonlike peptide 1 (GLP-1) and glucose-dependent insulin tropic polypeptide (GIP). Inhibition of DPP-4 results in the longer action of GLP-1 and GIP, therefore, DPP-4 inhibitors play an important role in maintaining glucose homeostasis. In comparison to early oral hypoglycemic, DPP-IV inhibitors are well tolerated and provide a better glycemic control over a longer period. These enzymes are expressed in a dimeric form on the surface of different cells such as prostate, liver and small intestinal epithelium cells. Disruption of the local signaling environment is an emerging factor in cancer development. Till date, not even a single DPP-IV inhibitor as anticancer has been developed. This review focuses on various features of the enzyme and their suitable inhibitors for target disease.

In this article, Ru(II)–arene-2-pyridinylbenzoxazole complexes [(η⁶-p-cymene)RuCl(κ²-N,N-5-bromo-2-(pyridine-2-yl)benzo[d]oxazole)] (4) and [(η⁶-benzene)RuCl(κ²-N,N-5-bromo-2-(pyridine-2-yl)benzo[d]oxazole)] (5) and Ru(II)–arene-2-quinolylbenzoxazole complexes [(η⁶-p-cymene)RuCl(κ²-N,N-5-bromo-2-(quinoline-2-yl)benzo[d]oxazole)] (4′) and [(η⁶-benzene)RuCl(κ²-N,N-5-bromo-2-(quinoline-2-yl)benzo[d]oxazole)] (5′) were synthesized and characterized using various spectroscopic techniques. Structural analysis indicates that the Ru(II) centres are in a distinct mononuclear, one-sided octahedral [RuN₆] coordination geometry with two neutral bidentate nitrogen donors in the bromobenzoxazole ligands. All four complexes exhibit three different electronic bands: a sharp band at 300–330 nm due to ligand-to-ligand charge transfer (LLCT); a band around 400 nm due to metal-to-ligand charge transfer; and a small broad peak at around 600 nm due to ligand-to-metal charge transfer. The fluorescence abilities of the four complexes were studied using the LLCT absorption peak as the excitation energy in dimethylsulfoxide: water (1 : 1, v/v), and the quantum yield was found to decrease in the order of 5′ > 4′ > 4 > 5. Density functional theory calculations reveal that the highest-occupied molecular orbital is primarily located on the benzoxazole ring system, while the lowest-unoccupied molecular orbital is mainly located on the Ru atom, which implies possible charge transfer from ligand to metal. The binding strengths of the Ru(II) complexes with DNA (5′ > 4′ > 4 > 5) and bovine serum albumin (4′ > 5′ > 5 > 4) were on the order of 10⁵–10⁶ and 10³–10⁵ M⁻¹, respectively. The conductometric data reveal that all four complexes are non-electrolytic in nature, and viscosity decreases in the order of 5′ > 4′ > 4 > 5. This might be due to the effective intercalation of 5′ compared to the other complexes. DNA and protein docking studies suggest that all the complexes interact with DNA through the minor groove and favourably occupy the active sites of proteins based on dipole–dipole interactions. Gel electrophoresis studies show that all complexes degrade plasmid DNA (1 kb) completely within 1 h of exposure time. MTT assay results indicate that all complexes exhibit highly selective cytotoxicity for two cancer cell lines (Caco-2 and HeLa) with respect to normal HEK-293 cells. Among the complexes, 4′ and 5 show the highest cytoselectivities for the Caco-2 and HeLa cell lines, respectively.

In recent years, Ru(II) complexes have gained high importance in medicinal chemistry due to their significant anti-cancer activities, which are directly related to their DNA binding ability. In this report, the chemistry and cytotoxicity of two new Ru(II) complexes containing imidazole pyridine (Ru-1) and imidazole quinoline (Ru-2) have been studied. The prepared compounds were characterized using infrared (IR), nuclear magnetic resonance (NMR), mass spectrometry (MS), isothermal titration calorimetry (ITC), UV-Vis, and fluorescence spectral techniques. The structural analyses show that the Ru(II) complexes exhibit a ‘piano stool’ coordination geometry and they are composed of one bound arene, two sigma bonded benzil nitrogen atoms, and labile chlorine linked to Ru(II). The photo-physical properties of these complexes were examined, and they exhibit absorption peaks at 260 nm and 380 nm, which are due to the involvement of intra-ligand charge transitions (ILCT) and metal-to-ligand charge transitions (MLCT), respectively. The binding process of the Ru(II) complexes with DNA and BSA is non-covalent in nature and the binding constants of Ru-1 and Ru-2 complexes with DNA and BSA were found to be 1 × 10⁵ M⁻¹ and 1 × 10³ M⁻¹, respectively. In the presence of the Ru(II) complexes, ethidium bromide (EtBr) is competitively displaced from DNA by intercalation of the Ru(II) complexes in DNA and it is well corroborated by viscosity and in silico studies. Both the ligands and Ru(II) complexes were carefully investigated in vitro for cytotoxicity against HeLa, MCF-7, and MDA-MB-231 cells. Surprisingly, both Ru(II) complexes exhibit superior cytotoxicity to cisplatin with a low LD₅₀ value against the examined cancer cells. Besides, an insignificant effect on HEK normal cells (LD₅₀ > 140 μM) was observed.