Ru(II)-based complexes with N-(acyl)-N′,N′-(disubstituted)thiourea ligands: Synthesis, characterization, BSA- and DNA-binding studies of new cytotoxic agents against lung and prostate tumour cells

• Ru(II) complexes with N-(acyl)-N′,N′-(disubstituted)thioureas.
• The compounds interact with DNA and BSA by electrostatic interactions.
• Promising agents against prostate (DU-145) and lung (A549) tumour cells.
• High cytotoxic activity against tumour cells than cisplatin.

Four ruthenium(II)-based complexes with N-(acyl)-N′,N′-(disubstituted)thiourea derivatives (Th) were obtained. The compounds, with the general formula trans-[Ru(PPh3)2(Th)(bipy)]PF6, interact with bovine serum albumin (BSA) and DNA. BSA-binding constants, which were in the range of 3.3–6.5 × 104 M− 1, and the thermodynamic parameters (ΔG, ΔH and ΔS), suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. Also, binding constant by spectrophotometric DNA titration (Kb = 0.8–1.8 × 104 M− 1) and viscosity studies indicate weak interactions between the complexes and DNA. Cytotoxicity assays against DU-145 (prostate cancer) and A549 (lung cancer) tumour cells revealed that the complexes are more active in tumour cells than in normal (L929) cells, and that they present high cytotoxicity (low IC50 values) compared with the reference metallodrug, cisplatin.

The first examples of complexes of Ru(II) containing N-(acyl)-N′,N′-(disubstituted)thioureas were synthesized and characterized. The complexes interact with DNA and BSA mainly by weak electrostatic interactions and they are very active against prostate (DU-145) and lung (A549) tumour cells, and thus are promising anticancer candidates.Figure optionsDownload as PowerPoint slide