Exploring the binding properties of DNA/BSA and cytotoxicity studies with new terpyridine-ester-based metal complexes (M = Fe(III), Ni(II), Cu(II) and Ru(III)) – A comparative analysis

• Published in: International journal of biological macromolecules 2024-08, Vol.274 (Pt 1), p.132792, Article 132792
• Main Authors: Pandya, Chayan, Sivaramakrishna, Akella
• Format: Article
• Language: English
• Subjects: Apoptosis; Coordination behavior; Cytotoxicity; DFT and docking studies; DNA/BSA binding; IC50; Structural aspects; Terpyridine-esters
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.132792

Many terpyridines and their metal complexes are known to exhibit remarkable potential for the interaction of biological targets. Notably, a subtle change in the structure of the ligand can influence these interactions significantly. In this regard, it would be very interesting to assess the binding affinity of functionalized molecules with DNA/BSA. In this work, a novel ester-based terpyridine (L) and the corresponding four metal complexes with Ni(II) (MC1), Cu(II) (MC2), Fe(III) (MC3) and Ru(III) (MC4) were prepared and structurally characterized using various spectroscopic and analytical techniques including the validation of molecular structures of ligand (L) and Ni(II)-Tpy complex (MC1). The EPR data demonstrate that MC1 is diamagnetic and other complexes (MC2-MC4) exhibit paramagnetic behavior. Additionally, the structures of ligands and metal complexes were determined using DFT studies and the same were utilized for the docking studies. Interestingly, MC3 and MC4 exhibit a predominant lowest binding energy of −9.62 Kcal/mol (with DNA) and −10.05 Kcal/mol (with BSA) respectively. The binding affinity of the ligand and its complexes with protein and DNA was evaluated by spectroscopic techniques. Notably, the cytotoxicity studies of L and MC1-MC4 were performed against the MCF-7 (human breast cancer) cell lines. The complex MC4 displayed great activity with an IC50 of 3.5 ± 1.75 μM among all synthesized compounds and comparable with cisplatin.