New Water‐Soluble N‐Heterocyclic Carbene‐Palladium Complexes as Promising Anti‐Tumor Agents: Investigating DNA and Protein Interactions

Abstract

This investigation focuses on the synthesis and characterization of three new, water-soluble palladium complexes, with potential to overcome the drawbacks of platinum-based anti-cancer drugs. The complexes contain small N-heterocyclic carbene (NHC) ligands, having groups that impart water solubility. The anti-cancer effects of these complexes were evaluated in two different cancer cell lines, namely,HeLa, a cervical cancer cell line and A549,adenocarcinoma human alveolar basal epithelial cell line. Cytotoxicity of the complexes was compared with cisplatin, an established platinum-based anti-cancer moiety, using the MTT assay (MTT is 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide). Aqueous solutions of the synthesized complexes demonstrated significant cytotoxicity in both the cell lines. The synthesized metal complexes resulted in a stronger, cytotoxic effect in A549 cells (lung cancer cells), as compared to cisplatin. Furthermore, interaction of these palladium compounds with DNA was studied using gel electrophoresis and spectrometry methods. The result suggested that the complexes interacted with DNA via intercalation. Interaction with BSA (Bovine Serum Albumin) was investigated using UV-Vis spectroscopy suggesting positive interaction of palladium complex with BSA proteins. Furthermore, fluorescence studies revealed quenching of protein fluorescence thus, indicating dynamic quenching mechanism with the number of association sites being calculated as~1.

New heterobimetallic ferrocenyl derivatives are promising antitrypanosomal agents

“…77 The determined binding constant was K bc = 6.110 3 M 1 , which is somewhat lower than those reported for other metal complexes that interact reversibly with this protein (K bc in the order of 10 5 M 1 ). [77][78][79] So, the obtained K bc value is within a nearly optimal range: it is high enough for the compounds to bind albumin to be transported but, nevertheless it is sufficiently low to let the compound be released from albumin upon arrival to the target. 80 The n value obtained was approximately equal to 1 suggesting the existence of a single binding site type between BSA and the M-dppf-L3 complex.…”

Discovery, Synthesis, and Scale-up of Efficient Palladium Catalysts Useful for the Modification of Nucleosides and Heteroarenes

“…In a similar vein, our group also developed water-soluble NHC ligands and their Pd-based complexes. We used this to catalyze the Suzuki-Miyaura coupling in water and tested the anticancer activities of the products [56]. The introduction of sulfonate functionality in the NHC ligand was achieved by the ring opening of a cyclic sultone derivative by an amine or nucleophilic nitrogen atoms.…”