Glycoconjugate Pd(ii) and Cu(ii) complexes of fluorinated N,O Schiff base ligands for targeted cancer therapy: synthesis, characterization and in vitro cytotoxic activity evaluation

Abstract

In the present investigation, we engineered a series of Pd(II) and Cu(II) metal complexes bearing N-aryl fluorinated O-glycoconjugate Schiff base ligands as potential anticancer agents. These novel metal complexes, incorporating CF₃ and α-D-glucose groups, were designed, synthesized, and thoroughly characterized using multinuclear NMR, ATR-FTIR spectroscopy, electron paramagnetic resonance (EPR), mass spectrometry, elemental analysis, and single-crystal X-ray diffraction for select compounds. Their effects were subsequently evaluated on six cancer cell lines: human Caucasian prostate adenocarcinoma (PC-3), mammary adenocarcinoma (MCF-7), human colorectal adenocarcinoma (HCT-15), human lung adenocarcinoma (SK-LU-1), myelogenous leukemia (K-562), and human malignant glioblastoma (U-251). Notably, compound Pd(L¹G)₂ exhibited the highest cytotoxicity against the various cancer cell lines while demonstrating reduced activity against non-cancerous cells. This finding underscores the potential of carbohydrate moieties to enhance selectivity towards malignant cells. Additionally, in silico molecular docking studies were conducted to evaluate interactions between the copper and palladium complexes, revealing binding patterns of the newly synthesized compounds. This analysis indicated that Pd(II) complexes with glycosylated ligands exhibit a stronger DNA binding affinity. Generally, the glycosylated ligands enhance hydrogen bonding interactions, resulting in more stable and effective binding.