Acetylated monosaccharide functionalized co-ligand based strong anticancer Pt(II) complexes: Synthesis characterization and biological analyses

Abstract

In this study, we modified ONS-donor tridentate salicylaldimine main ligand-based Pt(II) complexes with monosaccharide functionalized pyridine co-ligand. All these complexes (C1-C12) were prepared in two steps continuous reaction by firstly, abstracting the ancillary chloride of the starting complexes with AgBF₄ and secondly, adding the acetylated β-d-glucose conjugated pyridine. All these complexes were analyzed for their in vitro anticancer potency in human's gastric cancer MKN 45, colon cancer RPMI 4788 and non-small cell lung cancer A549 cells. C9 and C12 were the most potent complexes, these complexes were further studied in cisplatin-resistant human non-small cell lung cancer A549/DDP cells and human normal cells gastric epithelial GES and colonic epithelial NCM 460 cells. The anticancer effects were superior in cisplatin-resistant cells and lower in human normal cells. To show the effect of sugar on the physiological behavior of selected complexes (C9 and C12) and control (oxaliplatin), GLUT1 inhibitor (quercetin)-dependent experiments were performed in cancer cells that revealed lower cancer cells death after GLUT1 inhibitor was added in the presence of C9 and C12, indicated that these complexes exhibited GLUT1-dependent anticancer activity while the presence of GLUT1 inhibitor did not affect the cytotoxicity of oxaliplatin used as a control. Cell morphological study using bright field images or hoechst 33342 staining and flow cytometry analyses were conducted to further confirm the strong apoptotic effect of these complexes. Western blot analyses were performed that revealed mechanistically these complexes induced PARP, caspase 3 and BCL-2 and thereby caused cancer cell death.