Synthesis, structural and thermal properties of the hexapyrrolidinocyclotriphosphazenes-based protic molten salts: Antiproliferative effects against HT29, HeLa, and C6 cancer cell lines

Novel three protic ionic liquids or protic molten salts (PILs) (la, Ib, and Ic) were obtained from the reactions of hexapyrrolidinocyclotriphosphazenes, [N3P3(NC4H8)(6)] PYR (1), with the gentisic (2,5-dihydroxy benzoic), decanoic and boric acids. The structures of PILs were determined by elemental analyses, FTIR and H-1,C-13{H-1}, P-31{H-1} NMR techniques. The thermal properties of PYR (1) and PILs were described using thermogravimetric analysis (TGA). The results obtained from TGA indicate that the onset temperatures of PYR (1), la, lb, and Ic are 303.38, 256.82, 166.81, and 287.35 degrees C, respectively. Binding interaction of these protic ionic liquids with calf thymus (CT-DNA) and bovine serum albumin (BSA) were evaluated by UV-vis spectrophotometry, fluorescence spectroscopy techniques, and electrophoresis measurements. Biological properties of the compounds were evaluated by using in vitro techniques towards three cancer cell lines (HT29, HeLa, and C6) and one non-cancer cell line, namely Vero. The IC50 data exhibitions that lb and is are the most effective antiproliferative agents against HT29, C6 cells and HeLa cells, respectively. The cytotoxic effects of the compounds were detected to be in a safe level at 75 or 100 g/mL. The analysis of the DNA topoisomerase I relaxing activity indicates that la and lb inhibit topoisomerase I which regulate topological states of DNA strands during the cell process. The apoptotic potential of the compounds at the single cell level indicates that they may inhibit cell proliferation by inducing apoptosis. Immunohistochemistry staining analysis displays that these compounds significantly decreases the level of Bcl-2 in HeLa and HT29 cells while increasing the accumulation of P53. Overall, the potent antiproliferative action, low cytotoxic effect, good solubility in a physiological medium and micro molar range dosage of these compounds reveals that they are likely to be the good drug candidates for pharmacological trials. (C) 2017 Elsevier B.V. All rights reserved.