Synthesis, characterization and cytotoxic activity studies on cancer cell lines of new paraben-decorated monospiro-cyclotriphosphazenes

Abstract

Cancer is one of the leading causes of death worldwide. Among the causes of cancer-related deaths in women, breast cancer, which is the most common type of cancer in women, is in second place. On the other hand, colon cancer has the highest mortality rate and the fourth highest incidence in the world. For this reason, it is invaluable to find anti-cancer agents for cancer treatment, with research rapidly ongoing. Studies of phosphazene compounds in this field have an important place. For this purpose, monospiro-cyclotriphosphazene compounds decorated with different parabens that likely show biological activity were designed and successfully synthesized for the first time. The structures of the purified compounds (1–6) were elucidated using different spectroscopic techniques, such as matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, Fourier-transform infrared (FT-IR) spectroscopy, and ¹H, ¹³C and ³¹P nuclear magnetic resonance (NMR) spectroscopies. In addition, the solid-state structure and geometry of compound 2 was determined via single-crystal X-ray structural analysis. Then, different concentrations of all of the compounds were investigated to determine their in vitro cytotoxicity activities against human breast adenocarcinoma (MCF-7) and Dukes’ Type C colorectal adenocarcinoma (DLD-1) cell lines by MTT assay. The obtained data were evaluated using Anova analysis methods and are presented as IC₅₀ values. All compounds studied in the 12.5–200 μM concentration range on MCF-7 and DLD-1 cell lines showed cytotoxic effects. The results show that in particular compounds 2 (methyl paraben decorated monospiro-2,2′-biphenoxy cyclotriphosphazene) and 6 (benzyl paraben decorated monospiro-2,2′-biphenoxy cyclotriphosphazene) were generally found to be the most active compounds compared to others in terms of the viability of cells.