Design and synthesis of cyclotriphosphazene derivatives bearing hydroxyflavone groups: Antioxidant properties and cytotoxic effects in breast cancer cells

Cancer is still a major global health issue and one of the deadliest diseases affecting human health today. The synthesis of different flavone derivatives has attracted significant attention in cancer research due to the potential of this group of compounds as anticancer agents. For this purpose, flavone derivative monospirocyclophosphazene compounds (9-11) have been synthesized and characterized by MALDI-TOF MS, 1H, 13C, 31P, COSY NMR and FT-IR spectroscopy. In addition, the solid-state structure and geometry of compound 10 were determined using single-crystal X-ray structural analysis. The antioxidant potential of the compounds was evaluated through DPPH radical scavenging assays, in comparison with well-known standards such as BHA, BHT, and Trolox. Among the synthesized compounds, compound 9 exhibited the highest antioxidant activity with a DPPH scavenging rate of 94.51 %, followed by compound 10 with 92.15 % and compound 11 with 88.96 %, demonstrating notable and selective antioxidant properties. The cytotoxicity results of the compounds 9, 10, and 11 in MCF-7 (human breast cancer) cells, assessed using the MTT method, showed viability percentages of 58.28 %, 41.34 %, and 41.88 %, respectively (IC50: 5.288, 10.170, and 10.870), providing meaningful and effective data for cytotoxicity activities. Low toxicity of the compounds was detected on MCF-12A normal breast epithelial cells. The antioxidant activity of the synthesized cyclotriphosphazene derivatives was evaluated alongside their anticancer effects to explore their potential dual role in modulating oxidative stress and contributing to selective cytotoxicity in cancer cells. Overall, these findings suggest that the synthesized flavone-based monospirocyclophosphazene compounds possess promising antioxidant and anticancer properties, making them potential candidates for further development as selective anticancer agents that spare healthy cells.