Synthesis and biological evaluation of arginyl–diosgenin conjugate as a potential bone tissue engineering agent

Water‐soluble arginyl–diosgenin (Arg‐DG) conjugate was designed, synthesized, and evaluated for a biological activity. The Arg‐DG conjugate was characterized using FT‐IR, 1H NMR, 13C NMR, and HPLC‐MS analyses, followed by a biological activity evaluation. Compared with DG, the Arg‐DG conjugate showed a decreased cytotoxicity against L929 cells and an increased antiproliferative activity against hepatocellular cells. The safety of the Arg‐DG conjugate was confirmed using the highly sensitive Alamar Blue assay, which indicated that it increased the cellular metabolic activity at suitable concentrations. The Arg‐DG conjugate promoted an endothelial tube formation as well. Furthermore, the Arg‐DG conjugate improved the bone morphogenetic protein 2 (BMP2)‐induced osteoblastic differentiation with synergistic effects on alkaline phosphatase (ALP) activity and mineralization. These results suggest that the Arg‐DG conjugate developed in this study has great potentials for biomedical applications such as bone tissue engineering. Arginyl–diosgenin (Arg‐DG) conjugate was successfully synthesized and characterized to increase solubility of poorly water‐soluble diosgenin (DG). Arg‐DG conjugate was manifested to reduce the cytotoxicity of DG against normal cells and increase the cellular metabolic activity of normal cells in vitro, while enhancing the antiproliferative activity against HepG2 cell. Arg‐DG conjugate was demonstrated to promote endothelial tube formation and BMP2‐induced osteogenesis potentially resulting in synergistically stimulating alkaline phosphatase activity and mineralization.