Preparation of novel anthraquinone-based aspirin derivatives with anti-cancer activity

Gastric cancer is one of the most common and deadly cancers among men and women and is the third leading cause of cancer mortality worldwide. Thus, discovering and developing novel therapeutics for gastric cancer has become a global priority. In this study, we synthesized two novel anthraquinone-based aspirin derivatives, Asp-X₃ and Asp-X₃-CH₃, with therapeutic potential for gastric cancer. The structures of the two compounds were determined by 1D, 2D-NMR, and High-Resolution Mass (HRSM). Asp-X₃ and Asp-X₃-CH₃ could inhibit the growth of gastric cancer cells (SGC7901), yielding IC₅₀ values 10-fold lower than that of Aspirin. Asp-X₃ and Asp-X₃-CH₃ were less toxic to gastric mucosal cells, yielding IC₅₀ values that were about 2-fold higher than the corresponding IC₅₀ values determined with SGC7901 cells. Asp-X₃-CH₃ and Asp-X₃ also induced SGC7901 cells to undergo apoptosis, yielding apoptotic rates that were about twice the rate induced by Aspirin. Asp-X₃-CH₃ did not cause significant loss of COX-1 expression in gastric mucosal cells, whereas Asp-X₃ and Aspirin both caused significant loss of COX-1 expression as demonstrated by Western blot, consistent with their effects on the content of PGE₂ in these cells as determined by ELISA assay. However, both Asp-X₃-CH₃ and Asp-X₃ exerted a similar effect on the level of COX-2 in gastric cancer cells, causing as much as 90% and 95% reduction in COX-2 expression, respectively. Taken together, the results suggested that Asp-X₃-CH₃ and Asp-X₃ were potentially better agents than Aspirin for the inhibition of gastric cancer cell growth, but Asp-X₃-CH₃ was more effective.