Synthesis of curcumin derivatives for suppression of castration-resistant prostate cancer

Abstract

In this work, 20 curcumin derivatives containing halogen atoms or nitrogen atoms were synthesized for suppression of castration-resistant prostate cancer. These curcumin derivatives were prepared by aldol condensation between the substituted benzaldehydes and acetylacetone or ethyl 3-acetyl-4-oxopentanoate. All synthesized compounds were characterized by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, high resolution mass, ultraviolet–visible spectroscopy, fluorescence spectroscopy, and high-performance liquid chromatography. The in vitro cytotoxicity of the prepared compounds against 22Rv1 cells was evaluated by the standard MTT assay. The compounds with good inhibitory activity against 22Rv1 cells were further tested for androgen receptor suppression effect. The results show that all compounds were successfully prepared and the purities are all over 90%. Among all synthesized compounds, compound p and s exhibit better inhibitory activity against 22Rv1 cells as compared to dimethylcurcumin, compound q and r display similar inhibitory activity against 22Rv1 cells as compared to dimethylcurcumin. Compounds p-s also demonstrate enhanced androgen receptor suppression effect against 22Rv1 cells as compared to dimethylcurcumin. This work indicates that compounds p-s show promising inhibitory activity against castration-resistant prostate cancer cells by suppression of androgen receptor.