硝基呋喃乙烯喹啉((E)-2-(2-(5-nitrofuran-2-yl)vinyl)quinolin-8-ol)對於難消融時期前列腺癌具有很強的抑制效果,但對正常細胞毒性過強,因此有實用時的障礙,本研究主要將HZY-2023中喹啉和芳香環或雜環的連接部分由單烯鍵變成雙烯鍵,並改變不同芳香環上的取代基,藉由此方法改變其氧化還原性質而達到有效的抑制效果,並降低其對正常細胞毒性;結果其衍生物對於雄激素非依賴性前列腺癌有選擇性的抑制效果,且降低對正常細胞的毒性。另一方面針對合成雙烯類化合物的合成路徑做了一系列的優化,新路徑可以降低所需成本且純化容易並可減少許多時間來得到目標的化合物。
(E)-2-(2-(5-nitrofuran-2-yl)vinyl)quinolin-8-ol (HZY-2023) has demonstrated a strong inhibitory effect on difficult ablation period of prostate cancer cells. However, its cytotoxity against normal cells prevents further application. In this study, the alkene between two aromatic rings was replaced by diene to alter the redox properties. This modification improve inhibitory effect and reduced the normal toxiaty aginst cell. The results of biological assay indicated series of derivatives which exhibit selectively cytotoxity against androgen-independent and reduce toxicity on normal cells. Meanwhile, optimization of synthetic conditions focuses on cost efficiency, easy purification and efficiency improvement to afford the target compounds.