异维A酸EP杂质D是异维A酸合成过程中产生产生的杂质,又名阿利维甲酸,是治疗皮肤病领域的重要药物,是全反式维甲酸(式II,化学名:3,7-二甲基-9-(2,6,6-三甲基环己烯-1-基)-2E,4E,6E,8E-全反式壬四烯酸)的9-顺异构体。
异维A酸EP杂质D(式I化合物)的制备:在氮气保护下,往反应瓶中加入乙醇2L、全反式维甲酸100g,搅拌,然后升温至50~55℃,加入PdCl289mg。反应1.5h后,经HPLC检测产物纯度为21%。反应液缓慢降温至0~5℃,保温180分钟,抽滤;滤液加入另一干净反应瓶中,继续降温至-10~-6℃,保温20分钟,抽滤,得到产物异维A酸EP杂质D 12.1g,总收率12.1%,HPLC纯度99.60%。以全反式维甲酸为原料,采用钯化合物催化,在普通的工业级有机溶剂中可得到阿利维甲酸。方法操作简便,成本低,条件可控,便于工业生产;经过后处理步骤后,可得到纯度99%以上的阿利维甲酸,产物收率达到12%以上,具有较高的应用价值。
9-cis-Retinoic acid (1-10 μM; 0-5 days; CA 9-22 and NA cells) treatment significantly decreases proliferation in a dose-dependent manner in CA 9-22 and NA cells. 9-cis-Retinoic acid (1 μM; 24 hours) treatment significantly increases PPARγ functional activity by >200% in CA 9-22 and NA aerodigestive cells. 9-cis-Retinoic acid treatment results in the formation of a nuclear PPARγ-RXRα heterodimer supershift complex in CA 9-22 cells. 9-cis-Retinoic acid inhibits proliferation and induces apoptosis in cutaneous T-cell lymphoma (CTCL) in a dose-dependent and time-dependent manner. 9-cis-Retinoic acid also induces G0/G1 cell cycle arrest by downregulation of cyclin D1. 9-cis-Retinoic acid significantly decreases phosphorylation of JAK1, STAT3, and STAT5 and downregulated Bcl-xL and cyclin D1.
Cell Proliferation Assay
9-cis-Retinoic acid (1 mg/kg; intravenous injection; daily; for 10 days; male C57BL/6J mice) treatment significantly decreases the serum ALT and AST level, alleviates hepatic necrosis of the bile duct ligation (BDL)-mice.