维甲酸衍生物的合成及其抗肿瘤活性筛选

Synthesis and anti-tumor activity of retinoic acid derivatives

目的:合成新型维甲酸衍生物,并研究其抗肿瘤活性。方法:以全反式维甲酸(ATRA)和三氟甲苯衍生物为原料,采用DCC-DMAP法,合成一系列维甲酸衍生物。药理活性筛选实验考察化合物对白血病细胞株NB4的诱导肿瘤细胞分化活性。结果:通过1H-NMR,13C-NMR和HR-MS确认维甲酸衍生物结构。药理筛选实验表明化合物1D,1E可以显著抑制肿瘤细胞生长,流式细胞仪检测表明化合物1D具有诱导分化能力。结论:维甲酸类衍生物合成方法简单易行,化合物1D能有效的诱导NB4细胞分化。

Objective： To synthesize a series of new retinoic acid derivatives and screen their anti-tumor activity. Methods： These compounds were prepared from all-trans retinoic acid （ATRA） and trifluorophenyl derivatives as starting agents by condensation reaction using dicyclohexylcarbodiimide （DCC） as a condensing reagent and 4-dimethylaminopyridine （DMAP） as a catalyst. The anti-tumor activity was investigated in NB4 cells by MTT and flow cytometric assays. Results： The structures of 7 new compounds were confirmed by spectral analysis including ^1H-NMR, ^13C-NMR and MS. Pharmacological screening test indicated that compounds 1D and 1E markedly inhibited the growth of NBg ceils. Flow cytometric analysis demonstrated that compound 1D induced differentiation of NB4 cells. Conclusion： This readily manipulated process can synthesize a bioactive compound, 1D, which might efficiently induce differentiation of NB4 cells.