5-氟尿嘧啶—烟酰胺共晶的制备及其抗肿瘤活性研究

摘要

Objective:To synthesize 5-fluorouracil-nicotinamide (5-FU-NCT) cocrystal and to investigate its physicochemical and biological properties.Methods:The cocrystal of 5-Fu-NCT was prepared through the cooling technology.PXRD,NMR,FTIR and DSC were used to characterize the structure of 5-FU-NCT cocrystal.Solubility was measured by HPLC method.Drug resistant human liver cancer BEL-7402/5-FU cells were treated with 5-FU-NCT cocrystal,the inhibition effect was tested by MTT and HE staining,and cancer cell migration was determined by scratch test.Results:According to PXRD,NMR,FTIR and DSC results,the cocrystal of 5-Fu-NCT had been synthesized successfully.The characteristic diffraction peaks (2θ/°) of the cocrystal were 16.4,20.4,22.3,27.9 and 30.1.The solubility of 5-FU-NCT was 13.5 g/L as measured by HPLC.The antitumor activity tests showed that 5-FU-NCT cocrystal enhanced anticancer effect of 5-FU,and the IC50 of 5-FU and 5-FU-NCT was 129.6 μg/mL and 42.6 μg/mL,respectively.Conclusion:5-Fu-NCT cocrystal have been synthesized successfully through the cooling technology and it shows a more enhanced anticancer effect in comparison to 5-FU on BEL-7402/5-FU cells.%目的:以烟酰胺(NCT)为共晶形成物制备5-氟尿嘧啶—烟酰胺共晶(5-Fu-NCT),对其理化特性和生物学性质进行研究.方法:采用冷却结晶法制备5-Fu-NCT共晶,用X射线粉末衍射法、核磁共振、红外光谱、差示扫描量热法等方法对其结构进行表征,用高效液相色谱法测定其溶解度,用MTT法、HE染色和细胞划痕实验测定其对肿瘤细胞活性的影响.结果:成功制备了5-FU-NCT,其特征衍射峰(2θ)为16.4、20.4、22.3、27.9、30.1°.共晶溶解度为13.5 g/L.体外细胞试验结果表明,5-Fu和5-Fu-NCT作用于BEL-7402/5-Fu细胞的半数致死浓度值(IC50值)分别是129.6 μg/mL、42.6 μg/mL;细胞划痕实验、HE染色结果表明,5-Fu-NCT对耐5-Fu的BEL-7402/5-Fu细胞毒性更强.结论:采用冷却结晶法成功制备了5-Fu-NCT.相比5-Fu,5-Fu-NCT对耐Fu肿瘤细胞有更强的抗肿瘤活性.