目的 合成槲皮素磺酸化衍生物（QSA），并探究其體內外抗腫瘤作用。方法 于槲皮素5'位引入了磺酸基合成QSA；高效液相色譜（HPLC）法測定其溶解度；MTT法檢測QSA和槲皮素（0.1、0.5、1.0、2.5、5.0、10.0、25.0和100.0μg/mL）對4T1、HeLa和HepG2細胞的增殖抑制作用，計算其半數(shù)抑制濃度（IC₅₀）；制備4T1荷瘤小鼠模型，隨機分成6組（每組8只），分別為模型（iv生理鹽水）組，紫杉醇（PTX）注射液（陽性對照，8 mg/kg，iv給藥）組，QSA高、中、低劑量（70、45、20 mg/kg，iv給藥）組，槲皮素（70 mg/kg，ig給藥）組。iv組每2天給藥1次，ig組每天給藥1次，隔天監(jiān)測體質量和腫瘤體積。iv給藥7次后將小鼠處死，稱瘤質量并計算抑瘤率，同時剖取獲取肝和脾，計算肝、脾指數(shù)。結果 合成產物QSA的溶解度是槲皮素的4 261倍；QSA對3種腫瘤細胞的增殖抑制作用明顯，與槲皮素IC₅₀值無顯著性差異，其中對4T1細胞的抑制效果最優(yōu)；體內抑瘤實驗結果顯示，各給藥組與模型組比較，均對小鼠瘤體積增長發(fā)揮顯著抑制作用（P<0.001）；槲皮素（70 mg/kg）組抑瘤率為18.64%， QSA 45 mg/kg組抑瘤率最高，為55.37%，與PTX注射液組（55.03%）無顯著性差異，具備成藥性。各組小鼠體質量、肝脾指數(shù)均無顯著性差異，表明QSA安全性較高。結論 槲皮素經磺酸基修飾后解決了水不溶性，體內抗腫瘤活性顯著改善，為結構相近的黃酮類藥物解決給藥問題提供了新思路。

Objective To synthesize quercetin sulfonic acid (QSA) and study its anti-tumor activities in vitro and vivo. Methods QSA was synthesized from quercetin 5'site by sulfonic group and using HPLC analysis to investigate its solubility. The in vitro anti-tumor activity of quercetin and QSA of 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 25.0 and 100.0 μg/mL were assessed in contrast using MTT assay, and the half inhibitory concentration (IC₅₀) was calculated. The in vivo anti-tumor therapeutic efficacy was investigated using 4T1 tumor bearing mice. The 4T1 tumor-bearing mice were randomly divided into six groups:model group (iv saline), paclitaxel (PTX) injection group (positive control, 8 mg/kg, iv administration), QSA high, medium and low dose (70, 45, 20 mg/kg, iv administration), quercetin (70 mg/kg, ig administration) group. Group IV was administered one times every 2 d, and the Ig group was given one times a day, and the body weight and tumor volume were monitored the next day. The mice were sacrificed after 7 times of iv administration, and the tumor mass was weighed and the tumor inhibition rate was calculated.At the same time, the liver and spleen were obtained and the index of liver and spleen was calculated. Results QSA solubility increased to 4261 times; In vitro, the anti-tumor therapeutic efficacy of QSA has the same inhibitory effect as quercetin, inhibition rate of 4T1 cells was 21.75%; The results of in vivo tumor inhibition test showed that the tumor volume growth of mice was significantly inhibited in each group compared with model group (P<0.001); the tumor inhibition rate of ig quercetin (70 mg/kg) was 18.64%, and that of iv QSA (45 mg/kg) was the highest (55.37%), which had no significant difference with PTX injection group (55.03%). There was no significant difference in body weight and liver and spleen index between each group, indicating that QSA had higher safety. Conclusion QSA solves the problem of water insolubility and significantly improved vivo anti-tumor effect, so it can be used as a model for flavonoids to solve difficulty administration.

國家自然科學基金-廣東聯(lián)合基金資助項目（U1401223）