3个芒果苷酰化衍生物的化学合成及抗炎作用研究

Synthesis and Anti-inflammatory Activity of Mangiferin Acylated-derivatives

摘要:

目的: 将芒果苷分子上的一部分羟基进行酰化衍生,以提高化合物的脂溶性;然后比较芒果苷及其酰化衍生物的抗炎活性。 方法: 将芒果苷分别与乙酸酐、丙酸酐和丁酸酐反应,反应产物用硅胶柱层析分离出化合物单体,用波谱解析化合物的化学结构。雄性小鼠随机分为空白对照组,地塞米松阳性药组(0.115 mmol·kg^-1),芒果苷高、中、低剂量组(1.0,0.5,0.25 mmol·kg^-1)和酰化衍生物 各高、中、低剂量组(0.25,0.125,0.063 mmol·kg^-1),每组10只。各组连续经口给药5 d。末次给药45 min后,尾静脉注射伊文思蓝,右耳滴二甲苯致炎,腹腔注射冰醋酸。15 min后处死小鼠,用打孔器沿左、右耳廓相同部位打下两侧耳片,分别称重,计算耳廓肿胀度;另用生理盐水腹腔注射进行清洗,收集腹腔液测定吸光度(A),用以评价腹腔毛细血管通透性。 结果: 得到3个新结构化合物: (a) 7,2',3',4',6'-五乙酰化芒果苷衍生物(PAM), (b) 3,6,7,2',3',4',6'-七丙酰化芒果苷衍生物(HPM)和 (c) 3,6,7,2',3',4'-六丁酰化芒果苷衍生物(HBM)。与空白对照组比较,芒果苷高、中剂量组、PAM高、中剂量组、HPM高、中、低剂量组和HBM高、中、低剂量组均能显著抑制小鼠耳廓肿胀(P<0.05),并能显著抑制毛细血管的通透性,减少腹腔液渗出(P<0.01或P<0.05),显示出显著的抗炎作用,并呈现一定的结构-效应关系。 结论: PAM,HPM和HBM为首次报道的新结构化合物;芒果苷酰化衍生物只需相当于芒果苷1/4的摩尔剂量,即可显示出与芒果苷相似的抗炎作用,说明其抗炎作用的效价强度高于芒果苷,提示其抗炎活性比芒果苷强。

Abstract:

Objective:To prepare acylated derivatives of mangiferin, and then to evaluate their anti-inflammatory activity. Method: Mangiferin was respectively reacted with acetic anhydride, propionic anhydride and butyric anhydride to produce acylated-derivatives. Swelling of mice ear and permeability of mice celiac capillary were used to evaluate the anti-inflammatory activity. Result: 3 compounds were confirmed: (a) 7,2',3',4',6'-penta-acetyl-mangiferin(PAM), (b) 3,6,7,2',3',4',6'-hepta-propionyl-mangiferin(HPM), (c) 3,6,7,2',3',4'-hexa-butyryl-mangiferin(HBM). Mangiferin's high and medium dose group (1.0, 0.5 mmol·kg^-1), PAM's high and medium dose group (0.25, 0.125 mmol·kg^-1), HPM's high, medium and low dose group (0.25, 0.125, 0.063 mmol·kg^-1) and HBM's high, medium and low dose group (0.25, 0.125, 0.063 mmol·kg^-1) could significantly inhibit the ear swelling and permeability of celiac capillary in mice, showing obvious anti-inflammatory effect. Conclusion: PAM, HPM and HBM were novel compounds and were reported for the first time.Acylated derivatives have stronger anti-inflammatory activity than their parent compound mangiferin.