零余子中环肽类化学成分及其生物活性研究

Cyclopeptides Chemical Constituents of bulbils of Dioscorea opposita Thunb.and Their Bioactivities

目的探究零余子(bulbils of Dioscorea opposita Thunb.)中含氮类化学成分及其生物活性。方法采用硅胶、Sephadex LH-20、MCI gel CHP-20、ODS等柱色谱及制备型高效液相分离纯化,结合理化性质及其波谱数据鉴定化合物结构。采用多柔比星诱导的NRK-52E细胞损伤模型及皮质酮诱导的PC-12细胞损伤模型分别检测所得化合物的肾细胞保护作用及神经细胞保护作用。结果从零余子中分离得到15个含氮类化合物,分别鉴定为环(L-苯丙-L-酪)二肽(1)、环(L-缬-L-脯)二肽(2)、环(D-色-D-酪)二肽(3)、环(L-脯-L-酪)二肽(4)、环(L-苯丙-L-丙)二肽(5)、环(L-亮-L-脯)二肽(6)、环(L-异亮-L-脯)二肽(7)、环(D-脯-L-酪)二肽(8)、环(L-苯丙-L-脯)四肽(9)、3-羟基-3-(2-丙酰)-2,4(1H,3H)-喹啉二酮(10)、3-吲哚甲醛(11)、木瓜新碱A(12)、1-核糖醇基-2,3-二酮-1,2,3,4-四氢-6,7-二甲基-喹喔啉(13)、白曼陀罗酰胺(14)、苯丙氨酸(15)。化合物2、5、9、14能显著提高NRK-52E细胞活力。化合物对PC-12细胞活力均无明显影响。结论化合物2~5、7~9、11~14均为首次从薯蓣属植物中分离得到。首次报道化合物2、5、9、14在体外中表现出较好的肾细胞保护作用。

OBJECTIVE To explore the constituents from the bulbils of Dioscorea opposita Thunb.and their biological activities.METHODS The compounds were separated and purified by various chromatography methods.Their structures were elucidated on the basis of physicochemical properties and spectroscopic data.The protective effects of the compounds on renal cells and nerve cells were detected by adriamycin-induced NRK-52 E and corticosterone-induced PC-12 cell injury model respectively.RESULTS Fifteen compounds were isolated and identified as cyclo-(L-Phe-L-Tyr)(1),cyclo-(L-Val-L-Pro)(2),cyclo-(D-Trp-D-Tyr)(3),cylco-(L-Pro-L-Tyr)(4),cyclo-(L-Phe-L-Ala)(5),cyclo-(L-Leu-L-Pro)(6),cyclo-(L-Ile-L-Pro)(7),cyclo-(D-Pro-L-Tyr)(8),cyclo-(L-Phe-L-Pro)(9),3-hydroxy-3-(2-oxopropyl)-2,4(1H,3H)-quinolinedione(10),3-indolcarbaldehyde(11),chaenomeles alkaloid A(12),1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethyl-quinoxaline(13),baimantuoluoamide B(14),and phenylalanine(15).Compounds 2,5,9 and 14 significantly increased the activity of NRK-52 E cells.CONCLUSION Compounds 2-5,7-9,and 11-14 are isolated from this genus for the first time.It is reported for the first time that compounds 2,5,9 and 14 show good renal cell protection effect in adriamycin-induced injury model.