崔佳, 熊邵文, 姜雨辰, 黄昕玥, 李丽梅. 娇嫩黄堇生物碱成分及脲酶抑制活性研究J. 药学学报, 2025, 60(10): 3131-3138. DOI: 10.16438/j.0513-4870.2025-0323
引用本文: 崔佳, 熊邵文, 姜雨辰, 黄昕玥, 李丽梅. 娇嫩黄堇生物碱成分及脲酶抑制活性研究J. 药学学报, 2025, 60(10): 3131-3138. DOI: 10.16438/j.0513-4870.2025-0323
CUI Jia, XIONG Shao-wen, JIANG Yu-chen, HUANG Xin-yue, LI Li-mei. Study on the alkaloids of Corydalis delicatula D. G. Long and their urease inhibitory activityJ. Acta Pharmaceutica Sinica, 2025, 60(10): 3131-3138. DOI: 10.16438/j.0513-4870.2025-0323
Citation: CUI Jia, XIONG Shao-wen, JIANG Yu-chen, HUANG Xin-yue, LI Li-mei. Study on the alkaloids of Corydalis delicatula D. G. Long and their urease inhibitory activityJ. Acta Pharmaceutica Sinica, 2025, 60(10): 3131-3138. DOI: 10.16438/j.0513-4870.2025-0323

娇嫩黄堇生物碱成分及脲酶抑制活性研究

Study on the alkaloids of Corydalis delicatula D. G. Long and their urease inhibitory activity

  • 摘要: 采用硅胶、碱性氧化铝、MCI、葡聚糖凝胶Sephadex LH-20柱色谱和高效液相色谱等多种色谱技术, 从娇嫩黄堇(Corydalis delicatula D. G. Long) 总生物碱中分离得到15个生物碱化合物。通过质谱、核磁共振波谱、紫外可见光谱等方法分别鉴定为(-)-tetrahydrocorysamine (1)、corysamine (2)、berberrubine (3)、(-)-scoulerine (4)、bicuculline (5)、(-)-corlumine (6)、scoulerine-β-N-oxide (7)、salutaridine N-oxide (8)、allocryptopine (9)、protopine (10)、coryximine (11)、cryptopine (12)、cis-N-methylstylopine (13)、hunnemannine (14) 和corlicatine A (15)。所有化合物均首次从娇嫩黄堇中分离得到, 其中corlicatine A (15) 为新化合物。药理活性研究表明, 1对洋刀豆脲酶(JBU) 的抑制活性最强, IC50值为1.28 µmol‧L-1, 优于阳性对照物乙酰氧肟酸(AHA)。通过无机试剂对生物碱抑制JBU的影响实验, 发现四个生物碱(161112) 与无机试剂氟化钠(NaF) 及丙烯酸丁酯(BA) 之间存在协同抑制作用。将活性最好的生物碱(1) 与JBU蛋白进行分子对接实验, 未发现与JBU公认的活性中心位点Ni2+发生作用。结合无机试剂对生物碱抑制JBU活性的影响, 推测异喹啉类生物碱对脲酶的抑制作用可能涉及Ni2+以外的其他靶点或机制。

     

    Abstract: Fifteen compounds were successfully isolated from the total alkaloid content of Corydalis delicatula D. G. Long using a variety of chromatographic techniques, including silica gel, basic alumina, MCI, Sephadex LH-20 column chromatography, and HPLC. The structures of the isolated compounds were identified as (-)-tetrahydrocorysamine (1), corysamine (2), berberrubine (3), (-)-scoulerine (4), bicuculline (5), (-)-corlumine (6), scoulerine-β-N-oxide (7), salutaridine N-oxide (8), allocryptopine (9), protopine (10), coryximine (11), cryptopine (12), cis-N-methylstylopine (13), hunnemannine (14), and corlicatine A (15) through spectroscopic methods such as MS, NMR, and UV. These compounds were isolated for the first time from C. delicatula, and corlicatine A (15) is a new compound. Pharmacological testing revealed that compound 1 demonstrated excellent inhibition against Jack bean urease (JBU), with an IC50 value of 1.28 µmol‧L-1, surpassing the effectiveness of the positive control AHA. The synergistic inhibitory influence on JBU activity by compounds 1, 6, 11, 12 and inorganic reagents NaF and BA were proved by addition of competitive inhibitors NaF or BA. The molecular docking experiment between the most active alkaloid (-)-tetrahydrocorysamine (1) and the urease protein of the JBU was not found to interact with Ni2+, which is recognized as the active site of urease. Consequently, considering the impact of inorganic reagents on the inhibitory properties of alkaloids against JBU, it is hypothesized that the inhibitory effect of isoquinoline alkaloids on urease may involve targets or mechanisms other than Ni2+.

     

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