Elgoud Said Asmaa Abo, Afifi Ahmed H, Ali Taha F S, Samy Mamdouh Nabil, Abdelmohsen Usama Ramadan, Fouad Mostafa A, Attia Eman Zekry
Department of Pharmacognosy, Faculty of Pharmacy, Minia University 61519 Minia Egypt
Department of Pharmacognosy, Division of Pharmaceutical Industries, National Research Center Dokki 12622 Giza Egypt.
RSC Adv. 2021 Oct 6;11(52):32740-32749. doi: 10.1039/d1ra06139a. eCollection 2021 Oct 4.
Chemical investigation of roots extract, using chromatographic and spectroscopic techniques, resulted in isolation and identification of eight known compounds. The basic ethyl acetate fraction (alkaloidal fraction) afforded -methylsceletenone, epinine, 4-methoxy phenethylamine, and -methyl tyramine while, the acidic ethyl acetate fraction (non-alkaloidal fraction) afforded only -coumaroyl tyramine. Moreover, the petroleum ether fraction afforded capric acid, tricosanol, and a mixture of β-sitosterol & stigma sterol. Upon screening of anti HCV activity of these three fractions, only the basic ethyl acetate fraction had high activity against HCV with an IC value equal to 2.4 μg mL which provoked us to carry out structure based virtual screening on the drug targets of HCV of isolated alkaloidal compounds as well as the previously dereplicated alkaloids through metabolomics from the antiviral active fraction. The tortuosamine compound exhibited the strongest binding to the active site of NS3/4A helicase with a binding affinity (-7.1 kcal mol) which is very close to the native ligand (-7.7 kcal mol).
采用色谱和光谱技术对根提取物进行化学研究，分离并鉴定出8种已知化合物。碱性乙酸乙酯馏分（生物碱馏分）得到了β-甲基司可林酮、表小檗碱、4-甲氧基苯乙胺和β-甲基酪胺，而酸性乙酸乙酯馏分（非生物碱馏分）仅得到了对香豆酰酪胺。此外，石油醚馏分得到了癸酸、二十三醇以及β-谷甾醇和豆甾醇的混合物。在对这三个馏分的抗丙型肝炎病毒（HCV）活性进行筛选时，只有碱性乙酸乙酯馏分对HCV具有高活性，其半数抑制浓度（IC）值等于2.4 μg/mL，这促使我们对分离得到的生物碱化合物以及先前通过代谢组学从抗病毒活性馏分中去除重复结构的生物碱的HCV药物靶点进行基于结构的虚拟筛选。扭体胺化合物与NS3/4A解旋酶的活性位点表现出最强的结合，结合亲和力为-7.1 kcal/mol，这与天然配体的结合亲和力（-7.7 kcal/mol）非常接近。
