In vitro Antiplasmodial Activities of Alkaloids Isolated from Roots of Worsleya procera (Lem.) Traub (Amaryllidaceae)

A combined phytochemical, crystallographic and biological study of Worsleya procera roots was performed. Fifteen alkaloids were identified by gas chromatography mass spectrometry (GC-MS) and seven of them were isolated. The structures of the alkaloids were elucidated by spectroscopic methods, and a detailed crystallographic study of tazettine was carried out. The isolated alkaloids and the obtained extracts were tested in vitro against Plasmodium falciparum (3D7 and K1 strains) and human hepatocarcinoma cells (HepG2) to assess their antiplasmodial and cytotoxic effects, respectively. One of the isolated alkaloid derivatives, lycorine, exhibited antiplasmodial activity against both sensitive (3D7) and resistant (K1) parasite strains in the low micromolar range (half-maximal sample inhibitory concentration (IC50) values of 2.5 and 3.1 µM, respectively) and displayed a low cytotoxicity profile, with a selectivity index greater than 100. Our findings indicate that lycorine is a hit for antimalarial drug discovery.

本研究对Worsleya procera的根部开展了植物化学、晶体学与生物学的联合探究。通过气相色谱-质谱联用法（GC-MS）共鉴定出15种生物碱，并分离得到其中7种。研究人员采用光谱法解析了所有生物碱的结构，并对他卓新碱（tazettine）开展了详尽的晶体学研究。将分离得到的生物碱及所得提取物进行体外实验，分别针对恶性疟原虫（Plasmodium falciparum，3D7与K1株）以及人肝癌细胞（HepG2）开展测试，以评估其抗疟活性与细胞毒性。其中分离得到的生物碱衍生物石蒜碱（lycorine）对敏感株（3D7）与耐药株（K1）的疟原虫均展现出低微摩尔级的抗疟活性，其半数最大样本抑制浓度（IC50）分别为2.5 µM与3.1 µM；同时该化合物表现出较低的细胞毒性，选择性指数大于100。本研究结果表明，石蒜碱是抗疟药物研发的潜在先导化合物。