Irungu Beatrice N, Adipo Nicholas, Orwa Jennifer A, Kimani Francis, Heydenreich Matthias, Midiwo Jacob O, Martin Björemark Per, Håkansson Mikael, Yenesew Abiy, Erdélyi Máté
Centre for Traditional Medicine and Drug Research, Kenya Medical Research Institute, P.O. Box 54840-00200, Nairobi, Kenya; Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg SE-41296, Sweden.
Centre for Traditional Medicine and Drug Research, Kenya Medical Research Institute, P.O. Box 54840-00200, Nairobi, Kenya.
J Ethnopharmacol. 2015 Nov 4;174:419-25. doi: 10.1016/j.jep.2015.08.039. Epub 2015 Aug 28.
Turraea robusta and Turraea nilotica are African medicinal plants used for the treatment of a wide variety of diseases, including malaria. The genus Turraea is rich in limonoids and other triterpenoids known to possess various biological activities.
From the stem bark of T. robusta six compounds, and from various parts of T. nilotica eleven compounds were isolated by the use of a combination of chromatographic techniques. The structures of the isolated compounds were elucidated using NMR and MS, whilst the relative configuration of one of the isolated compounds, toonapubesin F, was established by X-ray crystallography. The antiplasmodial activities of the crude extracts and the isolated constituents against the D6 and W2 strains of Plasmodium falciparum were determined using the semiautomated micro dilution technique that measures the ability of the extracts to inhibit the incorporation of (G-(3)H, where G is guanine) hypoxanthine into the malaria parasite. The cytotoxicity of the crude extracts and their isolated constituents was evaluated against the mammalian cell lines African monkey kidney (vero), mouse breast cancer (4T1) and human larynx carcinoma (HEp2).
The extracts showed good to moderate antiplasmodial activities, where the extract of the stem bark of T. robusta was also cytotoxic against the 4T1 and the HEp2 cells (IC50<10 μg/ml). The compounds isolated from these extracts were characterized as limonoids, protolimonoids and phytosterol glucosides. These compounds showed good to moderate activities with the most active one being azadironolide, IC50 2.4 ± 0.03 μM and 1.1 ± 0.01 μM against the D6 and W2 strains of Plasmodium falciparum, respectively; all other compounds possessed IC50 14.4-40.5 μM. None of the compounds showed significant cytotoxicity against vero cells, yet four of them were toxic against the 4T1 and HEp2 cancer cell lines with piscidinol A having IC50 8.0 ± 0.03 and 8.4 ± 0.01 μM against the 4T1 and HEp2 cells, respectively. Diacetylation of piscidinol A resulted in reduced cytotoxicity.
From the medicinal plants T. robusta and T. nilotica, twelve compounds were isolated and characterized; two of the isolated compounds, namely 11-epi-toonacilin and azadironolide showed good antiplasmodial activity with the highest selectivity indices.
粗壮杜瑞木和尼罗杜瑞木是非洲药用植物，用于治疗包括疟疾在内的多种疾病。杜瑞木属富含柠檬苦素和其他已知具有多种生物活性的三萜类化合物。
采用多种色谱技术相结合的方法，从粗壮杜瑞木的茎皮中分离出6种化合物，从尼罗杜瑞木的不同部位分离出11种化合物。利用核磁共振（NMR）和质谱（MS）对分离得到的化合物结构进行了鉴定，同时通过X射线晶体学确定了其中一种分离化合物香椿苷F的相对构型。使用半自动微量稀释技术测定粗提物和分离成分对恶性疟原虫D6和W2菌株的抗疟活性，该技术用于测量提取物抑制（G-（3）H，其中G是鸟嘌呤）次黄嘌呤掺入疟原虫的能力。评估粗提物及其分离成分对哺乳动物细胞系非洲绿猴肾细胞（vero）、小鼠乳腺癌细胞（4T1）和人喉癌细胞（HEp2）的细胞毒性。
提取物表现出良好到中等的抗疟活性，其中粗壮杜瑞木茎皮提取物对4T1和HEp2细胞也具有细胞毒性（IC50<10μg/ml）。从这些提取物中分离出的化合物被鉴定为柠檬苦素、原柠檬苦素和植物甾醇糖苷。这些化合物表现出良好到中等的活性，其中活性最高的是阿扎地诺内酯，对恶性疟原虫D6和W2菌株的IC50分别为2.4±0.03μM和1.1±0.01μM；所有其他化合物的IC50为14.4-40.5μM。没有一种化合物对vero细胞表现出显著的细胞毒性，但其中四种对4T1和HEp2癌细胞系有毒性，杀鱼菌素A对4T1和HEp2细胞的IC50分别为8.0±0.03和8.4±0.01μM。杀鱼菌素A的二乙酰化导致细胞毒性降低。
从药用植物粗壮杜瑞木和尼罗杜瑞木中分离并鉴定了12种化合物；其中两种分离化合物，即11-表香椿素和阿扎地诺内酯表现出良好的抗疟活性，且选择性指数最高。
