Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
J Ethnopharmacol. 2013 Mar 7;146(1):417-22. doi: 10.1016/j.jep.2013.01.013. Epub 2013 Jan 18.
Zanthoxylum capense Thunb. (Rutaceae) is a medicinal plant traditionally used in Mozambique to treat tuberculosis.
The main aim of the study was to find antimycobacterial lead compounds from Zanthoxylum capense. Another goal was to provide scientific validation for the use of this plant in traditional medicine.
By bioassay-guided fractionation, 16 compounds were isolated and screened for their in vitro antimycobacterial activity against two different strains of Mycobacterium tuberculosis. Their in vitro cytotoxicity to human THP-1 macrophages was also assessed. The compounds with favourable selectivity index values (SI>10) were further investigated for their ability to inhibit the growth of Mycobacterium tuberculosis H37Rv in an intracellular macrophage model of infection.
The best results were obtained for a benzophenanthridine alkaloid, decarine (1), and an N-isobutylamide, N-isobutyl-(2E,4E)-2,4-tetradecadienamide (15), which showed high activity against Mycobacterium tuberculosis H37Rv (MIC of 1.6 μg/ml), and a low macrophage cytotoxicity (IC50>60 μg/ml), indicating considerable selective activity. The benzophenanthridine alkaloid 6-acetonyldihydronitidine (6) revealed cytotoxicity (IC50 1.7 μg/ml), despite the determined MIC of 6.2-12.5 μg/ml. In infected macrophages, decarine (1) was able to reduce bacterial survival by almost two log units at a concentration of 6.2 μg/ml 5 days post-drug exposure. Compound 15 exhibited an intermediate activity at drug concentrations ranging from 6.2 to 25 μg/ml.
The high antimycobacterial activity of decarine found, both in vitro and ex vivo against mycobacteria, and the low cytotoxicity towards human macrophages indicate that it may be valuable as a lead scaffold for the development of anti-TB drugs.
山蒟（芸香科）是一种药用植物，传统上用于莫桑比克治疗肺结核。
该研究的主要目的是从山蒟中寻找抗分枝杆菌的先导化合物。另一个目标是为该植物在传统医学中的应用提供科学依据。
通过生物活性指导的分级分离，从山蒟中分离出 16 种化合物，并对其体外抗两种不同结核分枝杆菌菌株的活性进行了筛选。还评估了它们对人 THP-1 巨噬细胞的体外细胞毒性。对具有良好选择性指数值（SI>10）的化合物进行了进一步研究，以评估它们抑制分枝杆菌感染的人巨噬细胞内生长的能力。
苯并菲啶生物碱 decarine（1）和 N-异丁基酰胺 N-异丁基-（2E，4E）-2,4-十四碳二烯酰胺（15）的效果最好，对结核分枝杆菌 H37Rv 表现出高活性（MIC 为 1.6 μg/ml），且对巨噬细胞的细胞毒性低（IC50>60 μg/ml），表明具有相当大的选择性。苯并菲啶生物碱 6-乙酰基二氢去甲烟碱（6）显示出细胞毒性（IC50 为 1.7 μg/ml），尽管确定的 MIC 为 6.2-12.5 μg/ml。在感染的巨噬细胞中，decarine（1）在药物暴露后 5 天，在 6.2 μg/ml 的浓度下，能够将细菌存活数减少近两个对数单位。化合物 15 在 6.2 至 25 μg/ml 的药物浓度范围内表现出中等活性。
在体外和体内对分枝杆菌的高抗分枝杆菌活性，以及对人巨噬细胞的低细胞毒性表明，它可能是一种有价值的抗结核药物的先导支架。
