Kimani Njogu M, Matasyoh Josphat C, Kaiser Marcel, Brun Reto, Schmidt Thomas J
Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus Corrensstraße 48, D-48149 Münster, Germany.
Department of Chemistry, Egerton University, P.O. Box 536, Egerton, Nairobi 20115, Kenya.
Molecules. 2017 Apr 8;22(4):597. doi: 10.3390/molecules22040597.
Sleeping sickness or human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) threatening millions of peoples' lives with thousands infected. The disease is endemic in poorly developed regions of sub-Saharan Africa and is caused by the kinetoplastid "protozoan" parasite . The parasites are transmitted to humans through bites of infected tsetse flies of the genus . The few available drugs for treatment of this disease are highly toxic, difficult to administer, costly and unavailable to poor rural communities bearing the major burden of this infection. Therefore, the search for new efficacious, safe and affordable drugs is of high importance. O. Hoffm., an indigenous African plant of the Asteraceae family, has been extensively reported to be used ethno-medicinally as a treatment for malaria. Its crude extracts obtained with solvents of different polarity were screened in vitro for anti-protozoal activity and the dichloromethane extract was found to be particularly active against (IC = 0.17 µg/mL). Bioassay-guided chromatographic fractionation of the dichloromethane extract led to the isolation and identification of six elemanolide type sesquiterpene lactones: 8-desacylvernolide, vernolepin, vernomenin, vernodalol, vernodalin and 11,13-dihydrovernodalin. All these elemanolide sesquiterpene lactones showed in vitro anti-trypanosomal activity. They were also tested for cytotoxicity against mammalian cells (L6 cell line). Vernolepin, the main component in the extract, was also the most potent with an IC value of 0.05 µg/mL against trypomastigotes. This compound showed a selectivity index of 14.5, which makes it an interesting candidate for in vivo tests and determination of its mechanism of action.
昏睡病或人类非洲锥虫病（HAT）是一种被忽视的热带病（NTD），威胁着数百万人的生命，数千人受到感染。该病在撒哈拉以南非洲的欠发达地区流行，由动质体“原生动物”寄生虫引起。这些寄生虫通过感染的采采蝇属叮咬传播给人类。治疗这种疾病的可用药物很少，且毒性高、给药困难、成本高，贫困农村社区无法获得，而这些社区承担着这种感染的主要负担。因此，寻找新的有效、安全且负担得起的药物至关重要。菊科的非洲本土植物O. Hoffm.，已有大量报道称其在民族医学中用于治疗疟疾。用不同极性溶剂获得的其粗提物进行了体外抗原生动物活性筛选，发现二氯甲烷提取物对（IC = 0.17 µg/mL）特别有活性。对二氯甲烷提取物进行生物测定导向的色谱分离，导致分离并鉴定出六种榄烷型倍半萜内酯：8-去酰基佛诺内酯、佛诺平、佛诺门宁、佛诺达醇、佛诺达林和11,13-二氢佛诺达林。所有这些榄烷型倍半萜内酯均显示出体外抗锥虫活性。它们还针对哺乳动物细胞（L6细胞系）进行了细胞毒性测试。提取物中的主要成分佛诺平对锥鞭毛体的IC值为0.05 µg/mL，也是最有效的。该化合物的选择性指数为14.5，这使其成为体内试验及其作用机制测定的一个有吸引力的候选物。
