Sut Stefania, Dall'Acqua Stefano, Baldan Valeria, Ngahang Kamte Stephane L, Ranjbarian Farahnaz, Biapa Nya Prosper C, Vittori Sauro, Benelli Giovanni, Maggi Filippo, Cappellacci Loredana, Hofer Anders, Petrelli Riccardo
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Fitoterapia. 2018 Jan;124:145-151. doi: 10.1016/j.fitote.2017.11.002. Epub 2017 Nov 13.
Tithonia diversifolia (Asteraceae), is used as traditional medicine in tropical countries for the treatment of various diseases, including malaria. Although numerous studies have assessed the antimalarial properties, nothing is known about the effect of T. diversifolia extracts on trypanosomiasis. In this study extracts of T. diversifolia aerial parts were evaluated for their bioactivity against Trypanosoma brucei. The activity was studied against bloodstream forms of T. brucei (TC221), as well as against mammalian cells (BALB/3T3 mouse fibroblasts), as a counter-screen for toxicity. Both methanolic and aqueous extracts showed significant effects with IC values of 1.1 and 2.2μg/mL against T. brucei (TC221) and 5.2 and 3.7μg/mL against BALB/3T3 cells, respectively. A bioassay-guided fractionation on the methanolic extract yielded in identification of active fractions (F8 and F9) with IC values of 0.41 and 0.43μg/mL, respectively, against T. brucei (TC221) and 1.4 and 1.5μg/mL, respectively, against BALB/3T3 cells,. The phytochemical composition of the extracts and the purified fractions were investigated using HPLC-ESI-MS/MS and 1D and 2D NMR spectra showing the presence of sesquiterpene lactones that in turn were subjected to the isolation procedure. Tagitinin A and C were rather active but the latter presented a very strong inhibition on T. brucei (TC221) with an IC value of 0.0042μg/mL. This activity was 4.5 times better than that of the reference drug suramin. The results of this study shed light on the antitrypanosomal effects of T. diversifolia extracts and highlighted tagitinin C as one of the possible responsible for this effect. Further structure activity relationships studies on tagitinins are needed to consider this sesquiterpenes as lead compounds for the development of new antitrypanosomal drugs.
臭草（菊科）在热带国家被用作传统药物，用于治疗包括疟疾在内的各种疾病。尽管众多研究评估了其抗疟特性，但关于臭草提取物对锥虫病的影响却一无所知。在本研究中，对臭草地上部分的提取物针对布氏锥虫的生物活性进行了评估。研究了其对布氏锥虫（TC221）血流形式的活性，以及对哺乳动物细胞（BALB/3T3小鼠成纤维细胞）的活性，作为毒性的反向筛选。甲醇提取物和水提取物均显示出显著效果，对布氏锥虫（TC221）的IC值分别为1.1和2.2μg/mL，对BALB/3T3细胞的IC值分别为5.2和3.7μg/mL。对甲醇提取物进行生物测定导向的分级分离，鉴定出活性级分（F8和F9），对布氏锥虫（TC221）的IC值分别为0.41和0.43μg/mL，对BALB/3T3细胞的IC值分别为1.4和1.5μg/mL。使用HPLC-ESI-MS/MS以及一维和二维核磁共振光谱对提取物和纯化级分的植物化学成分进行了研究，结果显示存在倍半萜内酯，随后对其进行了分离程序。tagitinin A和C具有相当的活性，但后者对布氏锥虫（TC221）表现出非常强的抑制作用，IC值为0.0042μg/mL。该活性比参考药物苏拉明高4.5倍。本研究结果揭示了臭草提取物的抗锥虫作用，并突出了tagitinin C作为可能导致这种作用的成分之一。需要对tagitinin进行进一步的构效关系研究，以将这种倍半萜作为开发新型抗锥虫药物的先导化合物。
