BIOASSAY-GUIDED FRACTIONATION OF TITHONIA DIVERSIFOLIA SECONDARY METABOLITES AGAINST TRYPANOSOMA BRUCEI

Human African Trypanosomiasis (HAT, or “sleeping sickness”) is a fatal vector-borne neglected disease caused by the protozoan pathogen Trypanosoma brucei (Tb).1 It is endemic in sub-Saharan Africa and is introduced into the mammalian host by the bite of an infected Tsetse fly (Glossina spp., family Glossinidae). HAT is caused by two distinct subspecies of T. brucei, T. b. gambiense (West Africa; Tbg) and T. b. rhodesiense (East Africa; Tbr), and both forms begin with a haemolymphatic stage and become fatal when the trypanosomes invade the central nervous system (CNS). HAT threatens primarily rural populations with poor medical care and is one of the very few infectious diseases with a mortality rate of 100% if left untreated.Currently existing therapies are either largely based on drugs that are extremely toxic and prone to show severe side effects, or they are not sufficiently available or applicable to the most seriously affected people, where the parenteral administration is inappropriate due to the poor medical infrastructures. Therefore,the search for novel active principles and lead structures for the discovery and development of cost-effective new drugsis hence an extremely urgent task. Medicinal plants represent nowadays a powerful tool for discovery of new lead compounds and standardized herbal medicines against trypanosomiasis.2In Africa, plants have been used traditionally for centuries and are still widely employed to treat sleeping sickness. However, little is known about the treatment of HAT with plant- derived drugs and no trypanocidal molecule from natural origin is currently used against T. brucei infections.3 Therefore, it is of prime importance to investigate plants used in African traditional medicine to treat parasitic diseases. One of them, Tithonia diversifolia (Hemsl.) A. Gray (Asteraceae), known as Mexican sunflower, a shrub or tree widespread distributed in tropical areas of South America, Asia and Africa is commonly used in the traditional medicine by local ethnic groups for treating diabetes, microbiological infections, snakebites, and malaria.4Focusing on the secondary metabolites from T. diversifolia, most reports highlight the sesquiterpene lactones (STL) as the prominent group. Among them, tagitinins are the most representatives in T. diversifolia, with tagitinin C being the lead compound.On the basis of the above-illustrated therapeutic potential, secondary metabolites with antitrypanosomal activity were identified through bioassay-guided fractionation and structurally elucidated by NMR and MS techniques. To achieve these objectives, extracts of various polarities were prepared from the aerial parts of T. diversifolia, and screened against the trypomastigote form of T. brucei (TC221 cell line). The results of this study will be discussed. References 1. Jacobs, R. T.; Nare, B.; Phillips, M. A. Curr. Top. Med. Chem. 2011, 11, 1255−1274. 2. Scotti, L.; Mendonça, F.J.; da Silva, M.S.; Scotti, M.T. Curr. Protein Pept. Sci. 2016, 17, 243-259. 3. Hannaert, V. Planta Med. 2011, 77, 586–597. 4. Orsomando, G.; Agostinelli, S.; Bramucci, M.; Cappellacci, L.; Damiano, S.; Lupidi, G.; Maggi, F.; Ngahang Kamte, S.L.; Biapa Nya, P.C.; Papa, F.; Petrelli, D.; Quassinti, L.; Sorci, L.; Vitali, L.A.; Petrelli, R. Ind. Crops Prod. 2016, 85, 181–189.