Native argentine Asteraceae as a source of extracts and sesquiterpene lactones active against Trypanosoma cruzi.

SOSA ANDREA MABEL; SALAMANCA CAPUSIRI EFRAIN; AMAYA SUSANA; PALMA CAMILA; GILABERT MIGUEL; VERA NANCY ROXANA; BARDON, ALICIA; GIMENEZ ALBERTO

BUENOS AIRES

Congreso; Drug Discovery for Neglected Diseases International Congress 2018 4th Scientific Meeting of the Research Network Natural Products against Neglected Diseases; 2018

IQUIMEFA,CONICET, UBA y RESNEt NP ND

Chagas disease is a potentially life-threatening illness caused by the parasite Trypanosoma cruzi. Currently, there aretwo therapeutic options for the treatment of the disease: benznidazole and nifurtimox. Both drugs have low or noefficacy in the chronic states of the disease, present regional variations of effectiveness and side effects that lead tothe interruption of treatment in a high percentage of patients. By reason of, new low-cost drugs, more effective andwith lower toxicity are needed [1]. Natural products (NP), were not only the origin of many drugs in the past, but theystill continue to provide unique structural diversity in comparison to standard combinatorial chemistry, offeringopportunities for the discovery of lead compounds [2]. Sesquiterpene lactones (SLs) are a group of NP mainly foundin the Asteraceae family, which present interesting biological activities, i.e., antitumor [3], anti-inflammatory [4],antiparasitic [5], among others.With the aim of continuing the study on antiparasitic properties of Asteraceae from Argentina, sixteen plants extracts,three chromatographic fractions (CF) and twelve SLs, were evaluated in vitro against Trypanosoma cruzi epimastigotesisolated from patients with Chagas disease. The toxicity against HeLa cells to determinate the selectivity index (SI) foreach substance, was also evaluated.Extracts and pure compounds were obtained from three plants: Elephantupus mollis, Centratherum punctatum yVernonanthura nebularum. SLs were isolated and purified employing RP-HPLC and identified through spectroscopicmethods. Trypanocidal and cytotoxic activities were determinate with a colorimetric microassay and read in amicroplate reader.All tested samples showed a moderate to strong trypanocidal activity with IC50 values between 47.4 and 0.35 µg/mL. Thebest SI (IC50HELA/ IC50PARASITE) were obtained for SLs 2, 3, 7 (isolated from V. nebularum) and 13 (isolated from E. mollis) andCF II and III (belong to V. nebularum) with SI values of 17.45, 14.30, 17.63, 22.84, 19.23 and 25.64, respectively. Theseresults showed that the plants studied are a promising source of trypanocidal products, being the pure compounds themost actives with IC50 values close to the IC50 values of the reference drugs employed (nifurtimox IC50 = 1.8 ± 0.2 μg/mL;benznidazole (IC50 = 10.5 ± 2.5 μg/mL). Most of the extracts were also active. Additionally, a study of structure-activityrelationship will be carried out to establish the physical-chemical parameters the afore mentioned activity is based on.Even more assays against other T. cruzi stages are needed; these compounds, fractions and extracts may providevaluable leads for the development of new drugs and formulations against this neglected parasitic disease.