Trypanocidal Activity ofSmallanthus sonchifolius: Identification of Active Sesquiterpene Lactones by Bioassay-Guided Fractionation

Abstract

In order to find novel plant-derived biologically active compounds against Trypanosoma cruzi, we isolated, from the organic extract of Smallanthus sonchifolius, the sesquiterpene lactones enhydrin (1), uvedalin (2), and polymatin B (3) by bioassay-guided fractionation technique. These compounds showed a significant trypanocidal activity against the epimastigote forms of the parasite with IC50 values of 0.84 μM (1), 1.09 μM (2), and 4.90 μM (3). After a 24 h treatment with 10 μg/mL of enhydrin or uvedalin, parasites were not able to recover their replication rate. Compounds 1 and 2 showed IC50 values of 33.4 μM and 25.0 μM against T. cruzi trypomastigotes, while polymatin B was not active. When the three compounds were tested against the intracellular forms of T. cruzi, they were able to inhibit the amastigote replication with IC50 of 5.17 μM, 3.34 μM, and 9.02 μM for 1, 2, and 3, respectively. The cytotoxicity of the compounds was evaluated in Vero cells obtaining CC50 values of 46.5 μM (1), 46.8 μM (2), and 147.3 μM (3) and the selectivity index calculated. According to these results, enhydrin and uvedalin might have potentials as agents against Chagas disease and could serve as lead molecules to develop new drugs.

Germacranolide-type sesquiterpene lactones from Smallanthus sonchifolius with promising activity against Leishmania mexicana and Trypanosoma cruzi

“…Smallanthus sonchifolius leaves were processed by soaking in dichloromethane at room temperature for 30 min as previously described [ 28 ]. This extract was subjected to a bioassay-guided fractionation by sequential silica gel (70–230 mesh; Macherey-Nagel, Düren, Germany) column chromatography using a gradient of n- hexane (2 × 250 ml), n -hexane-ethyl acetate (1:1) (2 × 250 ml), ethyl acetate (2 × 250 ml), ethyl acetate-methanol (1:1) (2 × 250 ml), and methanol (2 × 250 ml) as mobile phase.…”

“…We have previously reported the cytotoxicity of six sesquiterpene lactones (STLs) isolated from S. sonchifolius in leukaemia and pancreatic cancer cells. Interestingly, one of those STLs was reported for the first time in nature [ 27 ], whilst the in vitro trypanocidal activity of the STLs enhydrin, uvedalin and polymatin B has been previously reported by our group [ 28 ]. In view of the results obtained, and considering the current drawbacks related to the treatment with trypanocidal drugs, this study was aimed at determining whether the STLs enhydrin and uvedalin are active in an animal model of the infection.…”

Computer-Aided Drug Design Using Sesquiterpene Lactones as Sources of New Structures with Potential Activity against Infectious Neglected Diseases

“…New antitrypanosomal SLs have been isolated through bioassay-guided techniques from the organic extract of Smallanthus sonchifolius , which provided three active compounds against epimastigotes of T. cruzi , enhydrin ( 54 ) (IC 50 0.84 μM), uvedalin ( 55 ) (IC 50 1.09 μM), and polymatin B ( 56 ) (IC 50 4.90 μM), of which only the first two compounds presented activity against T. cruzi trypomastigotes 33.4 μM and 25.0 μM, respectively, being proposed as lead molecules to develop new drugs for Chagas disease [ 69 ]. By this same methodology, peruvin ( 28 ) and psilostachyin ( 29 ) were tested with T. cruzi epimastigotes and gave low values of IC 50 6.2 μM and 4.4 μM, respectively, where 29 was more active on the trypomastigotes with an IC 50 of 2.7 μM compared with 200 μM reached by 28 [ 59 ].…”

Smallanthus sonchifolius

“…The sesquiterpene lactones enhydrin (1), uvedalin (2) and polymatin B from yacon showed signifi cant trypanocidal activity against the epimastigote forms of Trypanosoma cruzi with IC 50 values of 0.84 μM (1), 1.09 μM (2) and 4.90 μM (3), respectively (Frank et al 2013 ). After a 24 hour treatment with 10 μg/mL of enhydrin or uvedalin, the parasites were not able to recover their replication rate.…”