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Cancer is one of the most important causes of death worldwide. Solid tumors represent the vast majority of cancers (>90%), and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpenes are a group of natural compounds that have shown a wide range of biological activities, including cytotoxic and antiparasitic activity, among others. The antiproliferative activity of natural sesquiterpenes, tessaric acid, ilicic acid, and ilicic alcohol and their semisynthetic derivatives against HeLa, T-47D, WiDr, A549, HBL-100, and SW1573 cell lines were evaluated. The effect of the compounds on Trypanosoma cruzi epimastigotes was also assessed. The selectivity index was calculated using murine splenocytes. Derivatives 13 and 15 were the most antiproliferative compounds, with GI50 values ranging between 5.3 (±0.32) and 14 (±0.90) μM, in all cell lines tested. The presence of 1,2,3-triazole groups in derivatives 15−19 led to improvements in activity compared to those corresponding to the starting natural product (3), with GI50 values ranging between 12 (±1.5) and 17 (±1.1) μM and 16 being the most active compound. In relation to the anti-T. cruzi activity, derivatives 7 and 16 obtained from tessaric acid and ilicic acid were among the most active and selective compounds with IC50 values of 9.3 and 8.8 µM (SI = 8.0 and 9.4), respectively.

The sesquiterpene lactones eupatoriopicrin, estafietin, eupahakonenin B and minimolide have been isolated from Argentinean Astearaceae species and have been found to be active against Trypanosoma cruzi epimastigotes. The aim of this work was to evaluate the activity of these compounds by analyzing their effect against the stages of the parasites that are infective for the human. Even more interesting, we aimed to determine the effect of the most active and selective compound on an in vivo model of T. cruzi infection. Eupatoriopicrin was the most active against amastigotes and tripomastigotes (IC 50 = 2.3 µg/mL, and 7.2 µg/mL, respectively) and displayed a high selectivity index. This compound was selected to study on an in vivo model of T. cruzi infection. The administration of 1 mg/kg/day of eupatoriopicrin for five consecutive days to infected mice produced a significant reduction in the parasitaemia levels in comparison with non-treated animals (area under parasitaemia curves 4.48 vs. 30.47, respectively). Skeletal muscular tissues from eupatopicrin-treated mice displayed only focal and interstitial lymphocyte inflammatory infiltrates and small areas of necrotic; by contrast, skeletal tissues from T. cruzi infected mice treated with the vehicle showed severe lymphocyte inflammatory infiltrates with necrosis of the adjacent myocytes. The results indicate that eupatoriopicrin could be considered a promising candidate for the development of new therapeutic agents for Chagas disease.

Sesquiterpene lactones are naturally occurring compounds mainly found in the Asteraceae family. These types of plant metabolites display a wide range of biological activities, including antiprotozoal activity and are considered interesting structures for drug discovery. Four derivatives were synthesized from estafietin ( 1 ), isolated from Stevia alpina (Asteraceae): 11βH,13-dihydroestafietin ( 2 ), epoxyestafietin ( 3a and 3b ), 11βH,13-methoxyestafietin, ( 4 ) and 11βH,13-cianoestafietin. The antiprotozoal activity against Trypanosoma cruzi and Leishmania braziliensis of these compounds was evaluated. Epoxyestafietin was the most active compound against T. cruzi trypomastigotes and amastigotes (IC 50 values of 18.7 and 2.0 µg/mL, respectively). Estafietin ( 1 ) and 11βH,13-dihydroestafietin ( 2 ) were the most active and selective compounds on L. braziliensis promastigotes (IC 50 values of 1.0 and 1.3 μg/mL, respectively). The antiparasitic activity demonstrated by estafietin and some of its derivatives make them promising candidates for the development of effective compounds for the treatment of Chagas disease and leihsmaniasis.

Cancer is one of the most important causes of death worldwide. Solid tumors represent the great majority of cancers (>90%) and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpene lactones are a group of naturally occurring compounds that have displayed a diverse range of biological activities including cytotoxic activity. A series of oxygenated and oxy-nitrogenated derivatives ( 4 ⁻ 15 ) from the sesquiterpene lactones cumanin ( 1 ), helenalin ( 2 ), and hymenin ( 3 ) were synthesized. The silylated derivatives of helenalin, compounds 13 and 14 , were found to be the most active against tumor cell lines, with GI 50 values ranging from 0.15 to 0.59 μM. The ditriazolyl cumanin derivative ( 11 ) proved to be more active and selective than cumanin in the tested breast, cervix, lung, and colon tumor cell lines. This compound was the least toxic against splenocytes (CC 50 = 524.1 µM) and exhibited the greatest selectivity on tumor cell lines. This compound showed a GI 50 of 2.3 µM and a SI of 227.9 on WiDr human colon tumor cell lines. Thus, compound 11 can be considered for further studies and is a candidate for the development of new antitumor agents., Competing Interests: The authors declare no conflict of interest.