Background: Chagas disease is a potentially fatal disease caused by the parasite Trypanosoma cruzi. There is growing scientific interest in finding new and better therapeutic alternatives for this disease’s treatment. Methods: A total of 81 terpene compounds with potential trypanocidal activity were screened and found to have potential T. cruzi cysteine synthase (TcCS) inhibition using molecular docking, molecular dynamics, ADME and PAIN property analyses and in vitro susceptibility assays. Results: Molecular docking analyses revealed energy ranges from −10.5 to −4.9 kcal/mol in the 81 tested compounds, where pentacyclic triterpenes were the best. Six compounds were selected to assess the stability of the TcCS–ligand complexes, of which lupeol acetate (ACLUPE) and α-amyrin (AMIR) exhibited the highest stability during 200 ns of molecular dynamics analysis. Such stability was primarily due to their hydrophobic interactions with the amino acids located in the enzyme’s active site. In addition, ACLUPE and AMIR exhibited lipophilic characteristics, low intestinal absorption and no structural interferences or toxicity. Finally, selective index for ACLUPE was >5.94, with moderate potency in the trypomastigote stage (EC50 = 15.82 ± 3.7 μg/mL). AMIR’s selective index was >9.36 and it was moderately potent in the amastigote stage (IC50 = 9.08 ± 23.85 μg/mL). Conclusions: The present study proposes a rational approach for exploring lupeol acetate and α-amyrin terpene compounds to design new drugs candidates for Chagas disease.

Chagas disease (ChD), caused by Trypanosoma cruzi, is endemic in American countries and an estimated 8 million people worldwide are chronically infected. Currently, only two drugs are available for therapeutic use against T. cruzi and their use is controversial due to several disadvantages associated with side effects and low compliance with treatment. Therefore, there is a need to search for new tripanocidal agents. Natural products have been considered a potential innovative source of effective and selective agents for drug development to treat T. cruzi infection. Recently, our research group showed that hexanic extract from Clethra fimbriata (CFHEX) exhibits anti-parasitic activity against all stages of T. cruzi parasite, being apoptosis the main cell death mechanism in both epimastigotes and trypomastigotes stages. With the aim of deepening the understanding of the mechanisms of death induced by CFHEX, the metabolic alterations elicited after treatment using a multiplatform metabolomics analysis (RP/HILIC-LC-QTOF-MS and GC-QTOF-MS) were performed. A total of 154 altered compounds were found significant in the treated parasites corresponding to amino acids (Arginine, threonine, cysteine, methionine, glycine, valine, proline, isoleucine, alanine, leucine, glutamic acid, and serine), fatty acids (stearic acid), glycerophospholipids (phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine), sulfur compounds (trypanothione) and carboxylic acids (pyruvate and phosphoenolpyruvate). The most affected metabolic pathways were mainly related to energy metabolism, which was found to be decrease during the evaluated treatment time. Further, exogenous compounds of the triterpene type (betulinic, ursolic and pomolic acid) previously described in C. fimbriata were found inside the treated parasites. Our findings suggest that triterpene-type compounds may contribute to the activity of CFHEX by altering essential processes in the parasite.

Chagas disease, a worldwide public health concern, is a chronic infection caused by Trypanosoma cruzi. Considering T. cruzi chronic persistence correlates with CD4+ and CD8+ T cell dysfunction and the safety and efficacy profiles of Benznidazol and Nifurtimox, the two drugs currently used for its etiological treatment, are far from ideal, the search of new trypanocidal treatment options is a highly relevant issue. Therefore, the objective of this work was to evaluate the trypanocidal effect and cytokine production induction of three extracts (hexane, dichloromethane and hydroalcoholic) obtained from Clethra fimbriata, a plant traditionally used as a febrifuge in Colombia. Additionally, the extracts' major components with the highest trypanocidal activity were determined. It was evidenced C. fimbriata hexane extract exhibited the highest activity capable of inhibiting the three parasite developmental stages with an IC50/EC50 of 153.9 ± 29.5 (epimastigotes), 39.3 ± 7.2 (trypomastigotes), and 45.6 ± 10.5 (amastigotes) μg/mL, presenting a low cytotoxicity in VERO cells with a selectivity index ranging from 6.49 to 25.4. Moreover, this extract induced trypomastigote apoptotic death and inhibited parasite cell infection. The extract also induced IFN-γ and TNF production in CD4+ and CD8+ T cells, as well as de novo production of the cytotoxic molecules granzyme B and perforin in CD8+ T cells from healthy donors. Fatty acids and terpenes represented C. fimbriata key compounds. Thus, the trypanocidal activity and cytokine production induction of the hexane extract may be associated with terpene presence, particularly, triterpenes.

Chagas disease is caused by Trypanosoma cruzi, and it is an important cause of morbidity and mortality in Latin America. There are no vaccines, and the chemotherapy available to treat this infection has serious side effects. In a search for alternative treatments, we determined the in vitro susceptibility of epimastigote and trypomastigote forms of T. cruzi and the cytotoxic effects on peripheral blood mononuclear cells (PBMCs) of ethanolic extracts obtained from six different plant species. The ethanolic extracts of Ageratina vacciniaefolia, Clethra fimbriata and Siparuna sessiliflora showed antiprotozoal activity against epimastigotes and low cytotoxicity in mammalian cells. However, only the ethanolic extract of C. fimbriata showed activity against T. cruzi trypomastigotes, and it had low cytotoxicity in PBMCs. An analysis on the phytochemical composition of C. fimbriata extract showed that its metabolites were primarily represented by two families of compounds: flavonoids and terpenoids. Lastly, we analyzed whether the A. vacciniaefolia, C. fimbriata, or S. sessiliflora ethanolic extracts induced IFN-γ or TNF-α production. Significantly, ethanolic extracts of C. fimbriata induced TNF-α production and S. sessiliflora induced both cytokines. In addition, C. fimbriata and S. sessiliflora induced the simultaneous secretion of IFN-γ and TNF-α in CD8+ T cells. The antiprotozoal and immunomodulatory activity of C. fimbriata may be related to the presence of flavonoid and triterpene compounds in the extract. Thus, these findings suggest that C. fimbriata may represent a valuable source of new bioactive compounds for the therapeutic treatment of Chagas disease that combines trypanocidal activity with the capacity to boost the immune response.

Basado en el conocimiento etnobotánico de comunidades campesinas del Tolima, se evaluó la actividad biológica del extracto acuoso de las hojas de Casearia corymbosa sobre la germinación de semillas de Passiflora edulis var. edulis (Gulupa). Se siguió el método tradicional para la obtención del extracto acuoso, el cual fue diluido varias veces para preparar 12 tratamientos experimentales que fueron utilizados un ensayo de germinación (in vitro) y comparados con 3 tratamientos control (GA3) y 2 tratamientos control con agua destilada. Se realizó una prueba de tetrazolium para determinar la viabilidad de las semillas y después se montó un ensayo in vitro, de diseño DCA, con 17 tratamientos y 1700 semillas. El porcentaje de germinación (G%) se midió cada 10 días durante 70 días y los resultados se analizaron estadísticamente con el programa R (2.8.1.). Se encontraron diferencias muy significativas entre los tratamientos con una prueba ANAVA y se determinó con una prueba LSD, que los 2 mejores tratamientos no fueron diferentes entre sí, pero si fueron diferentes del resto de tratamientos. Los mejores resultados en el G% alcanzaron el 94% y 81%. Los resultados sustentan la hipótesis de investigación, la cual se relaciona con la presencia de promotores de la germinación en el extracto de las hojas de C. corymbosa, que pueden ser tan efectivos como el GA3 en la promoción de la germinación.

A los extractos, fracciones y subfracciones obtenidos de hojas, flores y corteza de Bursera tomentosa (Jacq.) Triana & Planch., Burseraceae, se les evalúo su actividad citotóxica preliminar frente a las líneas celulares CSC-1595 y Colo 205, siguiendo el método de fraccionamiento guiado por bioensayo de citotoxicidad MTT. Los resultados obtenidos de esta prueba muestran a la subfracción en diclorometano-metanol (9.5:0.5) obtenida de la fracción acetato de etilo del extracto en éter de petróleo de hojas, como la que presentó las sustancias bioactivas con una marcada actividad citotóxica, con porcentajes de viabilidad del 3% y 15.3% a la concentración 30 µg/mL en las líneas tumorales humanas Colo 205 y CSC-1595 respectivamente.

In vitro cytotoxicity of extracts and fractions of Bursera tomentosa (Jacq.) Triana & Planch., Burseraceae, against human tumor cell. To the extracts, fractions and subfractions obtained from leaves, flowers and bark of Bursera tomentosa (Jacq.) Triana & Planch., Burseraceae, its preliminary cytotoxic activity against to the cellular lines CSC-1595 and Colo 205 were evaluated, following the MTT method. The results showed that dichloromethane-methanol (9.5:0.5) subfraction obtained of ethyl acetate part from petroleum extract of leaves, like to display the bioactives substances with a strong cytotoxic activity, showing viability percentage of 3% and 15,3% to the concentration 30 mu g/mL in human tumor cellular lines Colo 205 and CSC-1595 respectively.

De los extractos lipofílicos tanto de hojas como de flores, se aislaron e identificaron dos derivados del kaurano: el ent-kauran-16B-ol y el entkauran-] 6,20-diol y, dos flavonas metoxiladas: la 5-hidroxi-7,4'-dimetoxiflavona y la 5-hidroxi-3,7,4'-trimetoxi-flavona, Los dos diterpenos confirman la ubicación taxonómica de dicha especie según King y Robinson.

Resumen es: La leishmaniosis es considerada como una importante causa de morbilidad y mortalidad a nivel mundial, especialmente en paises tropicales. Las formas cuta...

Bursera graveolens (Burseraceae), known in Colombia as "sasafrás", is useful for its medicinal properties and is rich in secondary metabolites. In our research, we carried out antimicrobial tests of several fractions and ethanolic extracts from aerial parts against Bacillus subtilis and Staphylococcus aureus, that showed growth inhibitory activity when applied at 250 mg/mL for extracts and 150 mg/mL for fractions. We carried out an antiinflamatory assay also, that showed 71% of inhibition by extracts (81% of Indomethacin) and 70% of inhibition by fractions (78% of Indomethacin). Phytochemical investigation of the bark of Bursera graveolens (Burseraceae) yielded three tetracyclic triterpene acids that have oxygenation in C-3, carboxylic acid in C-21 and unsaturation in C-24 and have been identified as 3-oxotirucalla-8,24-dien-21-oic acid (b-elemonic acid), 3a-hydroxytirucalla-8,24-dien-21-oic acid (a-elemolic acid) and 3a-hydroxytirucalla-7,24-dien-21-oic acid. The isolated compounds were identified using spectroscopic methods including one and two-dimensional Nuclear Magnetic Resonance (COSY, HMQC, HMBC, NOESY) experiments and comparison with published data. This is the first report of the isolated compounds in Bursera graveolens and they have a very important chemotaxonomic significance within the Burseraceae family and related families from the order Rutales.

From leaves and flowers of Ageratina vacciniaefolia [1-7] we have isolated several compounds: a flavonoid, a diterpene [8] and a new compound identified as b-D-glucopyranosil ester of (-)17-(bglucopiranosyloxyl)- 16-hydroxy-kauran-19-oic acid (see the formula).[...]

From leaves and flowers of Ageratina vacciniaefolia we have isolated several compounds: a flavonoid, a diterpene and a new compound identified as (-)-b-D-18–glucopiranosyl-9,15-dihydroxy kaurenoate (see the formula).[...]

From the leaves of Conyza trihecatactis we have isolated the labdane-type diterpenes and diterpene xylosides ent-sclareol, ent-3β-hydroxymanool, ent-manool 13-O-β-d-xylopyranoside and ent-sclareol 13-O-β-d-xylopyranoside. Structure elucidation was achieved by spectroscopic methods.

13-epi-Cyclosclareol, a novel labdane-type diterpene with a cyclopropane ring has been isolated from Gnaphalium pellitum as well as from Gnaphalium graveolens. Structure elucidation was achieved by spectroscopic methods. The known diterpenes (−)-16-kauren-19-oic acid, (−)-11β-acetoxy-16-kauren-19-oic acid, 13-epi-sclareol and a mixture of sitosterol and stigmasterol were also isolated.

The effect of hertzian contact pressure on the friction coefficient of self-lubricating boric acid (H3BO3) films was investigated by sliding steel and ceramic balls against boric oxide (B2O3) coated steel and ceramic disks under a wide range of contact loads. Self-lubricating H3BO3 films result from a spontaneous chemical reaction between water molecules and B2O3 coatings in humid air. Mean initial hertzian contact pressures in the range 0.31–1.6 GPa were created between balls and B2O3-coated disks by varying the applied load and the radius of the balls. It was demonstrated that an inverse relationship exists between friction coefficient and hertzian contact pressure. Using the hertzian contact model, we estimated that the shear strength of H3BO3 films was approximately 22.9 MPa, which is comparable with 24.8 MPa reported for MoS2.

A novel ε-lactone characterized as ε-palmitolactone, two known flavones, 5-hydroxy-7,8,3′,4′-tetramethoxyflavone and 5-hydroxy 6,7,3′,4′-tetramethoxyflavone, and two sterols, stigmasterol and dehydrostigmasterol, were isolated from dried leaves and flowers of Ageratina viscosa.

A novel ε-lactone characterized as ε-palmitolactone, two known flavones, 5-hydroxy-7,8,3′,4′-tetramethoxyflavone and 5-hydroxy 6,7,3′,4′-tetramethoxyflavone, and two sterols, stigmasterol and dehydrostigmasterol, were isolated from dried leaves and flowers of Ageratina viscosa .