Effect of the Proximity to the Quintero-Puchuncaví Industrial Zone on Compounds Isolated from Baccharis macraei Hook. & Arn: Their Antioxidant and Cytotoxic Activity.

Baccharis macraei Hook. & Arn (Asteraceae), commonly known as Vautro, is found in the coastal areas of central-southern Chile, including the industrial zone of Quintero-Puchuncaví, known for the contamination of its soils with heavy metals, which together with other factors generate abiotic stress in plant species, against which they present defensive mechanisms. For this reason, the objective was to evaluate the effect of abiotic stress generated by the proximity of B. macraei to the industrial complex by assessing the physiological and metabolic states reported by the extracts and compounds isolated from the species, as well as the photosynthetic capacity, metal content and production, and antioxidant activity and cytotoxicity against tumorigenic cell lines of the phytoconstituents. To this end, B. macraei was collected at two different distances from the industrial complex, observing that the closer the species is, the greater the concentration of copper in the soil, generating a decrease in the rate of electron transport in situ, but an increase in antioxidant activity with low cytotoxicity. This activity could be due to the presence of flavonoids such as Hispidulin, Cirsimaritina, and Isokaempferida, as well as monoterpenes, oxygenated and non-oxygenated sesquiterpenes identified in this study.

Antitumoral Activity of Leptocarpha rivularis Flower Extracts against Gastric Cancer Cells.

Leptocarpha rivularis is a native South American plant used ancestrally by Mapuche people to treat gastrointestinal ailments. L. rivularis flower extracts are rich in molecules with therapeutic potential, including the sesquiterpene lactone leptocarpin, which displays cytotoxic effects against various cancer types in vitro. However, the combination of active molecules in these extracts could offer a hitherto unexplored potential for targeting cancer. In this study, we investigated the effect of L. rivularis flower extracts on the proliferation, survival, and spread parameters of gastric cancer cells in vitro. Gastric cancer (AGS and MKN-45) and normal immortalized (GES-1) cell lines were treated with different concentrations of L. rivularis flower extracts (DCM, Hex, EtOAc, and EtOH) and we determined the changes in proliferation (MTS assay, cell cycle analysis), cell viability/cytotoxicity (trypan blue exclusion assay, DEVDase activity, mitochondrial membrane potential MMP, and clonogenic ability), senescence (ß-galactosidase activity) and spread potential (invasion and migration assays using the Boyden chamber approach) in all these cells. The results showed that the DCM, EtOAc, and Hex extracts display a selective antitumoral effect in gastric cancer cells by affecting all the cancer parameters tested. These findings reveal an attractive antitumoral potential of L. rivularis flower extracts by targeting several acquired capabilities of cancer cells.

Cytotoxic Activity, Topoisomerase I Inhibition and In Silico Studies of New Sesquiterpene-aryl Ester Derivatives of (-) Drimenol.

In this study, we aimed to evaluate two sets of sesquiterpene-aryl derivatives linked by an ester bond, their cytotoxic activities, and their capacity to activate caspases 3/7 and inhibit human topoisomerase I (TOP1). A total of 13 compounds were synthesized from the natural sesquiterpene (-)-drimenol and their cytotoxic activity was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and an immortalized non-tumoral cell line (MCF-10). From the results, it was observed that 6a was the most promising compound due to its cytotoxic effect on three cancer cell lines and its selectivity, 6a was 100-fold more selective than 5-FU in MCF-7 and 20-fold in PC-3. It was observed that 6a also induced apoptosis by caspases 3/7 activity using a Capsase-Glo-3/7 assay kit and inhibited TOP1. A possible binding mode of 6a in a complex with TOP1-DNA was proposed by docking and molecular dynamics studies. In addition, 6a was predicted to have a good pharmacokinetic profile for oral administration. Therefore, through this study, it was demonstrated that the drimane scaffold should be considered in the search of new antitumoral agents.

Effect of Industrial Pollution in Puchuncaví Valley on the Medicinal Properties of Senecio fistulosus Poepp. ex Les (Asteraceae): Content of Phytoconstituents and Their Antioxidant and Cytotoxic Activities.

Senecio fistulosus, an endemic plant in Chile, is highly regarded for its medicinal properties and is popular in alternative medicine. It thrives even in polluted areas, like Puchuncaví Valley, Chile. Therefore, the study aimed to assess the impact of industrial pollution in Puchuncaví Valley, Chile, on the phytoconstituent content, as well as the antioxidant and cytotoxic activities, of S. fistulosus. Phenols, flavonoids, and anthraquinones content were measured, alongside the assessment of antioxidant activities. Additionally, a GC-MS analysis was conducted to profile the phytoconstituents, while the cytotoxic potential was evaluated in HT-29 and MCF-7 and cell line non-tumorigenic MCF-10. The Wild sample exhibited a greater concentration of phytoconstituents (0 to 169.48 mg·L-1) compared to the Commercial control (0 to 95.38 mg·L-1), directly correlating with its antioxidant activity. While the Wild species showed cytotoxic activity, the Commercial control demonstrated cytotoxic effects on MCF-10 and MCF-7. Noteworthy compounds identified were hexadecanoic acid (12.76 to 19.57% relative area) and (Z,Z,Z)-9,12,15-octadecatrienoic acid (18.36% relative area), with anticancer properties. In conclusion, the abiotic stress experienced by S. fistulosus led to higher phytoconstituent content and improved antioxidant activity when contrasted with the Commercial control. The Commercial species showed increased cytotoxic activity against both tumorigenic and non-tumorigenic cell lines.

Resveratrol Decreases the Invasion Potential of Gastric Cancer Cells.

The cancer-preventive agent Resveratrol (RSV) [3,5,4'-trihydroxytrans-stilbene] is a widely recognized antioxidant molecule with antitumoral potential against several types of cancers, including prostate, hepatic, breast, skin, colorectal, and pancreatic. Herein, we studied the effect of RSV on the cell viability and invasion potential of gastric cancer cells. AGS and MKN45 cells were treated with different doses of RSV (0-200 µM) for 24 h. Cell viability was determined using the Sulphorhodamine B dye (SRB) assay. For invasion assays, gastric cells were pre-treated with RSV (5-25 µM) for 24 h and then seeded in a Transwell chamber with coating Matrigel. The results obtained showed that RSV inhibited invasion potential in both cell lines. Moreover, to elucidate the mechanism implicated in this process, we analyzed the effects of RSV on SOD, heparanase, and NF-κB transcriptional activity. The results indicated that RSV increased SOD activity in a dose-dependent manner. Conversely, RSV significantly reduced the DNA-binding activity of NF-κB and the enzymatic activity of heparanase in similar conditions, which was determined using ELISA-like assays. In summary, these results show that RSV increases SOD activity but decreases NF-kB transcriptional activity and heparanase enzymatic activity, which correlates with the attenuation of invasion potential in gastric cancer cells. To our knowledge, no previous study has described the effect of RSV on heparanase activity. This article proposes that heparanase could be a key effector in the invasive events occurring during gastric cancer metastasis.

Evaluation of Antioxidant and Cytotoxic Activity of Hydro-Ethanolic Extracts Obtained from Steiractinia aspera Cuatrec.

In this work, the antioxidant activity of the hydro-ethanolic extracts of the leaves, flowers, and aerial parts of Steiractinia aspera Cuatrec, both fresh and post-distillation, was evaluated by ABTS+·, FRAP, H2O2 and DPPH assays. The cytotoxic activity was evaluated in MCF-7, MCF-10A and HT-29 cell lines. The hydro-ethanolic extracts were obtained by matrix solid-phase dispersion (MSPD) and ultrasound-assisted solvent extraction (SE). The fresh-leaf MSPD extract had the highest antioxidant activity, and the post-distillation leaf ultrasound-assisted SE extract had the highest cytotoxicity in the MCF-7 breast cancer cell line, although not selective, which was evaluated by sulforhodamine B assay. On the other hand, ROS was evaluated by flow cytometry which showed that post-distillation leaf extract is pro-oxidant. Chlorogenic acid, kaempferol-3-glucoside and quercetin were found in the fresh leaves' extracts, according to HPLC-DAD. PLC-DAD permitted the isolation of p-coumaric acid, E-3-(4-(((E)-3-(3,4-dihydroxyphenyl) acryloyl) oxy)-3-hydroxyphenyl) acrylic acid and a diglucosylated derivative of ursolic acid, which were analyzed by 1H and 13C NMR. Our results suggest that the fresh leaf extract of Steiractinia aspera Cuatrec has potential use for antioxidant applications.

Antioxidant and Anti-Proliferative Activity of Essential Oil and Main Components from Leaves of Aloysia polystachya Harvested in Central Chile.

The aim of this study was to determine, first, the chemical composition of Aloysia polystachya (Griseb) Moldenke essential oil, from leaves harvested in central Chile; and second, its antioxidant and cytotoxic activity. Eight compounds were identified via gas chromatography-mass spectrometry (GC-MS) analyses, with the most representative being R-carvone (91.03%), R-limonene (4.10%), and dihydrocarvone (1.07%). For Aloysia polystachya essential oil, antioxidant assays (2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2, ferric reducing antioxidant power (FRAP), and total reactive antioxidant potential (TRAP)) showed good antioxidant activity compared to commercial antioxidant controls; and anti-proliferative assays against three human cancer cell lines (colon, HT-29; prostate, PC-3; and breast, MCF-7) determined an IC50 of 5.85, 6.74, and 9.53 µg/mL, and selectivity indices of 4.75, 4.12, and 2.92 for HT-29, PC-3, and MCF-7, respectively. We also report on assays with CCD 841 CoN (colon epithelial). Overall, results from this study may represent, in the near future, developments for natural-based cancer treatments.

Chemical Composition, Antioxidant and Anticancer Activities of Leptocarpha rivularis DC Flower Extracts.

An evaluation of antioxidant and anticancer activity was screened in Leptocarpha rivularis DC flower extracts using four solvents (n-hexane (Hex), dichloromethane (DCM), ethyl acetate (AcOEt), and ethanol (EtOH)). Extracts were compared for total extract flavonoids and phenol contents, antioxidant activity (2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), ferric reducing antioxidant potential (FRAP), total reactive antioxidant properties (TRAP) and oxygen radical absorbance capacity (ORAC)) across a determined value of reduced/oxidized glutathione (GSH/GSSG), and cell viability (the sulforhodamine B (SRB) assay). The most active extracts were analyzed by chromatographic analysis (GC/MS) and tested for apoptotic pathways. Extracts from Hex, DCM and AcOEt reduced cell viability, caused changes in cell morphology, affected mitochondrial membrane permeability, and induced caspase activation in tumor cell lines HT-29, PC-3, and MCF-7. These effects were generally less pronounced in the HEK-293 cell line (nontumor cells), indicating clear selectivity towards tumor cell lines. We attribute likely extract activity to the presence of sesquiterpene lactones, in combination with other components like steroids and flavonoids.

In vitro antioxidant and antiproliferative effect of the extracts of Ephedra chilensis K Presl aerial parts.

BACKGROUND: Ephedra chilensis K Presl, known locally as pingo-pingo, is a Chilean endemic plant used in traditional medicine as an anti-inflammatory and used in other treatments. However, unlike for the other Ephedra species, there have been no reports on the antioxidant and cytotoxic effects of this plant. The present study aims to explore the potential applications of E. chilensis extract as a cytotoxic agent against in vitro cancer cell lines and to explore the relationship between this extract and antioxidant activity. METHODS: Total anthraquinone, flavonoid, and phenolic contents, as well as antioxidant activity (DPPH, FRAP, and TRAP assays) and cytotoxic effect on several cancer cell lines (MCF-7, PC-3, DU-145, and HT-29) were measured for the hexane, dichloromethane and ethanol extracts of E. chilensis. In addition, several correlations among the phytochemical content, antioxidant activity, and cytotoxic effect were evaluated. Finally, GC-MS analyses of the most active extracts were carried out to identify their major components and to relate these components to the cytotoxic effect. RESULTS: Antioxidant activity was found in the EtOH extracts of Ephedra, and the results were correlated with the phenolic content. For the cytotoxic activity, the non-polar extracts of E. chilensis had the highest antiproliferative effect for the MCF-7 and PC-3 cancer lines; the extract was shown to be up to three times more selective than doxorubicin. However, the cytotoxic effect was not correlated with the antioxidant activity. Lastly, the GC-MS analysis showed a high concentration of saturated fatty acids (mainly n-hexadecanoic acid) and terpenoids (mainly 4-(hydroxy-ethyl)-γ-butanolactone). CONCLUSION: The cytotoxic activity and selectivity of the non-polar extracts of E. chilensis for the MCF-7 and PC-3 cell lines could be related to the terpenic compounds and fatty acids of the extracts or to the synergistic effect of all of the compounds in the extracts. These non-polar extracts can be used for the development of new drugs against breast and prostate cancer.

Synthesis and Antiproliferative Activity of New Cyclodiprenyl Phenols against Select Cancer Cell Lines.

Six new cyclodiprenyl phenols were synthesized by direct coupling of perillyl alcohol and the appropriate phenol. Their structures were established by IR, HRMS and mainly NMR. Three human cancer cell lines-breast (MCF-7), prostate (PC-3) and colon (HT-29)-were used in antiproliferative assays, with daunorubicin and dunnione as positive controls. Results described in the article suggest that dihydroxylated compounds 2⁻4 and monohydroxylated compound 5 display selectivity against cancer cell lines, cytotoxicity, apoptosis induction, and mitochondrial membrane impairment capacity. Compound 2 was identified as the most effective of the series by displaying against all cancer cell lines a cytotoxicity close to dunnione antineoplastic agent, suggesting that the cyclodiprenyl phenols from perillyl alcohol deserve more extensive investigation of their potential medicinal applications.

Structure-Activity Relationship of Dialkoxychalcones to Combat Fish Pathogen Saprolegnia australis.

To investigate the anti-Saprolegnia activities of chalconic compounds, nine dialkoxychalcones 2⁻10, along with their key building block 2',4'-dihydroxychalcone 1, were evaluated for their potential oomycide activities against Saprolegnia australis strains. The synthesis afforded a series of O-alkylated derivatives with typical chalcone skeletons. Compounds 4⁻10 were reported for the first time. Interestingly, analogue 8 with the new scaffold demonstrated remarkable in vitro growth-inhibitory activities against Saprolegnia strains, displaying greater anti-oomycete potency than the standard drugs used in the assay, namely fluconazole and bronopol. In contrast, a dramatic loss of activity was observed for O-alkylated derivatives 2, 3, 6, and 7. These findings have highlighted the therapeutic potential of the natural compound 1 scaffold to be exploitable as a drug lead with specific activity against various Saprolegnia strains.

(-)-Shikimic Acid as a Chiral Building Block for the Synthesis of New Cytotoxic 6-Aza-Analogues of Angucyclinones.

We describe the syntheses of nine new angucyclinone 6-aza-analogues, achieved through a hetero Diels-Alder reaction between the shikimic acid derivative-azadiene 13, with different naphthoquinones. The cytotoxic activity of the new synthesized compounds and five angucyclinones, previously reported, was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and one non-tumoral cell line, human colon epithelial cells (CCD841 CoN). Our results showed that most 6-azadiene derivatives exhibited significant cytotoxic activities, which was demonstrated by their IC50 values (less than 10 µM), especially for the most sensitive cells, PC-3 and HT-29. From a chemical point of view, depending on the protected group of ring A and the pattern of substitution on ring D, cytotoxicity elicited these compounds, in terms of their potency and selectivity. Therefore, according to these chemical features, the most promising agents for every cancer cell line were 7a, 17, and 19c for PC-3 cells; 7a, 17, and 20 for HT-29 cells, and 19a for MCF-7 cells.

Hemi-Synthesis and Anti-Oomycete Activity of Analogues of Isocordoin.

An efficient synthesis of a series of 4'-oxyalkyl-isocordoin analogues (2-8) is reported for the first time. Their structures were confirmed by ¹H-NMR, 13C-NMR, and HRMS. Their anti-oomycete activity was evaluated by mycelium and spores inhibition assay against two selected pathogenic oomycetes strains: Saprolegnia parasitica and Saprolegnia australis. The entire series of isocordoin derivatives (except compound 7) showed high inhibitory activity against these oomycete strains. Among them, compound 2 exhibited strong activity, with minimum inhibitory concentration (MIC) and minimum oomyceticidal concentration (MOC) values of 50 µg/mL and 75 µg/mL, respectively. The results showed that 4'-oxyalkylated analogues of isocordoin could be potential anti-oomycete agents.

Synthesis and Evaluation of Novel Oxyalkylated Derivatives of 2',4'-Dihydroxychalcone as Anti-Oomycete Agents against Bronopol Resistant Strains of Saprolegnia sp.

A series of novel oxyalkylchalcones substituted with alkyl groups were designed and synthesized, and the antioomycete activity of the series was evaluated in vitro against Saprolegnia strains. All tested O-alkylchalcones were synthesized by means of nucleophilic substitution from the natural compound 2',4'-dihydroxychalcone (1) and the respective alkyl bromide. The natural chalcone (1) and 10 synthetic oxyalkylchalcones (2-11) were tested against Saprolegnia parasitica and Saprolegnia australis. Among synthetic analogs, 2-hydroxy,4-farnesyloxychalcone (11) showed the most potent activity against Saprolegnia sp., with MIC and MOC values of 125 µg/mL (similar to bronopol at 150 µg/mL) and 175 µg/mL, respectively; however, 2',4'-dihydroxychalcone (1) was the strongest and most active molecule, with MIC and MOC values of 6.25 µg/mL and 12.5 µg/mL.

Psoralea glandulosa as a potential source of anticancer agents for melanoma treatment.

With the aim of identifying novel agents with antigrowth and pro-apoptotic activity on melanoma cancer, the present study was undertaken to investigate the biological activity of the resinous exudate of aerial parts from Psoralea glandulosa, and its active components (bakuchiol (1), 3-hydroxy-bakuchiol (2) and 12-hydroxy-iso-bakuchiol (3)) against melanoma cells (A2058). In addition, the effect in cancer cells of bakuchiol acetate (4), a semi-synthetic derivative of bakuchiol, was examined. The results obtained show that the resinous exudate inhibited the growth of cancer cells with IC50 value of 10.5 µg/mL after 48 h of treatment, while, for pure compounds, the most active was the semi-synthetic compound 4. Our data also demonstrate that resin is able to induce apoptotic cell death, which could be related to an overall action of the meroterpenes present. In addition, our data seem to indicate that the apoptosis correlated to the tested products appears, at least in part, to be associated with an increase of reactive oxygen species (ROS) production. In summary, our study provides the first evidence that P. glandulosa may be considered a source of useful molecules in the development of analogues with more potent efficacy against melanoma cells.

Chemical Characterization and Anti-Oomycete Activity of Laureliopsis philippianna Essential Oils against Saprolegnia parasitica and S. australis.

Laureliopsis philippiana (Looser) R. Schodde (Monimiaceae) is a native tree widespread in the forest areas in the south of Chile and Argentina, known for its medicinal properties and excellent wood. The aim of this study was to evaluate the chemical composition of L. philippiana leaf and bark essential oils (EOs) using gas chromatography-mass spectrometry (GC-MS), and to quantify its anti-oomycete activity, specifically against Saprolegnia parasitica and S. australis. Only six components were identified in leaf EO, 96.92% of which are phenylpropanoids and 3.08% are terpenes. As for bark EO, 29 components were identified, representing 67.61% for phenylpropanoids and 32.39% for terpenes. Leaf EO was characterized mainly by safrole (96.92%) and ß-phellandrene (1.80%). Bark EO was characterized mainly by isosafrole (30.07%), safrole (24.41%), eucalyptol (13.89%), methyleugenol (7.12%), and eugenol (6.01%). Bark EO has the most promising anti-Saprolegnia activity, with a minimum inhibition concentration (MIC) value of 30.0 µg/mL against mycelia growth and a minimum fungicidal concentration (MFC) value of 50.0 µg/mL against spores; for leaf EO, the MIC and MFC values are 100 and 125 µg/mL, respectively. These findings demonstrate that bark EO has potential to be developed as a remedy for the control of Saprolegnia spp. in aquaculture.

Study on the cytotoxic activity of drimane sesquiterpenes and nordrimane compounds against cancer cell lines.

Twelve drimanes, including polygodial (1), isopolygodial (2), drimenol (3), confertifolin (4), and isodrimenin (5), were obtained from natural sources. Semi-synthetic derivatives 6-12 were obtained from 1 and 2, and cytotoxic activity was evaluated in vitro against cancer cell lines (HT-29, MDA-MB231, DHF, MCF-7, PC-3, DU-145, and CoN). IC50 values were determined at concentrations of 12.5-100 µM of each compound for 72 h. In addition, it was found that polygodial (1), 8, and 12 induced changes in mitochondrial membrane permeability in CoN, MCF-7, and PC-3 cells.

Ethanolic Extract from Fruits of Pintoa chilensis, a Chilean Extremophile Plant. Assessment of Antioxidant Activity and In Vitro Cytotoxicity.

Pintoa chilensis is a shrub with yellow flowers that reach up to two meters high, endemic of the Atacama Region in Chile. This species grows under special environmental conditions such as low altitude, arid areas, and directly sun-exposed habitats. In the present study, ethanolic extract was obtained from fruits of P. chilensis, and then partitioned in solvents of increasing polarity to obtain five fractions: hexane (HF), dichloromethane (DF), ethyl acetate (AF), and the residual water fraction (QF). The antioxidant activity of extracts was evaluated by using the DPPH, ABTS, and FRAP methods. The results show that the antioxidant capacity of P. chilensis is higher than that reported for other plants growing in similar environments. This effect is attributed to the highest content of flavonoids and total phenols found in P. chilensis. On the other hand, the cell viability of a breast cancer cell line (MCF-7) and a non-tumor cell line (MCF-10A) was assessed in the presence of different extract fractions. The results indicate that the hexane fraction (HF) exhibits the highest cytotoxicity on both cell lines (IC50 values equal to 35 and 45 µg/mL), whereas the dichloromethane fraction (DF) is the most selective one. The GC-MS analysis of the dichloromethane fraction (DF) shows the presence of fatty acids, sugars, and polyols as major components.