RESUMO

Gaultheria pumila (Ericaceae) (known as Chaura or Mutilla) is a Chilean native small shrub that produces berry fruits consumed by local Mapuche people. In this study, the chemical fingerprinting and antioxidant, enzyme inhibition, and antiproliferative activities of the berries were investigated for the first time. Thirty-six metabolites were identified in the fruits by ultra-high performance liquid chromatography-photodiode array detection, hyphenated with Orbitrap mass spectrometry analysis (UHPLC-DAD-Orbitrap-MS). Metabolites, included anthocyanins, phenolic acids, flavonoids, iridoids, diterpenes, and fatty acids. Moderate inhibitory activities against acetylcholinesterase (7.7 ± 0.3 µg/mL), butyrylcholinesterase (34.5 ± 0.5 µg/mL), and tyrosinase (3.3 ± 0.2 µg/mL) enzymes were found. Moreover, selected major compounds were subjected to docking assays in light of their experimental inhibition. Results indicated that hydrogen bonding, π-π interaction, and a salt bridge interaction contributed significantly. Gaultheria pumila berries showed a total phenolic content of 189.2 ± 0.2 mg of gallic acid equivalents/g, total flavonoid content of 51.8 ± 0.1 mg quercetin equivalents/g, and total anthocyanin content of 47.3 ± 0.2 mg of cianydin-3-glucoside equivalents/g. Antioxidant activity was assessed using DPPH (92.8 ± 0.1 µg/mL), FRAP (134.1 ± 0.1 µmol Trolox equivalents/g), and ORAC (4251.6 ± 16.9 µmol Trolox equivalents/g) assays. Conversely, Gaultheria pumila showed a scarce antiproliferative potential against several solid human cancer cells. Our findings suggest that Gaultheria pumila berries have several bioactive metabolites with inhibitory effects against acetylcholinesterase, butyrylcholinesterase, and tyrosinase, and have the potential for use in food supplements.

RESUMO

Persicaria maculosa (Polygonaceae) (known as lady's thumb) is an annual morphologically variable weed that is widely distributed in Chile. The purpose of this study was to investigate the antifeedant potential of methanolic (MeOH), ethanolic (EtOH), and dichloromethane (DCM) extracts from the aerial parts of this plant collected in the Valparaíso and Curicó provinces (Chile) and relate this activity to the antioxidant capacity and the presence of phenolic compounds in the extracts. A phenolic profile based on HPLC-ESI-MS/MS allowed the identification of 26 phenolic compounds, most of them glycosyl derivatives of isorhamnetin, quercetin, and kaempferol. In addition, the total phenolic content (TP), total flavonoids (TF), and antioxidant activity measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion scavenging (O2-), ferric-reducing antioxidant power (FRAP), and cupric-reducing antioxidant capacity (CUPRAC) of the extracts are reported. The antifeedant potentials of the plant extracts were tested against Epilachna paenulata, Pseudaletia adultera, Macrosiphum euphorbiae, and Diaphorina citri insects for the first time. The activity against the aphid M. euphorbiae was significant for the DCM extracts of plants from Valparaíso and Curicó (settling % = 23% ± 4% and 23% ± 5%, respectively). The antifeedant activities against the beetle E. paenulata and the lepidoptera P. adultera were significant for Valparaíso extracts, especially when tested against E. Paenulata (IFP = 1.0 ± 0.0). Finally, the MeOH and EtOH extracts from Valparaíso plants reduced the diet consumption of the psilid D. citri (p < 0.05). The results showed that P. maculosa is a good source of flavonoids with some antioxidant capacities and has potential interest as botanical eco-friendly alternative with deterrent activity.

Assuntos

RESUMO

Many protein kinase (PK) inhibitors have been reported in recent years, but only a few have been approved for clinical use. The understanding of the available molecular information using computational tools is an alternative to contribute to this process. With this in mind, we studied the binding modes of 77 maleimide derivates inside the PK glycogen synthase kinase 3 beta (GSK3ß) using docking experiments. We found that the orientations that these compounds adopt inside GSK3ß binding site prioritize the formation of hydrogen bond (HB) interactions between the maleimide group and the residues at the hinge region (residues Val135 and Asp133), and adopt propeller-like conformations (where the maleimide is the propeller axis and the heterocyclic substituents are two slanted blades). In addition, quantitative structure-activity relationship (QSAR) models using CoMSIA methodology were constructed to explain the trend of the GSK3ß inhibitory activities for the studied compounds. We found a model to explain the structure-activity relationship of non-cyclic maleimide (NCM) derivatives (54 compounds). The best CoMSIA model (training set included 44 compounds) included steric, hydrophobic, and HB donor fields and had a good Q(2) value of 0.539. It also predicted adequately the most active compounds contained in the test set. Furthermore, the analysis of the plots of the steric CoMSIA field describes the elements involved in the differential potency of the inhibitors that can be considered for the selection of suitable inhibitors.

Assuntos

RESUMO

The binding modes of 42 oxadiazole derivates inside glycogen synthase kinase 3 beta (GSK3ß were determined using docking experiments; thus, the preferred active conformations of these inhibitors are proposed. We found that these compounds adopt a scorpion-shaped conformation and they accept a hydrogen bond (HB) from the residue Val135 of the GSK3ß ATP-binding site hinge region. In addition, quantitative structure-activity relationship (QSAR) models were constructed to explain the trend of the GSK3ß inhibitory activities for the studied compounds. In a first approach, three-dimensional (3D) vectors were calculated using docking conformations and, by using multiple-linear regression, we assessed that GETAWAY vectors were able to describe the reported biological activities. In other QSAR approach, SMILES-based optimal descriptors were calculated. The best model included three-SMILES elements SSSß leading to the identification of key molecular features that contribute to a high GSK3ß inhibitory activity.

Assuntos

RESUMO

A los extractos etanólico y etéreo de hojas y frutos de Ficus obtusifolia Kunth (Moraceae), se les evaluó la actividad antiparasitaria contra Toxocara canis y Toxocara catis, y la antimicrobiana, contra Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli y Proteus vulgaris. Asimismo, se les realizó tamización fitoquímica para determinar algunos metabolitos secundarios y se midió su toxicidad con Artemia salina. El extracto etanólico del fruto mostró mayor mortalidad para parásitos adultos in vivo y presentó mayor inhibición embrionaria en huevos de T. canis. Ningún extracto exhibió halo de inhibición en el agar Mueller-Hinton, lo cual indica que no hay actividad antimicrobiana. Se observó mayor toxicidad frente a la A. salina a las 24 horas, para el extracto etanólico de hojas y frutos.

The antiaparatsitic activity of ether and ethanol extract in Ficus obtusifolia Kunth (Moraceae) leaves and fruits was assessed against Toxocara canis and Toxocara catis and the antimicrobial activity against Staphylococcus aureus, Streptococcus pyogenes, E-coli and Proteus vulgaris. Likewise, phytochemical screening was conducted to determine some secondary metabolites, and their toxicity was measured with Arthemia saline. Ethanol fruit extract showed a better mortality rate for adult parasites in vivo and showed higher embryonic inhibition in eggs of T. canis. No extract showed an inhibition halo in the Mueller-Hinton agar, which indicates that there is no antimicrobial activity. Increased toxicity was observed in contact with Arthemia saline at 24 hours for the ethanol extract of leaves and fruit.

Assuntos