RESUMO

The present work reports the inhibitory effect of amides derived from gallic acid (gallamides) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), along with cytotoxicity evaluation and molecular docking studies. In addition to gallamides, other relevant compounds were also synthesized and evaluated against Mpro, making a total of 25 compounds. Eight compounds presented solubility issues during the inhibitory assay and one showed no inhibitory activity. Compounds 3a, 3b, and 3f showed the highest enzymatic inhibition with IC50 = 0.26 ± 0.19 µM, 0.80 ± 0.38 µM, and 2.87 ± 1.17 µM, respectively. Selenogallamide 6a exhibited IC50 values of 5.42 ± 2.89 µM and a comparison with its nonselenylated congener 3c shows that the insertion of the chalcogen moiety improved the inhibitory capacity of the compound by approximately 10 times. Regarding the cellular toxicity in THP-1 and Vero cells, compounds 3e and 3g, showed moderate cytotoxicity in Vero cells, while for THP-1 both were nontoxic, with CC50 > 150 µM. Derivative 3d showed moderate cytotoxicity against both cell lines, whereas 6d was moderatly toxic to THP-1. Other compounds analyzed do not induce substantial cellular toxicity at the concentrations tested. The molecular docking results for compounds 3a, 3b, and 3f show that hydrogen bonding interactions involving the hydroxyl groups (OH) of the gallate moiety are relevant, as well as the carbonyl group.

RESUMO

BACKGROUND: Multidrug-resistant bacteria in humans have prompted the search for alternative solutions derived from herbal medicines that can substitute antibiotics in livestock production. Thus, the goal of this study was to evaluate the phytogenic properties of Marrubium vulgare infusion (MVI) on weaned pigs. Thirty animals were randomly divided into five groups of six animals, each receiving a physiological solution, clenbuterol and the infusion extract at doses of 0.01 (MVI 1%), 0.1 (MVI 10%) and 0.2 (MVI 20%) mg kg-1 for 28 days. Biochemical parameters and the liquid chromatographic-electrospray ionization-mass spectrometric (LC-ESI-MS) chemical profiles of the infusion extract and animal serum were studied. RESULTS: The doses MVI 1 and 10% led to weight gain higher than the controls. No significant changes were noted in the biochemical parameters including erythrocytes, hemoglobin, hematocrit, mean corpuscular volume and others. Evaluation of enzymatic levels in blood revealed no significant changes. LC-ESI-MS data of MVI showed the presence of 34 secondary metabolites, and successive chromatographic purification of MVI yielded marrubiin and apigenin as major components. LC-ESI-MS data of animal serum showed the presence of a diterpene, a flavonoid and diverse cholic acid derivatives. CONCLUSION: Results indicated the doses MVI 1 and 10% promote weight gain with no significant alterations in blood biochemicals, and liver and kidney function. © 2024 Society of Chemical Industry.

RESUMO

Natural pigments have received special attention from the market and industry as they could overcome the harm to health and the environmental issues caused by synthetic pigments. These pigments are commonly extracted from a wide range of organisms, and when added to products they can alter/add new physical-chemical or biological properties to them. Fungi from extreme environments showed to be a promising source in the search for biomolecules with antimicrobial and antiparasitic potential. This study aimed to isolate fungi from Antarctic soils and screen them for pigment production with antimicrobial and antiparasitic potential, together with other previously isolated strains A total of 52 fungi were isolated from soils in front of the Collins Glacier (Southeast border). Also, 106 filamentous fungi previously isolated from the Collins Glacier (West border) were screened for extracellular pigment production. Five strains were able to produce extracellular pigments and were identified by ITS sequencing as Talaromyces cnidii, Pseudogymnoascus shaanxiensis and Pseudogymnoascus sp. All Pseudogymnoascus spp. (SC04.P3, SC3.P3, SC122.P3 and ACF093) extracts were able to inhibit S. aureus ATCC6538 and two (SC12.P3, SC32.P3) presented activity against Leishmania (L.) infantum, Leishmania amazonensis and Trypanossoma cruzii. Extracts compounds characterization by UPLC-ESI-QToF analysis confirmed the presence of molecules with biological activity such as: Asterric acid, Violaceol, Mollicellin, Psegynamide A, Diorcinol, Thailandolide A. In conclusion, this work showed the potential of Antartic fungal strains from Collins Glacier for bioactive molecules production with activity against Gram positive bacteria and parasitic protozoas.

Assuntos

RESUMO

COVID-19 has caused many deaths since the first outbreak in 2019. The burden on healthcare systems around the world has been reduced by the success of vaccines. However, population adherence and the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are still challenging tasks to be affronted. In addition, the newly approved drug presents some limitations in terms of side effects and drug interference, highlighting the importance of searching for new antiviral agents against SARS-CoV-2. The SARS-CoV-2 main protease (Mpr o ) represents a versatile target to search for new drug candidates due to its essential role in proteolytic activities responsible for the virus replication. In this work, a series of 190 compounds, composed of 27 natural ones and 163 synthetic compounds, were screened in vitro for their inhibitory effects against SARS-CoV-2 Mpro . Twenty-five compounds inhibited Mpro with inhibitory constant values (Ki ) between 23.2 and 241 µM. Among them, a thiosemicarbazone derivative was the most active compound. Molecular docking studies using Protein Data Bank ID 5RG1, 5RG2, and 5RG3 crystal structures of Mpro revealed important interactions identified as hydrophobic, hydrogen bonding and steric interactions with amino acid residues in the active site cavity. Overall, our findings indicate the described thiosemicarbazones as good candidates to be further explored to develop antiviral leads against SARS-CoV-2. Moreover, the studies showed the importance of careful evaluation of test results to detect and exclude false-positive findings.

Assuntos

RESUMO

SARS-CoV-2 main protease (Mpro ) plays an essential role in proteolysis cleavage that promotes coronavirus replication. Thus, attenuating the activity of this enzyme represents a strategy to develop antiviral agents. We report inhibitory effects against Mpro of 40 synthetic chalcones, and cytotoxicity activities, hemolysis, and in silico interactions of active compounds. Seven of them bearing a (E)-3-(furan-2-yl)-1-arylprop-2-en-1-one skeleton (10, 28, and 35-39) showed enzyme inhibition with IC50 ranging from 13.76 and 36.13 µM. Except for 35 and 36, other active compounds were not cytotoxic up to 150 µM against THP-1 and Vero cell lines. Compounds 10, and 35-39 showed no hemolysis while 28 was weakly hemotoxic at 150 µM. Moreover, molecular docking showed interactions between compound 10 and Mpro (PDBID 5RG2 and 5RG3) with proximity to cys145 and His41, suggesting a covalent binding. Products of the reaction between chalcones and cyclohexanethiol indicated that this binding could be a Michael addition type.

Assuntos

RESUMO

The hydroalcoholic extract of Polygala altomontana (30, 100, and 300 mg/kg, i.g.) showed a dose-dependent antinociceptive action during the inflammatory phase of the formalin test. In addition, the preparation (30 and 300 mg/kg, i.g.) showed anti-hyperalgesic action when tested on a mechanical nociception model. UPLC-ESI-QTOF-MS data indicated the active extract contained phenylpropanoid sucrose esters, glycosylated quercetin derivatives, styrylpyrones, and coumarins. Some identified compounds, including styrylpyrones and coumarins, have previously demonstrated antinociceptive action. The results also show that P. altomontana shows potential for developing pain-relieving herbal remedies and drugs.

Assuntos

RESUMO

Certain members of the Coronaviridae family have emerged as zoonotic agents and have recently caused severe respiratory diseases in humans and animals, such as SARS, MERS, and, more recently, COVID-19. Antivirals (drugs and antiseptics) capable of controlling viruses at the site of infection are scarce. Microalgae from the Chlorellaceae family are sources of bioactive compounds with antioxidant, antiviral, and antitumor activity. In the present study, we aimed to evaluate various extracts from Planktochlorella nurekis in vitro against murine coronavirus-3 (MHV-3), which is an essential human coronavirus surrogate for laboratory assays. Methanol, hexane, and dichloromethane extracts of P. nurekis were tested in cells infected with MHV-3, and characterized by UV-vis spectrophotometry, nuclear magnetic resonance (NMR) spectroscopy, ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), and the application of chemometrics through principal component analysis (PCA). All the extracts were highly efficient against MHV-3 (more than a 6 Log unit reduction), regardless of the solvent used or the concentration of the extract, but the dichloromethane extract was the most effective. Chemical characterization by spectrophotometry and NMR, with the aid of statistical analysis, showed that polyphenols, carbohydrates, and isoprene derivatives, such as terpenes and carotenoids have a more significant impact on the virucidal potential. Compounds identified by UPLC-MS were mainly lipids and only found in the dichloromethane extract. These results open new biotechnological possibilities to explore the biomass of P. nurekis; it is a natural extract and shows low cytotoxicity and an excellent antiviral effect, with low production costs, highlighting a promising potential for development and implementation of therapies against coronaviruses, such as SARS-CoV-2.

Assuntos

RESUMO

BACKGROUND: Citrus fruits are a rich source of valuable molecules, and their industrial processing produces bagasses, little explored to generate important by-products. These Citrus residues, including seeds and peels, also contain numerous pharmacologically important substances. To reduce the impact of these Citrus by-products, young, harvested fruits could be used as a functional supplemental food while another part is grown until maturity for industrial production. This study therefore aims to valorize rangpur (Citrus limonia) in the first 3 months of its growth by investigating and comparing its monthly chemical profiles using ultra-performance liquid chromatography-electrospray mass spectrometry (UPLC-ESI-MS) and its anti-inflammatory and antiplatelet activity. RESULTS: Extracts obtained from the fruits harvested in November, December, and January, 2017 and 2018 (L221117, L161217, and L160118) showed different UPLC-ESI-MS profiles. Twenty-five of the 26 detected metabolites were identified as cyclitol, pyrrolidine betaine, aryl propanoyl esters, chlorogenic acids, flavonoids, coumarins, and limonoids. Quantification studies indicated an increased concentration of hesperidin from the younger fruits to the older fruits of the series. L160118 reduced nitrogen oxide (NOx), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels more than other extracts. Their activity followed the same trends as the hesperidin concentration in each fruit. In contrast, the most promising antiplatelet activity was observed with the extracts from the two youngest fruits. This suggests combined effects of the chemical components found in these fruits' extracts. CONCLUSION: The extracts obtained from these young fruits showed considerable anti-inflammatory and antiplatelet activity. Overall, young rangpur could be used as raw material to produce functional foods without producing any waste. © 2022 Society of Chemical Industry.

Assuntos

RESUMO

Aiming to valorise the Atlantic Rainforest biodiversity in Santa Catarina, the chemical characterisation of the essential oils (EOs) from leaves of Vernonanthura montevidensis (Spreng.) H. Rob. is described for the first time. Fresh leaves collected in the year 2014 and 2015, were submitted to hydrodistillation to give pale blue EOs in yields of 0.21 and 0.19%, respectively. The EOs were characterised by GC-MS and GC-FID semi- and quantitative methods. The monoterpene ß-pinene was the major constituent in both samples reaching a maximum of 26.3%. The monoterpene α-pinene and the sesquiterpene ß-caryophyllene, were also among the major constituents in both samples. By means of the extracted ion chromatogram procedure, it was possible to detect chamazulene, which was associated with the pale blue colour of the essential oils. In the in vitro antimollicute assays, the essential oil was moderately active against Mycoplasma genitalium and M. pneumoniae with MIC values of 250 µg mL-1.

Assuntos

RESUMO

BACKGROUND: COVID-19 is still causing long-term health consequences, mass deaths, and collapsing healthcare systems around the world. There are no efficient drugs for its treatment. However, previous studies revealed that SARS-CoV-2 and SARS-CoV have 96% and 86.5% similarities in cysteine proteases (3CLpro) and papain-like protease (PLpro) sequences, respectively. This resemblance could be important in the search for drug candidates with antiviral effects against SARS-CoV-2. OBJECTIVE: This paper is a compilation of natural products that inhibit SARS-CoV 3CLpro and PLpro and, concomitantly, reduce inflammation and/or modulate the immune system as a perspective strategy for COVID-19 drug discovery. It also presents in silico studies performed on these selected natural products using SARS-CoV-2 3CLpro and PLpro as targets to propose a list of hit compounds. METHODS: The plant metabolites were selected in the literature based on their biological activities on SARS-CoV proteins, inflammatory mediators, and immune response. The consensus docking analysis was performed using four different packages. RESULTS: Seventy-nine compounds reported in the literature with inhibitory effects on SARS-CoV proteins were reported as anti-inflammatory agents. Fourteen of them showed immunomodulatory effects in previous studies. Five and six of these compounds showed significant in silico consensus as drug candidates that can inhibit PLpro and 3CLpro, respectively. Our findings corroborated recent results reported on anti-SARS-CoV-2 in the literature. CONCLUSION: This study revealed that amentoflavone, rubranoside B, savinin, psoralidin, hirsutenone, and papyriflavonol A are good drug candidates for the search of antibiotics against COVID-19.

Assuntos