Protein-coding gene interaction network prediction of bioactive plant compound action against SARS-CoV-2: a novel hypothesis using bioinformatics analysis.

This study aimed to verify the action of bioactive compounds from Brazilian plants on the leader genes involved in the SARS-CoV-2 pathway. The main human genes involved were identified in GeneCards and UNIPROT platforms, and an interaction network between leader genes was established in the STRING database. To design chemo-biology interactome networks and elucidate the interplay between genes related to the disease and bioactive plant compounds, the metasearch engine STITCH 3.1 was used. The analysis revealed that SMAD3 and CASP3 genes are leader genes, suggesting that the mechanism of action of the virus on host cells is associated with the molecular effects of these genes. Furthermore, the bioactive plant compounds, such as ascorbate, benzoquinone, ellagic acid, and resveratrol was identified as a promising adjuvant for the treatment inhibiting CASP3-mediated apoptosis. Bioactive plant compounds were verified as the main pathways enriched with KEGG and related to viral infection, assessments/immune/infections, and cell proliferation, which are potentially used for respiratory viral infections. The best-ranked molecule docked in the CASP3 binding site was rutin, while the SMAD3 binding site was resveratrol. In conclusion, this work identified several bioactive compounds from Brazilian plants showing potential antiviral functions that can directly or indirectly inhibit the new coronavirus.

Development and Evaluation of a Low-cost Dairy Food Supplement with Mauritia Flexuosa (Buriti) to Combat Malnutrition: Translational Study in Mice and Institutionalized Elderly Woman.

AIMS: The present study aimed to develop and evaluate a new dairy by-product nutritional supplement with Buriti fruit to improve malnutrition in mice and elderly woman. BACKGROUND: Malnutrition is a prevalent problem in the elderly; therefore, oral dietary supplementation is an important strategy to reduce this health problem incidence. OBJECTIVE: The present study evaluated the effects of a low-cost food supplement, made from byproducts of the dairy and fruit industry in the Brazilian Cerrado (Buriti), on the nutritional status and on the recovery of the metabolic profile of malnourished animals and elderly women. METHODS: In the pre-clinical phase, Swiss mice were divided into six groups and subjected to malnutrition and renutrition. The clinical phase was carried out with 25 elderly women residing in a long-term institution, aged ≥ 65 years and with malnutrition or risk of malnutrition. RESULTS: The main results showed improvements in anthropometric parameters and an increase in serum albumin levels, in addition to lipid profile improvement in the preclinical phase and an increase in the red blood cells and hemoglobin in the clinical phase. CONCLUSION: The supplement based on Buriti was able to reverse malnutrition promoting improvements in anthropometric and biochemical parameters.

Effects of three γ-alkylidene-γ-lactams on the formation of multispecies biofilms.

This study evaluated the inhibitory effects of lactams on Streptococcus mutans, Enterococcus faecalis, and Candida glabrata multispecies biofilm formation. γ-Alkylidene-γ-lactams 1, 2, and 3 [solubilized in 3.5% dimethyl sulfoxide (DMSO)] were tested. Glass coverslips were conditioned with either the lactams or 3.5% DMSO (control) for 1 h, inoculated with microbial cultures, and incubated for 48 h. To assess the effect of the lactams on biofilm formation, the following parameters were determined: the biofilm biomass (by both crystal violet staining and protein determination); the amount of insoluble polysaccharides of the extracellular matrix; and the number of viable and total cells [by both colony-forming unit counting and quantitative real-time PCR (qPCR)]. Data were analysed using one-way anova and post-hoc Tukey tests. Lactams 1, 2, and 3 promoted a statistically significant reduction in the amount of biofilm biomass, but only lactam 3 resulted in a statistically significant reduction in the number of attached viable E. faecalis. Both total protein content and the amount of extracellular polysaccharides decreased significantly. The effects of γ-alkylidene-γ-lactams 1, 2, and 3 on the inhibition of multispecies biofilm formation were evident by their ability to reduce the amount of protein and extracellular polysaccharides.

Chemical, microscopic, and microbiological analysis of a functionalized poly-ether-ether-ketone-embedding antibiofilm compounds.

Poly-ether-ether-ketone (PEEK) is currently introduced as an alternative material for orthopedic implants due to its biocompatibility and low elastic modulus compared to titanium. Also, a sulphonation treatment can functionalize PEEK to embed therapeutical substances. The objective of this work was to functionalize a PEEK film to incorporate novel lactam-based antibiofilms compounds. PEEK samples were functionalized by sulphuric acid treatment and then dissolved in dimethylsulfoxide, where lactams were added to be incorporated into the polymer. A dip-coating technique was used to synthesize a thin film on a glass-based substrate. The degree of sulfonation (DS) and the incorporation of lactams into sulphonated PEEK (sPEEK) were analyzed by Fourier transform infrared spectroscopy, nuclear magnetic resonance, thermogravimetric analysis (TGA), and scanning electron microscopy. A DS of 65% was obtained and TGA curves confirmed the presence of SO3 H and lactams in the sPEEK structure. The growth of Streptococcus mutans biofilm decreased on sPEEK surface containing lactams when compared to sPEEK free of lactams. That indicated the antibiofilm activity of those compounds was maintained after incorporation into sPEEK. Planktonic growth analysis showed no long distant effects of sPEEK containing lactams, indicating that no systemic effects should be expected upon clinical uses of medical devices produced with lactam-treated sPEEK. Results revealed that inclusion of lactams into sPEEK represents a good alternative for the production of biomaterials resistant to bacterial accumulation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3015-3020, 2016.

Rubrolides as model for the development of new lactones and their aza analogs as potential photosynthesis inhibitors.

Natural phytotoxins and their synthetic analogs are a potential source of new bioactive compounds for agriculture. Analogs of rubrolides, a class of γ-alkylidene-γ-lactones isolated from different ascidians, have been shown to interfere with the photosynthetic electron-transport chain, yet their activity needs to be improved. With this aim, ten 5-aryl-6-benzyl-4-bromopyridazin-3(2H)-ones were prepared in yields ranging from 44 to 88% by reaction of their correspondent γ-alkylidene-γ-lactones with NH2 NH2 . The structures of these rubrolide analogs were determined by (1) H- and (13) C-NMR, 2D-NMR (COSY and HETCOR), NOE difference, and MS techniques. These compounds were evaluated for their abilities of interfering with the light-driven reduction of ferricyanide by isolated spinach chloroplasts. Lactones with electron-withdrawing substituents in the para-position of the benzylidene ring were the most effective inhibitors. Characterization of the activity of 11b/11b' suggested a mechanism based on the interaction with the plastoquinone binding site of photosystem II. Addition of several compounds to the culture medium of a cyanobacterial model strain was found to inhibit algal growth. However, the relative effectiveness was not consistent with their activity in vitro, suggesting the occurrence of multiple targets and/or detoxyfication mechanisms. Indeed, the compounds showed differential effects on the heterotrophic growth of some crop species, Cucumis sativus and Sorghum bicolor. Pyridazin-3(2H)-ones 12e, 12i, and 12j, which have been found poorly active against the photosynthetic electron transport, were the most effective in inhibiting the growth of some weeds, Ipomoea grandifolia and Brachiaria decumbens, under greenhouse conditions.

Inhibition of Enterococcus faecalis biofilm formation by highly active lactones and lactams analogues of rubrolides.

Seven ß-aryl substituted γ-alkylidene-γ-lactones analogues of rubrolides were synthesized from mucobromic acid and converted through a lactamization with isobutylamine into their corresponding γ-hydroxy-γ-lactams (76-85%). These lactams were converted into (Z)- and (E)-γ-alkylidene-γ-lactams (23-45%). All compounds were fully characterized by IR, NMR ((1)H and (13)C), COSY and HETCOR bidimensional experiments, and NOE difference spectroscopy experiments when necessary. Evaluation of these three different classes of compounds against Enterococcus faecalis biofilm formation showed that all classes are active and the highest biofilm inhibition activity was caused by lactam 13f (IC50 = 0.76 µg/mL). Moreover, in almost all cases at least one of the lactams is more active than its correspondent γ-alkylidene-γ-lactone. The use of rubrolides as a lead structure has proven successful for the identification of new compounds displaying novel antibacterial activities, namely biofilm inhibition, which have the potential for the development of antimicrobial drugs targeted to inhibition of the initial stages of bacterial infections, rather than bacterial viability. Such drugs are less prompt to induce bacterial resistance, being therefore a more cost-effective investment for pharmaceutical research.

γ-Alkylidene-γ-lactones and isobutylpyrrol-2(5H)-ones analogues to rubrolides as inhibitors of biofilm formation by gram-positive and gram-negative bacteria.

Several molecules have been discovered that interfere with formation of bacterial biofilms, opening a new strategy for the development of more efficient treatments in case of antibiotic resistant bacteria. Amongst the most active compounds are some natural brominated furanones from marine algae Delisea pulchra that have proven to be able to control pathogenic biofilms. We have recently reported that some rubrolide analogues are able to inhibit biofilm formation of Enterococcus faecalis. In the present Letter we describe results of the biological evaluation of a small library of 28 compounds including brominated furanones and the corresponding lactams against biofilm formation of Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis and Streptococcus mutans. Our results showed that in general these compounds were more active against biofilms of S. epidermidis and P. aeruginosa, with little or no inhibition of planktonic bacterial growth. In some cases they were able to prevent biofilm formation of P. aeruginosa at concentrations as low as 0.6 µg/mL (1.3 µM, compound 3d) and 0.7 µg/mL (1.3 µM, 3f). Results also indicate that, in general, lactams are more active against biofilms than their precursors, thus designating this class of molecules as good candidates for the development of a new generation of antimicrobial drugs targeted to biofilm inhibition.

Synthesis and phytotoxic activity of ozonides.

The [4 + 3] cycloaddition of the proper furans with the oxyallyl cation, generated in situ from 2,4-dibromopentan-3-one, produced a series of 8-oxabicyclo [3.2.1]oct-6-en-3-ones. Exposure of the oxabicycles to ozone afforded the corresponding 8,9,10,11-tetraoxatricyclo[5.2.1.1 (2,6)]undecan-4-ones in variable yields (7-100%). The phytotoxic properties of these ozonides (or 1,2,4-trioxolanes) and their oxabicycle precursors were evaluated as the ability to interfere with the growth of Sorghum bicolor and Cucumis sativus seedlings. Among oxabicycles, the highest inhibitory activity was shown by compounds possessing a alpha,beta-unsaturated carbonyl moiety. A differential sensitivity of the two crops was evident with ozonides. The most active compounds were also tested against the weed species Ipomoea grandifolia and Brachiaria decumbens. To the best of our knowledge, this is the first article describing ozonides as potential herbicides.