Highly Enantioselective Lewis Acid Catalyzed Conjugate Addition of Imidazo[1,2-a]pyridines to α,ß-Unsaturated 2-Acylimidazoles under Mild Conditions.

A highly enantioselective protocol for the conjugate addition of 2-arylimidazo[1,2-a]pyridines and other imidazo derivatives to α,ß-unsaturated 2-acylimidazoles is described. The method uses a previously reported chiral-at-metal rhodium catalyst and provides the corresponding adducts in yields of 25-98% with enantioselectivities up to er > 99:1. Additionally, the transformation proceeds under mild conditions using ethanol as the solvent at room temperature.

Antarctic fungi produce pigment with antimicrobial and antiparasitic activities.

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.

Diversity of fungal endophytes from mangrove plants of Santa Catarina Island, Brazil.

The mangrove ecosystem plays a crucial role in preserving the biodiversity of plants, animals, and microorganisms that are essential for materials cycles. However, the exploration of endophytic fungi isolated from mangroves, particulary in Santa Catarina (SC, Brazil), remains limited. Therefore, the purpose of this study was to assess the biodiversity of endophytic fungi found in Avicennia schaueriana, Laguncularia racemosa, Rhizophora mangle, and Spartina alterniflora from two mangroves on the Island of Santa Catarina: one impacted by anthropic action (Itacorubi mangrove) and the other environmentally preserved (Ratones mangrove). Samplings were carried out between January 2020 and May 2021. Fungi were isolated from leaves, stems, and roots, identified, and clustered into groups through morphological characteristics. Further, a representative strain of each group was identified through ITS1 sequencing. A total of 373 isolates were obtained from plant tissues, of which 96 and 277 isolates were obtained from Itacorubi and Ratones mangroves, respectively. Molecular identification showed that the endophytic fungal community comprised at least 19 genera. The data on fungal community diversity revealed comparable diversity indices for genera in both mangroves. However, we observed differences in the total frequency of fungal genera between impacted (27.38%) and non-impacted (72.62%) mangroves. These findings suggest that anthropic activities in and around the Santa Catarina mangroves have had negative impact on the frequency of endophytic fungi. This emphasizes the reinforcing the significance of preserving these environments to ensure the maintenance of fungal community diversity.

Unveiling chemical responses in the kombucha-based fermentation of black tea, banana flower, and grape juice: LC-ESIMS, GNPS, MS-DIAL, and MS-FINDER-assisted chemical characterization.

The lack of studies evaluating the chemical responses of kombucha microorganisms when exposed to plants is notable in the literature. Therefore, this work investigates the chemical behaviour of 7-, 14- and 21 day-fermentation of kombucha derived from three extracts obtained from banana inflorescence, black tea, and grape juice. After the acquisition of UPLC-ESI-MS data, GNPS molecular networking, MS-Dial, and MS-Finder were used to chemically characterize the samples. The microbial chemical responses were enzymatic hydrolysis, oxidation, and biosynthesis. The biosynthesis was different among the kombucha samples. In fermented black tea, gallic and dihydrosinapic acids were found as hydrolysis products alongside a sugar-derived product namely 7-(α-D-glucopyranosyloxy)-2,3,4,5,6-pentahydroxyheptanoic acid. The sphingolipids, safingol and cedefingol alongside capryloyl glycine and palmitoyl proline were identified. In fermented grapes, sugar degradation and chemical transformation products were detected together with three cell membrane hopanoids characterized as hydroxybacteriohopanetetrol cyclitol ether, (Δ6 or Δ11)-hydroxybacteriohopanetetrol cyclitol ether, and methyl (Δ6 or Δ11)-hydroxybacteriohopanetetrol cyclitol. The fermented banana blossom showed the presence of methyl (Δ6 or Δ11)-hydroxybacteriohopanetetrol cyclitol together with sphingofungin B, sphinganine and other fatty acid derivatives. Parts of these samples were tested for their inhibition against α-glucosidase and their antioxidant effects. Except for the 14-day fermented extracts, other black tea extracts showed significant inhibition of α-glucosidase ranging from 42.5 to 42.8%. A 14-day fermented extract of the banana blossom infusion showed an inhibition of 29.1%, while grape samples were less active than acarbose. The 21-day fermented black tea extract showed moderate antioxidant properties on a DPPH-based model with an EC50 of 5.29 ± 0.10 µg mL-1, while the other extracts were weakly active (EC50 between 80.76 and 168.12 µg mL-1).

Evaluation of the anti-inflammatory effect of 1,4-dihydropyridine derivatives.

INTRODUCTION: Inflammation is a physiological event that protects the organism against different factors that lead to loss of tissue homeostasis. Dihydropyridine (DHP) derivatives are heterocyclic compounds known for their different biological activities, including anti-inflammatory activities. OBJECTIVE: To evaluate the anti-inflammatory activity of 1,4-dihydropyridine (1,4-DHP) derivatives using anti-inflammatory models in vitro, in RAW264.7 cells induced by lipopolysaccharide (LPS) and in vivo using the acute lung injury (ALI) model in mice. RESULTS: Fifteen compounds derived from 1,4-DHP were tested in RAW264.7 cells for their cytotoxic effect and cell viability. Thereafter, only the six compounds that showed the highest cell viability were tested for the production or inhibition of the pro-inflammatory cytokine interleukin 6 (IL-6). The best compound (compound 4) was tested for its anti-inflammatory effects in vitro and in vivo, showing inhibition of nitric oxide (NO), pro-inflammatory cytokines, increased phagocytic activity, and an increase in IL-10 in vitro. In in vivo tests, compound 4 also reduces the levels of NO, myeloperoxidase (MPO) activity, leukocyte migration, and exudation, as well as reducing the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 and preventing the loss in the lung architecture. CONCLUSION: This compound showed important anti-inflammatory activity, with a significant ability to reduce the production of pro-inflammatory mediators and increase the phagocytic activity of macrophages and anti-inflammatory mediator secretion (IL-10). These findings led us to hypothesize that this compound can repolarize the macrophage response to an anti-inflammatory profile (M2). Moreover, it was also able to maintain its anti-inflammatory activity in vivo experiments.

Inhibitory effects against SARSCoV-2 main protease (Mpro) of biflavonoids and benzophenones from the fruit of Platonia insignis.

The SARS-CoV-2 mutation and the limitation of the approved drug against COVID-19 are still a challenge in many country healthcare systems and need to be affronted despite the set of vaccines to prevent this viral infection. To contribute to the identification of new antiviral agents, the present study focused on natural products from an edible fruit with potential inhibitory effects against the SARS-CoV-2 main protease (Mpro). First, LC-ESIMS analysis of Platonia insignis fruits was performed and showed the presence of biflavonoids and benzophenones in the seed and pulp, respectively. Then, maceration and chromatographic purification led to the identification of two triglycerides (1 and 2) alongside chamaejasmine (3) and volkensiflavone (4) from the seed and isogarcinol (5) and cycloxanthochymol (6), from the pulp. Compounds 1-6 after evaluating their inhibitory against Mpro, displayed from no to significant activity. Compound 5 was the most potent with an IC50 value of 0.72 µM and was more active than the positive control, Ebselen (IC50 of 3.4 µM). It displayed weak and no cytotoxicity against THP-1 (CC50 of 116.2 µM) and Vero cell lines, respectively. Other active compounds showed no cytotoxicity against THP-1. and Vero cell lines. Molecular docking studies revealed interactions in the catalytic pocket between compound 5 and amino acid residues that composed the catalytic dyads (His 41 and Cyst 145).

Amazonian medicinal plants efficiently inactivate Herpes and Chikungunya viruses.

The Amazonian species investigated in this research are commonly utilized for their anti-inflammatory properties and their potential against various diseases. However, there is a lack of scientifically supported information validating their biological activities. In this study, a total of seventeen ethanolic or aqueous extracts derived from eight Amazonian medicinal plants were evaluated for their activity against Herpes Simplex type 1 (HSV-1) and Chikungunya viruses (CHIKV). Cytotoxicity was assessed using the sulforhodamine B method, and the antiviral potential was determined through a plaque number reduction assay. Virucidal tests were conducted according to EN 14476 standards for the most potent extracts. Additionally, the chemical composition of the most active extracts was investigated. Notably, the LMLE10, LMBA11, MEBE13, and VABE17 extracts exhibited significant activity against CHIKV and the non-acyclovir-resistant strain of HSV-1 (KOS) (SI > 9). The MEBE13 extract demonstrated unique inhibition against the acyclovir-resistant strain of HSV-1 (29-R). Virucidal assays indicated a higher level of virucidal activity compared to their antiviral activity. Moreover, the virucidal capacity of the most active extracts was sustained when tested in the presence of protein solutions against HSV-1 (KOS). In the application of EN 14476 against HSV-1 (KOS), the LMBA11 extract achieved a 99.9% inhibition rate, while the VABE17 extract reached a 90% inhibition rate. This study contributes to the understanding of medicinal species native to the Brazilian Amazon, revealing their potential in combating viral infections that have plagued humanity for centuries (HSV-1) or currently lack specific therapeutic interventions (CHIKV).

GC-MS comparison of fatty acids profile of oils extracted from viscera of Tainha (Mugil liza) and Tambaqui (Colossoma macropomum).

The commercial activity of the grey mullet (known as Tainha: TAI) and Tambaqui (TAM) generates tons of waste that can be turned into valuable resources. Therefore, this work aimed to chemically characterize and quantify the fatty acids profiles of the two fishes. GCMS quantification was performed by using calibration curves built from a standard that contains 19 FAME. The analysis revealed that visceral wastes from both fishes contain 16 fatty acids (FA) consisting of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA). However, their compositions were different as FA side chains in TAI and TAM contain 12 to 20 and 13 to 22 carbon atoms, respectively. Also, the SFA amount in TAI was greater than in TAM. On the other hand, TAM is richer in MUFA and PUFA compared to TAI. Both have similar chemical compositions of ω-3 and ω-6 in PUFA and ω-5, ω-7, and ω-9 in MUFA.

Bioactivity Screening and Chemical Characterization of Biocompound from Endophytic Neofusicoccum parvum and Buergenerula spartinae Isolated from Mangrove Ecosystem.

The discovery of biomolecules has been the subject of extensive research for several years due to their potential to combat harmful pathogens that can lead to environmental contamination and infections in both humans and animals. This study aimed to identify the chemical profile of endophytic fungi, namely Neofusicoccum parvum and Buergenerula spartinae, which were isolated from Avecinnia schaueriana and Laguncularia racemosa. We identified several HPLC-MS compounds, including Ethylidene-3,39-biplumbagin, Pestauvicolactone A, Phenylalanine, 2-Isopropylmalic acid, Fusaproliferin, Sespendole, Ansellone, Calanone derivative, Terpestacin, and others. Solid-state fermentation was conducted for 14-21 days, and methanol and dichloromethane extraction were performed to obtain a crude extract. The results of our cytotoxicity assay revealed a CC50 value > 500 µg/mL, while the virucide, Trypanosoma, leishmania, and yeast assay demonstrated no inhibition. Nevertheless, the bacteriostatic assay showed a 98% reduction in Listeria monocytogenes and Escherichia coli. Our findings suggest that these endophytic fungi species with distinct chemical profiles represent a promising niche for further exploring new biomolecules.

The Genus Dacryodes Vahl.: Ethnobotany, Phytochemistry and Biological Activities.

Dacryodes Vahl. species, belonging to the Burseraceae family, are widely used in traditional medicine in tropical regions to treat a range of ailments including malaria, wounds, tonsillitis, and ringworms. This review discusses the distribution, ethnobotanical uses, phytochemistry, and bioactivities of Dacryodes species. The intent is to spur future research into isolating and identifying key active principles, secondary metabolites, and crude extracts, and evaluating their pharmacological and toxicological effects, as well as the mechanism of actions to understand their medicinal benefits. A systematic review of scientific electronic databases from 1963 to 2022 including Scifinder, Scopus, Pubmed, Springer Link, ResearchGate, Ethnobotany Research and Applications, Google Scholar, and ScienceDirect was conducted with a focus on Dacryodes edulis (G.Don) H.J. Lam and Dacryodes rostrata (Blume) H.J. Lam. Pharmacological data revealed that D. edulis isolates contain secondary metabolites and other phytochemical groups belonging to the terpenoids class with anti-microbial, anticancer, antidiabetic, antiinflammatory and hepatoprotective activities, highlighting its pharmacological potential in the therapy or management of diverse cancers, cardiovascular, and neurological diseases. Thus, phytochemicals and standardized extracts from D. edulis could offer safer and cost-effective chemopreventive and chemotherapeutic health benefits/regimen, or as alternative therapeutic remedy for several human diseases. Nevertheless, the therapeutic potential of most of the plants in the genus have not been exhaustively explored with regard to phytochemistry and pharmacology, but mostly complementary approaches lacking rigorous, scientific research-based knowledge. Therefore, the therapeutic potentials of the Dacryodes genus remain largely untapped, and comprehensive research is necessary to fully harness their medicinal properties.

Inhibitory effects of 190 compounds against SARS-CoV-2 Mpr o protein: Molecular docking interactions.

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.

Studies of Cytotoxicity Effects, SARS-CoV-2 Main Protease Inhibition, and in Silico Interactions of Synthetic Chalcones.

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.

Semisynthetic Sesquiterpene Lactones Generated by the Sensibility of Glaucolide B to Lewis and Brønsted-Lowry Acids and Bases: Cytotoxicity and Anti-Inflammatory Activities.

Sesquiterpene lactone (SL) subtypes including hirsutinolide and cadinanolide have a controversial genesis. Metabolites of these classes are either described as natural products or as artifacts produced via the influence of solvents, chromatographic mobile phases, and adsorbents used in phytochemical studies. Based on this divergence, and to better understand the sensibility of these metabolites, different pH conditions were used to prepare semisynthetic SLs and evaluate the anti-inflammatory and antiproliferative activities. Therefore, glaucolide B (1) was treated with various Brønsted-Lowry and Lewis acids and bases-the same approach was applied to some of its derivatives-allowing us to obtain 14 semisynthetic SL derivatives, 10 of which are hereby reported for the first time. Hirsutinolide derivatives 7a (CC50 = 5.0 µM; SI = 2.5) and 7b (CC50 = 11.2 µM; SI = 2.5) and the germacranolide derivative 8a (CC50 = 3.1 µM; SI = 3.0) revealed significant cytotoxic activity and selectivity against human melanoma SK-MEL-28 cells when compared with that against non-tumoral HUVEC cells. Additionally, compounds 7a and 7c.1 showed strongly reduced interleukin-6 (IL-6) and nitrite (NOx) release in pre-treated M1 macrophages J774A.1 when stimulated with lipopolysaccharide. Despite the fact that hirsutinolide and cadinanolide SLs may be produced via plant metabolism, this study shows that acidic and alkaline extraction and solid-phase purification processes can promote their formation.

The Antinociceptive Effect of a Hydroalcoholic Extract of Polygala altomontana and Its Chemical Profile Using UPLC-ESI-QTOF-HR-MS.

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.

Characterization of Planktochlorella nurekis Extracts and Virucidal Activity against a Coronavirus Model, the Murine Coronavirus 3.

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.

Pyrazolines as potential anti-Alzheimer's agents: DFT, molecular docking, enzyme inhibition and pharmacokinetic studies.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized as the main dementia in the elderly. Eighteen pyrazolines were synthesized and evaluated for their inhibitory effects against acetylcholinesterase (AChE) in vitro. Possible interactions between pyrazolines and the enzyme were explored by in silico experiments. Compound 2B of the series was the most active pyrazoline with an IC50 value of 58 nM. Molecular docking studies revealed two important π-π interactions with residues Trp 286 and Tyr 341. A correlation between the HOMO-1 surface and AChE inhibition was observed. ADMET assays demonstrated a good profile for compound 2B. From the abovementioned findings, a new avenue of compound 2B analogues could be explored to develop anti-AD agents.

Evidence that the anti-inflammatory effect of 4-aryl-4H-chromenes is linked to macrophage repolarization.

The inflammatory response is a common feature of many pathological conditions, and there is urgent necessity for new substances that minimize the harmful effects of inflammation. Chromenes represent a class of compounds with multiple pharmacological actions that have already been described and may be potential candidates for studies of therapeutic action. This study aimed to test novel 4-aryl-4H-chromene-derived molecules in an in vitro model of inflammation using lipopolysaccharide (LPS)-induced Raw 264.7 cells. Seven compounds derived from 4-aryl-4H-chromene were tested on Raw 264.7 cells to evaluate their cytotoxic effects. Next, the effect of the selected compounds on the pro-inflammatory mediators (tumor necrosis factor-alpha [TNF-α], monocyte chemoattractant protein-1 [MCP-1], interleukin [IL]-6) and on the anti-inflammatory mediators (IL-10 and IL-13) was analyzed, and finally, the effect of the compounds on macrophage apoptosis and expression of surface receptors (toll-like receptor 4 [TLR-4] and mannose) was evaluated. The results of this study demonstrated that changes in the molecular structure of 4-aryl-4H-chromene altered its cytotoxic profile. Therefore, derivatives that showed safe results were selected for further analyses (named compounds: 4-6). In these experiments, the compounds were able to decrease nitric oxide (NO) levels and production of MCP-1, IL-6, IL-10, and IL-13. Furthermore, these derivatives were effective in reducing macrophage apoptosis and the expression of surface receptors, as TLR-4/CD284. Moreover, compounds 5 and 6 also were effective in increasing mannose receptor (CD206) expression. The results indicate, for the first time to our knowledge, that the anti-inflammatory effect produced by chromenes is linked to macrophage repolarization (M1 to M2).

Effect of Aryl-Cyclohexanones and their Derivatives on Macrophage Polarization In Vitro.

Macrophages are critical in both tissue homeostasis and inflammation, and shifts in their polarization have been indicated as pivotal for the resolution of inflammatory processes. Inflammation is a complex and necessary component of the immune response to stimuli that are harmful to host homeostasis and is regulated by cellular and molecular events that remain a source of ongoing investigation. Among the compounds studied that have potential against autoimmune and inflammatory diseases, cannabinoids are currently highlighted. In this work, nineteen aryl-cyclohexanones diesters and their derivatives were synthesized based on the aryl-cyclohexane skeleton of phytocannabinoids, such as cannabidiol (CBD), and were evaluated for their anti-inflammatory and macrophage polarization potential. The results showed that Compound 4 inhibited the production of nitric oxide in RAW 264.7 macrophages. Furthermore, it reduced the levels of pro-inflammatory cytokines IL-12p70, TNF-α, IFN-γ, MCP-1, and IL-6 while, at the same time, was able to increase the production of anti-inflammatory cytokines IL-4, IL-10, and IL-13. Compound 4 also reduced macrophage apoptosis, increased the expression of the CD206 (mannose receptor) and at the same time, decreased the expression of CD284 (TLR-4 receptor) on the surface of these cells. Finally, it increased the phagocytic capacity and inhibited the phosphorylation of the p65 of NF-kß. In conclusion, Compound 4, identified as diethyl-4-hydroxy-2-(4-methoxyphenyl)-4-methyl-6-oxocyclohexane-1-3-dicarboxylate, showed significant anti-inflammatory effect, while demonstrating the ability to transform phenotypically macrophages from the M1 phenotype (pro-inflammatory) to the M2 phenotype (anti-inflammatory). This led us to hypothesize that the main mechanism of anti-inflammatory effect of this molecule is linked to its immune modulation capacity.

Anti-inflammatory and anti-aggregating effects of rangpur in the first trimester of growth: ultra-performance liquid chromatography-electrospray mass spectrometry profile and quantification of hesperidin.

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.

Natural Products with Tandem Anti-inflammatory, Immunomodulatory and Anti-SARS-CoV/2 Effects: A Drug Discovery Perspective against SARS-CoV-2.

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.