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The use of hydrocolloids has greatly increased in recent years due to their pivotal role as functional ingredients. They can increase food consistency, control the microstructure that affects water absorption, alter texture and flavor, and improve the shelf life of baked products. In this work, we analyzed the effect of plant hemicelluloses such as Caesalpinia pulcherrima galactomannans and Tamarindus indica xyloglucans on the stability of frozen French bread dough. The amount of these additives used was optimized from an obtained central composite design- (CCD-) response surface methodology (RSM) of the alveograph parameters. Batches were characterized for moisture, water activity (aw), and texture using SEM, DSC, and TGA analyses when frozen for up to 60 days. Batches containing hemicelluloses showed better stability for aw over time. There was no difference between the texture parameters of the samples studied for 60 days. Both added hemicelluloses presented fewer fractures at 30 days and less wear at 60 days, in addition to better performance in the TGA analysis after less than 30 days of frozen storage. Batches containing only xyloglucans or galactomannans had a higher solidification peak temperature after 60 days. Both plant hemicelluloses reduced the damage caused by cold storage and improved stability for water activity. Also, dough preparations containing these additives showed better moisture retention, as well as less wear and tear and fewer fractures over their shelf life. Our evaluation suggests C. pulcherrima and T. indica are nonconventional sources of hydrocolloids that could be utilized in the bakery industry.

Abstract: Antibiotic resistance can be characterized, in biochemical terms, as an antibiotic’s inability to reach its bacterial target at a concentration that was previously effective. Microbial resistance to different agents can be intrinsic or acquired. Intrinsic resistance occurs due to inherent functional or structural characteristics of the bacteria, such as antibiotic-inactivating enzymes, nonspecific efflux pumps, and permeability barriers. On the other hand, bacteria can acquire resistance mechanisms via horizontal gene transfer in mobile genetic elements such as plasmids. Acquired resistance mechanisms include another category of efflux pumps with more specific substrates, which are plasmid-encoded. Efflux pumps are considered one of the main mechanisms of bacterial resistance to antibiotics and biocides, presenting themselves as integral membrane transporters. They are essential in both bacterial physiology and defense and are responsible for exporting structurally diverse substrates, falling into the following main families: ATP-binding cassette (ABC), multidrug and toxic compound extrusion (MATE), major facilitator superfamily (MFS), small multidrug resistance (SMR) and resistance-nodulation-cell division (RND). The Efflux pumps NorA and Tet(K) of the MFS family, MepA of the MATE family, and MsrA of the ABC family are some examples of specific efflux pumps that act in the extrusion of antibiotics. In this review, we address bacterial efflux pump inhibitors (EPIs), including 1,8-naphthyridine sulfonamide derivatives, given the pre-existing knowledge about the chemical characteristics that favor their biological activity. The modification and emergence of resistance to new EPIs justify further research on this theme, aiming to develop efficient compounds for clinical use.

Chagas disease is a leading public health problem.

aims: This work focuses on the antibacterial activity of chalcones against Staphylococcus aureus, which causes several diseases and is one of the main microorganisms with increasing resistance to conventional drugs. background: Studies with natural or synthetic products from chalcones have shown to be very promising due to their peculiar structure that allows different possibilities of reallocations that will define their diverse bioactivities in the creation of new substances. This creation is facilitated by the synthesis of substances in conjunction with the molecular study, which allows a considerable advance in research, reducing the number of in vitro tests. objective: This work focuses on the antibacterial activity of chalcones against Staphylococcus aureus, which causes several diseases and is one of the main microorganisms with increasing resistance to conventional drugs. method: Articles that studied antibacterial activity, efflux pump, or molecular docking were considered as complementary analysis in chalcones. From these data, molecular docking and ADMET of the first five chalcones were performed with the best activity found. result: The result of the antimicrobial activity against Staphylococcus aureus was confirmed through in silico study and pharmacokinetic data. conclusion: The results of the antimicrobial activity of the most active chalcones against Staphylococcus aureus was supported by in silico and the pharmacokinetic study which not only confirmed their potential to act against resistant strains but also established in future utility of chalcones as lead molecules or prototypes for the synthesis of potent new antimicrobial agents against Staphylococcus aureus. other: None

Chalcones have an open chain flavonoid structure that can be obtained from natural sources or by synthesis and are widely distributed in fruits, vegetables, and tea. They have a simple and easy to handle structure due to the α-β-unsaturated bridge responsible for most biological activities. The facility to synthesize chalcones combined with its efficient in combating serious bacterial infections make these compounds important agents in the fight against microorganisms. In this work, the chalcone (E)-1-(4-aminophenyl)-3-(4-nitrophenyl)prop-2-en-1-one (HDZPNB) was characterized by spectroscopy and electronic methods. In addition, microbiological tests were performed to investigate the modulator potential and efflux pump inhibition on S. aureus multi-resistant strains. The modulating effect of HDZPNB chalcone in association with the antibiotic norfloxacin, on the resistance of the S. aureus 1199 strain, resulted in increase the MIC. In addition, when HDZPNB was associated with ethidium bromide (EB), it caused an increase in the MIC value, thus not inhibiting the efflux pump. For the strain of S. aureus 1199B, carrying the NorA pump, the HDZPNB associated with norfloxacin showed no modulatory, and when the chalcone was used in association with EB, it had no inhibitory effect on the efflux pump. For the tested strain of S. aureus K2068, which carries the MepA pump, it can be observed that the chalcone together the antibiotic resulted in an increase the MIC. On the other hand, when chalcone was used in association with EB, it caused a decrease in bromide MIC, equal to the reduction caused by standard inhibitors. Thus, these results indicate that the HDZPNB could also act as an inhibitor of the S. aureus gene overexpressing pump MepA. The molecular docking reveals that chalcone has a good binding energies −7.9 for HDZPNB/MepA complexes, molecular dynamics simulations showed that Chalcone/MetA complexes showed good stability of the structure in an aqueous solution, and ADMET study showed that the chalcone has a good oral bioavailability, high passive permeability, low risk of efflux, low clearance rate and low toxic risk by ingestion. The microbiological tests show that the chalcone can be used as a possible inhibitor of the Mep A efflux pump. Communicated by Ramaswamy H. Sarma

The antibiotic potentiating activity against standard and multidrug-resistant Escherichia coli and Staphylococcus aureus bacterial strains of the natural compound 5”-O-α-L-raminopyranosyl-1’-β-D-glycopyranosyl-4’,6-dimethoxyflavone (pectolinarin) isolated from L. camara leaves was evaluated. Tests for antibacterial activity of the pure natural substance and analysis of the potentiation of antibacterial activity of pectolinarin associated with antibiotics were carried out against standard and multiresistant bacterial strains of Escherichia coli and Staphylococcus aureus by microdilution. Pectolinarin, when combined with the antibiotic gentamicin, showed synergism, potentiating growth inhibition against Gram-positive S. aureus strains. The pectolinarin flavonoid when combined with the gentamicin antibiotic potentiated its action Gram-positive S. aureus bacteria. Moreover, an antagonistic effect was observed when the pectolinarin was combined with the penicillin antibiotic against the multiresistant S. aureus 358 strain. This research suggests that pectolinarin is a compound with potential application as an antibacterial drug.

The use of the bacterial efflux pump mechanism to reduce the concentrations of antibiotics in the intracellular to the extracellular region is one of the main mechanisms by which bacteria acquire resistance to antibiotics. The present study aims to evaluate the antibacterial activity of the α,β-amyrin mixture isolated from Protium heptaphyllum against the multidrug-resistant strains of Escherichia coli 06 and Staphylococcus aureus 10, and to verify the inhibition of the efflux resistance mechanisms against the strains of S. aureus 1199B and K2068, carrying the NorA and MepA efflux pumps, respectively. The α,β-amyrin did not show clinically relevant direct bacterial activity. However, the α,β-amyrin when associated with the gentamicin antibiotic presented synergistic effect against the multidrug-resistant bacterial strain of S. aureus 10. In strains with efflux pumps, α,β-amyrin was able to inhibit the action of the efflux protein NorA against Ethidium Bromide. However, this inhibitory effect was not observed in the MepA efflux pump. In addition, when evaluating the effect of standard efflux pump inhibitors, clorptomazine and CCCP, α,β-amyrin showed a decrease in MIC, demonstrating the presence of the efflux mechanism through synergism. Docking studies indicate that α, β-amyrin have a higher affinity energy to MepA, and NorA than ciprofloxacin and norfloxacin. Also, α, β-amyrin bind to the same region of the binding site as these antibiotics. It was concluded that the α, β-amyrin has the potential to increase antibacterial activity with the association of antibiotics, together with the ability to be a strong candidate for an efflux pump inhibitor. Communicated by Ramaswamy H. Sarma

Chagas disease infects approximately seven million people worldwide. Benznidazole is effective only in the acute phase of the disease, with an average cure rate of 80% between acute and recent cases. Therefore, there is an urgent need to find new bioactive substances that can be effective against parasites without causing so many complications to the host. In this study, the triterpene 3β-6β-16β-trihydroxilup-20 (29)-ene (CLF-1) was isolated from Combretum leprosum, and its molecular structure was determined by NMR and infrared spectroscopy. The CLF-1 was also evaluated in vitro and in silico as potential trypanocidal agent against epimastigote and trypomastigote forms of Trypanosoma cruzi (Y strain). The CLF-1 demonstrated good results highlighted by lower IC50 (76.0 ± 8.72 µM, 75.1 ± 11.0 µM, and 70.3 ± 45.4 µM) for epimastigotes at 24, 48 and 72 h, and LC50 (71.6 ± 11.6 µM) for trypomastigotes forms. The molecular docking study shows that the CLF-1 was able to interact with important TcGAPDH residues, suggesting that this natural compound may preferentially exert its effect by compromising the glycolytic pathway in T. cruzi. The ADMET study together with the MTT results indicated that the CLF-1 is well-absorbed in the intestine and has low toxicity. Thus, this work adds new evidence that CLF-1 can potentially be used as a candidate for the development of new options for the treatment of Chagas disease. Communicated by Ramaswamy H. Sarma

Combretaceae are reported in the literature for presenting neuroprotective and anxiolytic effects in animal models. Combretum lanceolatum Pohl. has few scientific reports on its pharmacological eff...

Infectious diseases caused by multidrug-resistant microorganisms has increased in the last years. Piper species have been reported as a natural source of phytochemicals that can help in combating fungal and bacterial infections. This study had as objectives characterize the chemical composition of the essential oil from Piper caldense (EOPC), evaluate its potential antimicrobial activity, and investigate the synergistic effect with Norfloxacin against multidrug-resistant S. aureus overproducing efflux pumps, as well as, verify the EOPC ability to inhibit the Candida albicans filamentation. EOPC was extracted by hydrodistillation, and the chemical constituents were identified by gas chromatography, allowing the identification of 24 compounds (91.9%) classified as hydrocarbon sesquiterpenes (49.6%) and oxygenated sesquiterpenes (39.5%). Antimicrobial tests were performed using a 96-well plate microdilution method against C. albicans ATCC 10231, Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 standard strains, as well as against multidrug-resistant strains S. aureus SA1199B (overexpressing norA gene), S. aureus K2068 (overexpressing mepA gene) and S. aureus K4100 (overexpressing qacC gene). The oil showed activity against C. albicans ATCC 10231 (≥ 512 µg/mL) and was able to inhibit hyphae formation, an important mechanism of virulence of C. albicans. On the other hand, EOPC was inactive against all bacterial strains tested (≤ 1,024 µg mL). However, when combined with Norfloxacin at subinhibitory concentration EOPC reduced the Norfloxacin and Ethidium bromide MIC values against S. aureus strains SA1199B, K2068 and K4100. These results indicate that EOPC is a source of phytochemicals acting as NorA, MepA and QacC inhibitors.

A large number of infections are caused by Gram-positive and Gram-negative multi-resistant bacteria worldwide, adding up to a figure of around 700,000 deaths per year. The indiscriminate uses of antibiotics, as well as their misuse, resulted in the selection of bacteria resistant to known antibiotics, for which it has little or no treatment. In this way, the strategies to combat the resistance of microorganisms are extremely important and, essential oils of Croton species have been extensively studied for this purpose. The aim of this study was to carry the evaluation of antibacterial, antibiofilm, antioxidant activities, and spectroscopic investigation of essential oil from Croton piauhiensis (EOCp). The EOCp exhibited antimicrobial activity against Gram-positive and Gram-negative bacteria with required MICs ranging from 0.15 to 5% (v/v). In addition, the MBC of the EOCp for Staphylococcus aureus ATCC 25923 and ATCC 700698, were 0.15 and 1.25%, respectively. Moreover, the EOCp significantly reduced significantly the biofilm production and the number of viable cells from the biofilm of all bacterial strains tested. The antioxidant potential of the EOCp showed EC50 values ranging from 171.21 to 4623.83 μg/mL. The EOCp caused hemolysis (>45%) at the higher concentrations tested (1.25 to 5%), and minor hemolysis (17.6%) at a concentration of 0.07%. In addition, docking studies indicated d-limonene as a phytochemical with potential for antimicrobial activity. This study indicated that the EOCp may be a potential agent against infections caused by bacterial biofilms, and act as a protective agent against ROS and oxidative stress.

Anxiety and seizure are mental disorders commonly treated in the clinic with benzodiazepines (BZDs). However, long-term treatment with these drugs causes side effects such as decreased motor coordination, drowsiness, sedation, and, when used for a long time, leads to dependence and withdrawal syndromes. This study's objective was to evaluate the anxiolytic-like and anticonvulsant effect in adult zebrafish (Danio rerio) through GABAergic system of synthetic chalcone derived from cinnamaldehyde and natural acetophenone isolated from Croton anisodontus and their mechanisms of action via the Gabaergic system, using adult zebrafish. The animals were treated with chalcone (0.1 or 0.5 or 1.0 mg / kg; 20 µL; i.p;) and subjected to the open field test. The chalcone caused locomotor alteration when evaluated in the light & dark anxiolytic test. The lowest effective dose was chosen to assess possible involvement in the GABAA receptor. The chalcone showed anxiolytic and anticonvulsant effects in all doses in both tests. The chalcone presented anticonvulsant activity, a possible inhibitor of Carbonic Anhydrase and an anxiolytic effect dependent on the GABAergic system, coupling it in a different region from the diazepam inhibitor.

The sanitary emergency generated by the pandemic COVID-19, instigates the search for scientific strategies to mitigate the damage caused by the disease to different sectors of society. The disease caused by the coronavirus, SARS-CoV-2, reached 216 countries/territories, where about 20 million people were reported with the infection. Of these, more than 740,000 died. In view of the situation, strategies involving the development of new antiviral molecules are extremely important. The present work evaluated, through molecular docking assays, the interactions of 4′-acetamidechalcones with enzymatic and structural targets of SARS-CoV-2 and with the host’s ACE2, which is recognized by the virus, facilitating its entry into cells. Therefore, it was observed that, regarding the interactions of chalcones with Main protease (Mpro), the chalcone N-(4′[(2E)-3-(4-flurophenyl)-1-(phenyl)prop-2-en-1-one]) acetamide (PAAPF) has the potential for coupling in the same region as the natural inhibitor FJC through strong hydrogen bonding. The formation of two strong hydrogen bonds between N-(4[(2E)-3-(phenyl)-1-(phenyl)-prop-2-en-1-one]) acetamide (PAAB) and the NSP16-NSP10 heterodimer methyltransferase was also noted. N-(4[(2E)-3-(4-methoxyphenyl)-1-(phenyl)prop-2-en-1-one]) acetamide (PAAPM) and N-(4-[(2E)-3-(4-ethoxyphenyl)-1-(phenyl)prop-2-en-1-one]) acetamide (PAAPE) chalcones showed at least one strong intensity interaction of the SPIKE protein. N-(4[(2E)-3-(4-dimetilaminophenyl)-1-(phenyl)-prop-2-en-1-one]) acetamide (PAAPA) chalcone had a better affinity with ACE2, with strong hydrogen interactions. Together, our results suggest that 4′-acetamidechalcones inhibit the interaction of the virus with host cells through binding to ACE2 or SPIKE protein, probably generating a steric impediment. In addition, chalcones have an affinity for important enzymes in post-translational processes, interfering with viral replication., Graphical abstract Image 1, Highlights • Chalcones derivatives interacting with SARS-CoV-2 SPIKE protein. • Strong affinity with the ACE2 human host cells. • The 4′-acetamidechalcones can interfering with the virus replication.

Drugs used to manage type 2 diabetes mellitus cause adverse effects. Therefore, the search for new drugs as an alternative for the treatment of diabetes increases. The effect of triterpene 3β-6β-16β-trihydroxylup-20(29)-ene isolated from the leaves of C. leprosum (CLF-1) on sucrose-induced hyperglycemia in adult zebrafish (Danio rerio) was evaluated. Initially, adult zebrafish (n = 6/group) underwent hyperglycemia induction by sucrose at 83.25 mM/L for 7 days by immersion. The hyperglycemic groups were treated with CLF-1 (4, 20, and 40 mg/kg), metformin (200 mg/kg), and acarbose (300 mg/kg) for 4 days. The in silico interaction of CLF-1, metformin, and acarbose with the enzyme maltase-glucoamylase (CtMGAM) was investigated. CLF-1 reduced sucrose-induced hyperglycemia after 4 days of treatment, in addition to having better affinity energy with CtMGAM than metformin and acarbose. Thus, CLF-1 may be a new pharmacological alternative as a hypoglycemic agent for the treatment of diabetes.

Flavonoids belong to the extensive group of polyphenols and have several biological activities such as anti-inflammatory, anti-ulcer, anticancer, antiviral, antibacterial, and antispasmodic. These compounds can thus be explored as a tool against multidrug resistant bacteria, as nosocomial infections now constitute a major public health problem worldwide. We have carried out a structural characterization by nuclear magnetic resonance and FT-IR of fisetinidol, a flavonoid isolated from B. pentandra stems. In addition, this flavonoid was tested for antibacterial and modulatory activities, as well as inhibition of the NorA efflux pump. Fisetinidol has no intrinsic antibacterial activity. However, there is synergism in association with norfloxacin, with a two-fold decrease in MIC. When compared to chlorpromazine, a standard efflux pump inhibitor, a two-fold decrease in MIC was also verified when used against S. aureus SA-1199B, which over expresses the NorA gene encoding the NorA efflux protein. As such, it could become an alternative source to reverse the bacterial resistance if administered in association with antibiotics.

The action of anxiolytic compounds that act on selective serotonin receptors (SSRIs) have been scarcely evaluated. Serotonergic drugs have been shown to be effective in treating anxiety without presenting adverse effects as benzodiazepines. However, the anxiolytic effects take days to occur. This study aimed to evaluate the anxiolytic effect of the synthetic chalcone, 4’-[(2E) -3- (3-nitrophenyl) -1- (phenyl) prop-2-en-1-one] acetamide (PAAMNBA), and its possible mechanism of action in adult zebrafish (Danio rerio). PAAMNBA was synthesized with a yield of 51.3% and its chemical structure was determined by 1H and 13C NMR. Initially, PAAPMNBA was intraperitoneally administered to zebrafish (n = 6/group) at doses of 4, 12, or 40 mg/kg, and the animals were subsequently subjected to acute and open field toxicity tests. PAAMNBA was administered to the other groups (n = 6/group) for analyzing its effect in the light and dark test. The involvement of the serotonergic (5HT) system was also evaluated using 5-HTR 1, 5-HTR 2A/2C, and 5-HTR 3A/3B receptor antagonists, namely, pizotifeo, granizetron, and ciproeptadina, respectively. Molecular coupling was performed using the 5-HT1 receptor. PAAMNBA was found to be non-toxic, reduced the locomotor activity, and had an anxiolytic effect in adult zebrafish. The effect was reduced by pretreatment with pizotifene and was not reversed by treatment with granizetron and cyproeptadine. A previous in vivo molecular coupling study indicated that chalcones interact with the 5-HT1 receptor. The results suggested that the chalcone, PAAPMNBA, has anxiolytic activity, that is mediated by the serotonergic system via the 5-HT1 receptor. The interaction of PAAPMNBA with the 5-HT1 receptor was confirmed by molecular docking studies.

In this work, eight chalcones were synthesized from the 2-hydroxy-3,4,6trimethoxyacetophenone isolated from Croton anisodontus with benzaldehyde and its derivatives as well as evaluated its cytotoxic and antifungal activities. Chalcones were synthesized by the Claisen-Schimdt aldol condensation reaction in basic medium and identified by 1H and 13C NMR, IR and MS. The MTT assay was used to determine the cytotoxicity of all synthetized compounds against human cancer cell lines. The results showed that the % RCV varied from 19.43 ± 1.31 to 75.51 ± 1.84 %. The chalcone (E)-3-(4-fluorophenyl)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)prop-2-en-1-one demonstrated the strongest activity against HCT-116 cells (% RCV = 75.51 ± 1.84). The in vitro antifungal potential of the chalcones showed that chalcones (E)-3-(furan-2-yl)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)prop-2-en-1-one (MIC 0,625 mg/mL against C. albicans LABMIC 0105) and (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (MIC 0,312 mg/mL against C. albicans LABMIC 0107) were considered as chalcones of better fungal inhibition. The synergistic evaluation in vitro showed no synergistic effect for both chalcones and for kinetics of fungal death, only treatment with chalcone (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one against LABMIC 0107 was able to promote reduction of fungal cells between the periods of 4 to 8 h and 100% inhibition thereafter, resembling the mechanism of action of Amphotericin B.

A large number of infections are caused by multi-resistant bacteria worldwide, increasing to around 700,000 deaths per year. Because of that, many strategies are being developed to combat the resistance of microorganisms to drugs, and recently, chalcones have been studied for this purpose. Chalcones are known as α, β-unsaturated ketones, characterized by having the presence of two aromatic rings that are joined by a three-carbon chain. They are a class of compounds considered an exceptional model due to chemical simplicity and a wide variety of biological activities, including anticancer, anti-inflammatory, antioxidants, antimicrobials, anti-tuberculosis, anti-HIV, antimalarial, anti-allergic, antifungal, antibacterial, and antileishmaniasis. The objective of this work was to evaluate the antibacterial and antibiotic modifying activity of chalcone (2E)-1-(4'-aminophenyl)-3-(4-methoxyphenyl)-prop-2-en-1-one against the bacteria Staphylococcus aureus carrying a NorA and MepA efflux pump. The results showed that chalcone showed no toxicity on macrophage cells and was able to synergistically modulate the action of Norfloxacin and Ethidium Bromide against the bacteria Staphylococcus aureus 1199B and K2068, respectively. Furthermore, the theoretical physicochemical and pharmacokinetic properties of chalcone showed that it did not present a severe risk of toxicity such as genetic mutation or cardiotoxicity, constituting an excellent pharmacological active ingredient.

Diabetes mellitus is a chronic metabolic disorder that has been increasing drastically around the worldwide. It is important to emphasize that although many drugs are commercially available to treat diabetes, many of them have shown a number of adverse effects. Therefore, search for new antidiabetic agents is of great interest, and natural products, especially those obtained from plants sources, may be an alternative to available drugs. This study reports the in vivo and in silico evaluation of the hypoglycemic activity of fisetinidol. The conformational analysis confirmed that the fisetinidol compound possesses two valleys in the potential energy curve, showing a stable conformer on the global minimum of the PES defined by the dihedral angle θ (C6-C7-O-H) at 179.9°, whose energy is equal to zero. In addition, fisetinidol has shown promise in glycemic control and oxidative stress caused by hyperglycemia induced by high sucrose concentration, causing hypoglycemic and hepatoprotective effects in adult zebrafish. ADMET studies showed that fisetinidol has high passive permeability, low clearance and low toxic risk by ingestion, and computational studies demonstrated that fisetinidol complexes in the same region as metformin and α-acarbose, which constitutes a strong indication that fisetinidol has the same inhibitory mechanisms of α-acarbose and metformin. Communicated by Ramaswamy H. Sarma.

Dodecanoid acid, also known as lauric acid, is a molecular alloy phase change material, and as such, knowledge about its behavior under different temperatures is of utmost importance in order to de...

Anxiety is a mental disorder that affects 25% of patients with epilepsy, and treatments for anxiety and seizures involve the use of benzodiazepines, a class of drugs that have many adverse effects such as decreased motor coordination, drowsiness, and sedation. Thus, new types of drugs with minimal side effects are of immediate requirement. Chalcones comprise a class of compounds with important therapeutic potential and have recently been investigated for their potential as anxiolytic and anticonvulsant agents. Therefore, this study aimed to evaluate the anxiolytic and anticonvulsant effects of the synthetic chalcone (E)-3-(furan-2-yl)-1-(2hydroxy-3,4,6-trimethoxyphenyl)prop-2-en-1-one (FURCHAL) using adult zebrafish as an animal model. Anxiolytic potential was assessed using the light/dark test and the anticonvulsant effect in 3-stage pentylenetetrazol (PTZ)-induced seizure tests. The mechanisms of the anxiolytic effect were analyzed using γ-aminobutyric acid (GABA) and the serotoninergic system. The anxiolytic effect of FURCHAL was verified by a reduction in fish locomotion, similar to diazepam (DZP), which may involve the GABA

Iron nanoparticles (FeNP) present excellent magnetic properties and chemical stability, and for this reason, they are often configured into materials for a variety of potential uses in medical, biotechnological, and other applications. In this work, iron oxide nanoparticles functionalized with galactomannan (FeNP/Gal) from Caesalpinia pulcherrima were synthesized and submitted to characterization and evaluation of the cytotoxic activity. The functionalized nanoparticles were synthesized by co-precipitation and subjected to a process of surface modification with galactomannan and epichlorohydrin. These nanomaterials were characterized using infrared spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential thermogravimetric analysis (DTA), and scanning electron microscopy (SEM). 1D and 2D nuclear magnetic resonance (NMR) spectroscopy were also used in the structural analysis of the galactomannan. In addition, in vitro study was carried out to evaluate the cytotoxic activity of the FeNP/Gal nanoparticles on human cells of the HEK-293 strain (ATCC® CRL-1573). The FeNP/Gal nanoparticles had an average diameter of 13 ± 2 nm as opposed to 11 ± 2 nm for unreacted FeNP. The infrared spectrum of the FeNP/Gal nanoparticles presents characteristic absorbance bands of their chemical constituents, confirming that the iron oxide nanoparticles were functionalized with galactomannan. The cytotoxicity assay for the FeNP/Gal nanoparticles did not show significant cytotoxicity against HEK 293-Human embryonic kidney cell lines below 800 µg/mL However, this study points out the possibility of using hemicellulose and other plant-based polysaccharides to produce nanostructured materials for ​​tissue engineering and other biomedical applications.

Due to the increase in fungal resistance to existing drugs, a need exists to search for new antifungals. This study aimed to evaluate the antifungal activity of α, β, and δ-damascone and inclusion complexes with β-cyclodextrin against different Candida spp. The inclusion complex of β-damascone was prepared by the co-evaporation method using three molar proportions (1:1; 2:1; 3:1 (βDA-βCD)) and analyzed using Fourier transform infrared spectroscopy (FTIR). Standard Candida albicans (CA INCQS 40,006), Candida krusei (CK INCQS 40,095), and Candida tropicalis (CT INCQS 40,042) strains were used to evaluate antifungal activity. The substances were tested individually or in association with fluconazole (FCZ). The IC

A large number of infections are caused by multi-resistant bacteria worldwide, adding up to a figure of around 700,000 deaths per year. Because of that many strategies are being developed in order to combat the resistance of microorganisms to drugs, in recent times, chalcones have been studied for this purpose. Chalcones are known as α, β-unsaturated ketones, characterized by having the presence of two aromatic rings that are joined by a three-carbon chain, they are a class of compounds considered an exceptional model due to chemical simplicity and a wide variety of biological activities, which include anticancer, anti-inflammatory, antioxidants, antimicrobials, anti-tuberculosis, anti-HIV, antimalarial, anti-allergic, antifungal, antibacterial, and antileishmanial. The objective of this work was evaluate the antibacterial and antibiotic modifying activity of chalcone (E)-1-(2-hydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)prop-2-en-1-one against the bacteria Staphylococcus aureus carrying a NorA and MepA efflux pump. The results showed that chalcone was able to synergistically modulate the action of Norfloxacin and Ethidium Bromide against the bacteria Staphylococcus aureus 1199B and K2068, respectively. The theoretical physicochemical and pharmacokinetic properties of chalcone showed that the chalcone did not present a severe risk of toxicity such as genetic mutation or cardiotoxicity, constituting a good pharmacological active ingredient.

Introduction. Combretum leprosum (Combretaceae) is commonly found in the Northeast Region of Brazil and is known for several bioactivities, including antimicrobial ones. Because of increasing bacterial antibiotic resistance, natural products from several plants have been studied as putative adjuvants to antibiotic activity, including products from C. leprosum. Aims. This study was carried out to investigate the structural properties, bactericidal activity and antibiotic modifying action of the lupane triterpene 3β,6β,16β-trihydroxylup-20(29)-ene (CLF1) isolated from C. leprosum Mart. leaves. Methods. The CLF1 was evaluated by the Fourier transform infrared spectroscopy method and the antibacterial activity of this compound was assayed alone and in association with antibiotics by microdilution assay. Results. Spectroscopic studies confirmed the molecular structure of the CLF1 and permitted assignment of the main infrared bands of this natural product. Microbiological assays showed that this lupane triterpene possesses antibacterial action with clinical relevance against Staphylococcus aureus . The CLF1 triterpene increased antimicrobial activity against the multidrug-resistant Escherichia coli 06 strain when associated with the antibiotics gentamicin and amikacin. Synergistic effects were observed against the S. aureus 10 strain in the presence of the CLF1 triterpene with the antibiotic gentamicin. Conclusion. In conclusion, the CLF1 compound may be useful in the development of antibacterial drugs against the aforementioned bacteria.

Chalcones containing amino or acetamide groups on ring A and electron donating/withdrawing groups on ring B have been shown to have great cytotoxic potential against human cancer cell lines. In this work, a series of twenty chalcones, including nine 1-(4′-aminophenyl)-3-(substituted aryl)-2-propen-1-ones (1–9), nine 1-(4′-acetamidophenyl)-3-(substituted aryl)-2-propen-1-ones (1a–9a), and two 1-(3′-methoxy-4′-hydroxyphenyl)-3-(substituted aryl)-2-propen-1-ones (10, 11), were synthesized and submitted for initial biological screening using HCT-116 cells. Among the evaluated compounds, chalcone 6a showed strong and selective activity against HCT-116 cells (IC50 = 2.37 ± 0.73 µM). The preliminary structure–activity relationship analysis indicated that the cytotoxic effect of these compounds might be attributed to the combined effect of two electron withdrawing groups: the nitro group (NO2) at the meta-position of ring B and the acetyl group at the para-position of ring A. Moreover, chalcone 6a was able to induce G2/M cell cycle arrest and apoptosis at a concentration of 10 µM after 24 h of incubation. These data reinforce that compound 6a could be a promising lead compound for the future exploration of selective anti-colon carcinoma cancer agents.

The aim of this study was to evaluate the caffeic acid antioxidant and cytoprotective activity against Mercury Chloride (HgCl2) action. DPPH and iron chelation assays were performed to evaluate the antioxidant activity. The interaction between the metal and phenolic compounds was identified by Fourier-transform infrared spectroscopy (FTIR) and microbiological tests were performed using microdilution, obtaining the Minimum Inhibitory Concentration (MIC), the Minimum Bactericidal Concentration (MBC) and the Minimum Fungicidal Concentration (MFC). To evaluate cytoprotection in the plant model, a sub-allelopathic product concentration (32 μg/mL) and different heavy metal concentrations were used. Caffeic acid was observed to confer cytoprotection to Lactuca sativa seeds, allowing greater growth and development of both plant radicles and caulicles. This result may be attributed to the chelating and antioxidant effect of the caffeic acid, thereby reducing the toxicity of the metal. These results demonstrate the possibility of using natural products as an alternative for heavy metal chelation and to enable a greater development of plants present in contaminated areas. These results become important given the high environmental contamination by heavy metals recently, preventing the growth of important plants both from an environmental and economic point of view, thus providing a viable alternative for minimizing the problem becomes indispensable.

Staphylococcus aureus represents the most common etiologic agent of purulent infections, affecting humans and animals. Escherichia coli is one of the principal causes of infectious diseases, mainly diarrheal diseases due to enterotoxin action. There are many reports indicating that these bacteria are multidrug-resistant (MDR) pathogens.In this study, we investigated the antimicrobial and modulatory activities of 5-hydroxy-3,7,4'-trimethoxyflavone (VG.EF.CLII) against E. coli and S. aureus strains.5-Hydroxy-3,7,4'-trimethoxyflavone was isolated from Vitex gardneriana Schauer leaves and structurally characterized using nuclear magnetic resonance. The antibacterial effect of VG.EF.CLII and modulation of antibiotic activity, both determined by minimum inhibitory concentration, were assessed using microtiter plates.VG.EF.CLII showed bacterial growth inhibition at concentrations ≤512 μg/mL, and synergistic effects were observed for the modulation of two distinct antibiotic classes (the fluoroquinolone norfloxacin and the aminoglycoside gentamicin).5-Hydroxy-3,7,4'-trimethoxyflavone isolated from V. gardneriana showed promising antimicrobial activity against MDR bacterial strains S. aureus 358 and E. coli 27 when associated with the antibiotics norfloxacin and gentamicin. Therefore, this natural product can contribute to the control of bacterial resistance.

With the increase in bacterial resistance to antibiotics, many studies have been directed towards finding new agents with antibacterial activity, such as studies with natural products. These products can have antibacterial activity such as d -limonene as described in the literature. The aim of this study was to evaluate the antibacterial activity of d -limonene, isolated and complexed with β-cyclodextrin, and to evaluate its potentiating activity of different antibiotic classes. Antibacterial activity was determined by the broth microdilution method, obtaining in this way the Minimal Inhibitory Concentration (MIC), with the antibiotic modulatory activity being obtained using a sub-inhibitory concentration (MIC/8). d -Limonene showed a MIC equal to 256 μg/mL against standard S. aureus and 512 μg/mL against resistant P. aeruginosa. In the gentamicin modulatory activity, the isolated d -limonene presented synergism against S. aureus and E. coli bacteria. Thus, d -limonene showed relevant clinical antibacterial activity, for both Gram-positive and Gram-negative bacteria as well as a synergistic effect when associated with gentamicin. These results are promising in the combat against bacterial resistance, however further studies are needed to better elucidate the mechanisms of action.

Chagas disease is a disease that is emerging in North America and Europe countries. Benznidazole is the main drug available, but it has high toxicity and low efficacy in the chronic phase. In this way, researching new antichagasic agents is necessary. Thus, the aim of this study is to evaluate the effect of novel chalcones and the influence of chlorine substitutions on Trypanosoma cruzi and host cells. Unsubstituted (1), 4-chlorine substituted (2) and 2,4-chlorine substituted (3) chalcones were synthesized by Claisen-Schmidt condensation, characterized, and electrical distribution was assessed by Density Fuctional Theory (DFT). The host cells toxicity (LLC-MK2) was performed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) reduction assay. The effect on epimastigote (24, 48 and 72h), trypomastigote (24h) and amastigotes (24 h) was evaluated. Flow cytometry assays were performed with 7-Aminoactinomycin D (7-AAD) and Annexin-PE, Dichlorofluorescein diaceteate (DCFH-DA) and Rhodamine123 (Rho123). Finally, molecular docking predicted interactions between chalcones and cruzain (TcCr) and trypanothione reductase (TcTR). The toxicity on host cells was reduced almost twenty times on chlorine substituted molecules. On epimastigote and trypomastigote forms, all substances presented similar effects. After treatment with molecule 3, it was observed a decrease in infected cells and intracellular amastigotes. Their effect is related to necrotic events, increase of cytoplasmic Reactive Oxygen Species (ROS) and mitochondrial dysfunction. Also, this effect might be associated with involvement of TcCr and TcTR enzymes. Therefore, the results showed that chlorine substitution on chalcones reduces the host cell's toxicity without compromising the effect on Trypanosoma cruzi Y strain forms, and it occurs over membrane damage, oxidative stress and possible interactions with TcCr and TcTR.

Benzodiazepines are highly effective in combating anxiety; however, they have considerable adverse effects, so it is important to discover new safe anxiolytic agents. This study was designed to investigate the anxiolytic and anticonvulsant effect of natural product 2-hydroxy-3,4,6-trimethoxyacetophenone (HTMCX) and its possible mechanisms of action in adult zebrafish. The open field and light / dark tests (n = 6 animals/group) were used to assess anxiety and pentylenetetrazole (PTZ) as a seizure inducer. The 96-hour acute toxicity of HTMCX was also investigated. HTMCX (1, 3, and 10 mg / kg; v.o.) was not toxic and affected locomotor activity. The highest doses (3 and 10 mg / kg; v.o.) produced signs of anxiolytic action in the light / dark test, and this effect was abolished by the pizotifen (antagonist 5HTR1 and 5HTR2A / 2C), having the potential to form a complex in the same region of the site indicating that the anxiolytic effect via the serotonergic mechanism. However, the anxiolytic effect of HTMCX has not been abolished by flumazenil (antagonist GABARA), cyproheptadine (antagonist 5HTR2A), and granisetron (antagonist 5HTR3A / 3B). Therefore, HTMCX demonstrated an anxiolytic effect, suggesting that the 5HTR1 and 5HTR / 2C receptors may be involved in the pharmacological performance of this acetophenone in the central nervous system.

With the spread of bacterial resistance against clinically used antibiotics, natural plant-derived products are being studied as new sources of antibacterial molecules. Manilkara zapota is a common plant species in the American continent that is used as a food source. Studies show the M. zapota extract is rich in phenolic substances that can serve as basic molecules for the pharmaceutical industry. An extract from fresh M. zapota leaves was produced and tested to identify the compounds present, as well as its direct antibacterial and clinical antibiotic modulatory activities. To analyze the results, a new statistical methodology based on the Shannon-Wiener index was tested, capable of correcting distortions in heterogeneous environments. The Hydroethanolic Extract of Manilkara zapota leaves (HEMzL) presented a wide variety of phenolic products, as well as tannins, in the UPLC analysis. The extract showed direct antibacterial activity against the standard Staphylococcus aureus strain, however, it either acted antagonistically when associated with the tested antibiotics, or it did not present statistical significance when compared to the control. This demonstrates a need to be cautious when associating natural products with antibiotics for clinical use, as a hindrance to infectious treatments may occur. As for the statistical analysis mechanism tested, this proved to be effective, reducing false negatives at low antibiotic concentrations and false positives at high concentrations in the microdilution plate.

Staphylococcus aureus is responsible for a series of infections occurring in both human and animal hosts. S. aureus SA1199B is a strain resistant to hydrophilic fluoroquinolone due to overproduction of the NorA efflux pump that has been used as a microbial model to evaluate if a compound act as efflux pump inhibitor. Finding substances from natural or synthetic origin able to reverse resistance mechanisms like those of efflux pumps is a challenge. The use of Chalcones and their derivatives is of great chemical and pharmacological interest, as they present a simple structure and several pharmacological activities. This study aims to evaluate the antibacterial potential of 4 synthetic chalcones, as well as to evaluate their action in the modulation of Norfloxacin resistance against the strain SA1199B strain. Microdilution assays were performed for evaluation of the antimicrobial activity. For evaluation of the modulating effect on resistance to Norfloxacin or EtBr, MIC values of these compounds were determined in the absence or presence of subinhibitory concentrations used of each chalcone. MICs values of both Norfloxacin and EtBr were significantly reduced in the presence of all tested chalcones, indicating that inhibition of the active efflux of these compounds by NorA could be a possible mechanism of action of the chalcones. These results show that the compounds studied have a high potential as a NorA inhibitor, with the best modulating effect verified for the compound 3. Pharmacokinetic and toxicity predictive studies indicated a high intestinal absorption and good volume of distribution for chalcones by oral administration, activity in the central nervous system and ease to be transported between biological membranes. Emphasizing that analogs 1 and 4 were easily metabolized by CYP3A4 enzyme, constituting a pharmacological active ingredient without toxic risk due to metabolic activation. These chalcones combined with Norfloxacin could be a promise technological strategy to be applied in the treatment of infections caused by S. aureus overproducing NorA.

Croton blanchetianus is known as ‘marmeleiro preto’, a very widespread shrub in Northeast Brazil. Terpenoids, steroids and phenolic compounds are among the reported secondary metabolites of the Croton genus that are a potential source of bioactive compounds. This study evaluated the anxiolytic potential of clerodine-type diterpene, sonderianin (CBWS) isolated from the stem bark of C. blanchetianus and its mechanism of action in adult zebrafish (Danio rerio) (ZFa). The anticonvulsant and anti-acetylcholinesterase effects have also been explored. ZFa (n = 6/group) were treated intraperitoneally (ip; 20 µL) with CBWS (4, 12 and 40 mg/kg) and vehicle (3% DMSO; 20 µL) and subjected to locomotor activity tests, as well as toxicity acute 96 h. CBWS was also administered for analysis in the light/dark test. The involvement of the serotonergic system (5-HT) was investigated using 5-HTR1, 5-HTR2A/2C and 5-HTR3A/3B receptor antagonists. Anxiolytic doses were tested for pentylenetetrazol-induced seizure in ZFa. The inhibitory activity of the enzyme acetylcholinesterase (AChE) was measured. CBWS was not considered toxic and reduced locomotor activity. The results of the present study identified for the first time the interaction of the diterpene sonderianina in the CNS. This study provides evidence that CBWS has an anxiolytic effect mediated by serotonergic (5-HT) involvement and anti-acetylcholinesterase action. The 5-HTR1 and 5-HTR2A/2C receptors may be implicated in the low anticonvulsant effect in CBWS. Communicated by Ramaswamy H. Sarma

Benzodiazepines (GABA receptor agonists) and serotonin reuptake inhibitors (SSRIs) are the drugs of choice for the treatment of anxiety. However, they have considerable adverse effects, so it is important to discover new anxiolytic agents. In this work, the 4′-[(1E,2E)-1-(2-(2′,4′-dinitrophenyl)hydrazone-3-(4-methoxyphenyl)allyl)aniline (HYDRAZDN) was synthesized and characterized by 1H and 13C NMR, 2D-NMR, ATR-FTIR, FT-Raman, and UV-Vis spectroscopy, and their structural and spectroscopic proprieties were evaluated by quantum chemistry theoretical calculations. Properties such as drug-likeness and pharmacokinetics were also estimated. The anxiolytic-like effect of the compound was also evaluated using adult zebrafish (Danio rerio). The results showed that the HYDRAZDN compound caused a reduction in zebrafish locomotor activity and induced maximum permanence of zebrafish in the clear zone at a dose of 40 mg/kg, an effect similar to the effect of positive control diazepam (DZP: 40 mg/kg). To identify the mechanism of action of the anxiolytic effect of this compound, we used flumazenil, an antagonist at the benzodiazepine binding site at GABAA receptors. The treatment with the highest dose of HYDRAZDN (40 mg/kg) and DZP (40 mg/kg) caused anxiolytic behavior in the animals that spent most of their time in the dark region of the aquarium. This effect was reduced by flumazenil, indicating that anxiolytic activity of the synthesized hydrazone occurs through the GABAergic system.

Croton zehntneri is a plant known as canelinha de cunha, prevalent in the northeast region of Brazil. Many constituents of the vegetable have already been studied, and their pharmacological properties have been proven, but this is the first study to analyze the antinociceptive effect in adult zebrafish (ZFa) of the triterpene acetyl aleuritolic acid (AAA) isolated from the stem bark. The animals (ZFa; n = 6/group) were treated intraperitoneally (ip; 20 μL) with AAA (0.1 or 0.3 or 1.0 mg/mL) or vehicle (0.9% saline; 20 μL), and submitted to the locomotor activity test, as well as 96 h acute toxicity. Other groups (n = 6/each) received the same treatments and underwent acute nociception tests (formalin, cinnamaldehyde, glutamate, acid saline, capsaicin, and hypertonic saline). Possible neuromodulation mechanisms were evaluated. AAA (0.1 or 0.3 or 1.0 mg/mL) reduced the nociceptive behavior induced by acid saline and capsaicin, as well as inhibited corneal nociception induced by hypertonic saline, both without altering the animals’ locomotor system and without toxicity. These analgesic effects of AAA were significantly (p > 0.05) similar to those of morphine, used as a positive control. The antinociceptive effect of AAA was inhibited by methylene blue, ketamine, camphor, ruthenium red, amiloride, and mefenamic acid. The antinociceptive effect of AAA on the cornea of animals was inhibited by capsazepine. Therefore, AAA showed pharmacological potential for the treatment of acute pain, and this effect is modulated by cGMP, NMDA receptors, transient receptor potential channels (TRPs), ASICs and has pharmacological potential for the treatment of corneal pain modulated by the TRPV1 channel.

A large number of infections are caused by Gram-positive and Gram-negative multi-resistant bacteria worldwide, adding up to a figure of around 700,000 deaths per year. The indiscriminate uses of antibiotics, as well as their misuse, resulted in the selection of bacteria resistant to known antibiotics, for which it has little or no treatment. In this way, the strategies to combat the resistance of microorganisms are extremely important and, essential oils of Croton species have been extensively studied for this purpose. The aim of this study was to carry the evaluation of antibacterial, antibiofilm, antioxidant activities, and spectroscopic investigation of essential oil from Croton piauhiensis (EOCp). The EOCp exhibited antimicrobial activity against Gram-positive and Gram-negative bacteria with required MICs ranging from 0.15 to 5% (v/v). In addition, the MBC of the EOCp for Staphylococcus aureus ATCC 25923 and ATCC 700698, were 0.15 and 1.25%, respectively. Moreover, the EOCp significantly reduced significantly the biofilm production and the number of viable cells from the biofilm of all bacterial strains tested. The antioxidant potential of the EOCp showed EC