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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

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.

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.

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...

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.

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.

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.

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.

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

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.

Chalcones and their derivatives are substances of great interest for medicinal chemistry due to their antibacterial activities. As the bacterial resistance to clinically available antibiotics has become a worldwide public health problem, it is essential to search for compounds capable of reverting the bacterial resistance. As a possibility, the chalcone class could be an interesting answer to this problem. The chalcones (2E)-1-(4'-aminophenyl)-3-(phenyl)‑prop-2-en-1-one (APCHAL), and (2E)-1-(4'-aminophenyl)-3-(4-chlorophenyl)‑prop-2-en-1-one (ACLOPHENYL) were synthesized by the Claisen-Schmidt condensation and characterized by 1H and 13C nuclear magnetic resonance (NMR), Fourier-transform infrared (FT-IR), and mass spectrometry (MS), In addition, microbiological tests were performed to investigate the antibacterial activity, modulatory potential, and efflux pump inhibition against Staphylococcus aureus (S. aureus) multi-resistant strains. Regarding the S. aureus Gram-positive model, the APCHAL presented synergism with gentamicin and antagonism with penicillin. APCHAL reduced the Minimum inhibitory concentration (MIC) of gentamicin by almost 70%. When comparing the effects of the antibiotic modifying activity of ACLOPHENYL and APCHAL, a loss of synergism is noted with gentamicin due to the addition of a chlorine to the substance structure. For Escherichia coli (E. coli) a total lack of effect, synergistic or antagonistic, was observed between ACLOPHENYL and the antibiotics. In the evaluation of inhibition of the efflux pump, both chalcones presented a synergistic effect with norfloxacin and ciprofloxacin against S. aureus, although the effect is much less pronounced with ACLOPHENYL. The effect of APCHAL is particularly notable against the K2068 (MepA overexpresser) strain, with synergistic effects with both ciprofloxacin and ethidium bromide. The docking results also show that both compounds bind to roughly the same region of the binding site of 1199B (NorA overexpresser), and that this region overlaps with the preferred binding region of norfloxacin. The APCHAL chalcone may contribute to the prevention or treatment of infectious diseases caused by multidrug-resistant S. aureus.

Background: Chalcones are part of a family of small phenolic compounds that are being extensively studied for presenting a diversity of molecular structures and biological activities. In this paper, two chalcones, (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(3-nitrophenyl)prop-2-en-1-one (1), (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(4-nitrophenyl)prop-2-en-1-one (2), were synthesized by Claisen&ndash, Schmidt condensation. Methods: The molecular structures of these chalcones were determined by Nuclear Magnetic Resonance and characterized by infrared, Raman spectroscopy, and electrochemical analysis at room temperature. Vibrational wavenumbers were predicted using Functional Density Theory (DFT) calculations, and their normal modes were analyzed in terms of potential energy distribution (PED). Besides this, DFT calculations were performed to obtain the molecular orbitals and their quantum descriptors. The UV-Vis absorption spectrum of the synthesized chalcones was measured and compared with each other. In addition, analyses of antimicrobial activity and modulation of antibiotic resistance were carried out to assess the antibacterial potential of these chalcones. Results: The vibrational spectra of polycrystalline chalcones obtained by ATR-FTIR , FT-Raman and DFT calculations allowed a complete assignment of the vibrational modes, and revealed the quantum chemical parameters. Both chalcones did not show good responses when associated with the antibiotics Ciprofloxacin and Cephalexin against S. aureus 10 and E. coli 06 strains. However, a significant potentiating of the Gentamicin activity against S. aureus 10 and E. col 06 strains was observed for chalcone 2. On the other hand, when associated with Norfloxacin, an antagonistic effect was observed. The results found for EtBr suggest that, although the tested chalcones behave as efflux pump inhibitors, probably inhibiting other efflux pumps, they were not able to inhibit NorA. Thus, these synthetic chalcones are not recommended for use in association with Norfloxacin against strains of S. aureus 1199-B that overexpress the NorA gene. Conclusions: Spectroscopic data confirmed the structure of the chalcones, and chalcone 2 showed potential as an adjuvant in antibiotic therapy.

Antibiotic for clinical use lose its effectiveness over time due to bacterial resistance. In this work, four chalcones with modifications in their ligands were synthesized from the natural product 2-hydroxy-3,4,6-trimethoxyacetophenone, characterized by nuclear magnetic resonance (NMR) and infrared spectroscopy, and tested in bacterial models to investigate the direct and modifiers effects of the antibiotic activity of these four novel chalcones. The tests followed the broth microdilution methodology to obtain the Minimum Inhibitory Concentration (MIC). The MIC/8 of the products were used in the resistance reversion test. The chalcone 2 showed the best result in terms of direct activity, with MIC 645 μg/mL for Staphylococcus aureus and 812 μg/mL for Escherichia coli. While, for the bacterial resistance reversal test, the chalcones presented several synergistic interactions, being that chalcone 4 had the best interaction with the tested antibiotics. It was found that the type of ligand, as well as its position in the ring, interferes in the modulation of the antibiotic activity. Our results show that chalcones are strong candidates to be used as antibacterial drug or in combination with antibiotics for the treatment of infections caused by multidrug-resistant (MDR) strains.

Chalcones are α,β-unsaturated ketones containing the 1,3-diarylprop-2-en-1-one framework. This study aims to evaluate the potentiation of antibacterial activity by the chalcone (E)-1-(4-aminophenyl)-3-(furan-2-yl)-prop-2-en-1-one (C13H11NO2), hereafter named AFPO, against multi-resistant strains of Staphylococcus aureus and Escherichia coli. AFPO was synthesized using the Claisen-Schmidt condensation reaction, and the molecular structure was confirmed by nuclear magnetic resonance (NMR). The antibacterial and potentiating properties of AFPO were evaluated by measuring the minimum inhibitory concentration (MIC) using microdilution plates. The AFPO MIC was 1024 μg/mL for the S. aureus 10 strain, revealing synergy in combination with the following antibiotics: penicillin, norfloxacin, ampicillin/sulbactam, and gentamicin. The AFPO MIC was 256 μg/mL for the E. coli 06 strain, and synergy was observed with norfloxacin, gentamicin, and penicillin. The potentiation of antibacterial activity by AFPO was observed against the strains of S. aureus 10 and E. coli 06.

Objective Efflux pumps are transmembrane proteins associated with bacterial resistance mechanisms. Bacteria use these proteins to actively transport antibiotics to the extracellular medium, preventing the pharmacological action of these drugs. This study aimed to evaluate in vitro the antibacterial activity of 1,8-naphthyridines sulfonamides, as well as their ability to inhibit efflux systems of Staphylococcus aureus strains expressing different levels of the NorA efflux pump. Methods The broth microdilution test was performed to assess antibacterial activity. Efflux pump inhibition was evaluated in silico by molecular docking and in vitro by fluorometric tests, and the minimum inhibitory concentration (MIC) was determined. The MIC was determined in the association between 1,8-naphthyridine and norfloxacin or ethidium bromide. Results The 1,8-naphthyridines did not show direct antibacterial activity. However, they effectively reduced the MIC of multidrug-resistant bacteria by associating with norfloxacin and ethidium bromide, in addition to increasing the fluorescence emission. In silico analysis addressing the binding between NorA and 1,8-naphthyridines suggests that hydrogen bonds and hydrophilic interactions represent the interactions with the most favourable binding energy, corroborating the experimental data. Conclusion Our data suggest that 1,8-naphthyridines sulfonamides inhibit bacterial resistance through molecular mechanisms associated with inhibition of the NorA efflux pump in S. aureus strains.

Chalcones and their derivatives exhibit a broad spectrum of pharmacological activities, including antiproliferative activities. Accordingly, they are deemed robust anticancer candidates for cytotoxicity assays. Herein, we synthesized and characterized four chalcones using nuclear magnetic resonance (1H NMR and 13C NMR), Fourier transform Raman (FT-Raman), attenuated total reflection Fourier transform infrared (ATR-FTIR), and ultraviolet-visible (UV–vis) spectroscopy. Theoretical calculations of quantum chemistry were performed to obtain data regarding normal vibration modes, frontier molecular orbitals, molecular electrostatic potential maps, theoretical UV–vis spectra, and quantum chemical parameters expected for these chalcones. In addition, we evaluated the cytotoxic potential of these compounds. For synthesized compounds, quantum chemical calculations demonstrated excellent correlation with experimental data. The electronic properties revealed that chalcones 1 and 4 possess a higher electrophilic character, while chalcones 2 and 3 possess a higher nucleophilic character. Chalcone 3 demonstrated the highest value of HOMO energy, indicating the greatest propensity to donate electronic density among the four compounds. According to the HOMO-LUMO energy gap and global hardness, the reactivity of chalcones should follow the order 1

Bacterial resistance induced by efflux pumps is a frequent concern in clinical treatments involving multi-resistant bacteria. Staphylococcus aureus is a microorganism responsible for several types of infections and has several strains carrying efflux pumps, among them are the strain 1199B (NorA overexpresser), and the strain K2068 (MepA overexpresser). In this work, four chalcones derived from Croton anisodontus with modifications in the B ring in their structures were tested regarding their ability to inhibit NorA and MepA efflux pumps. The efflux pump inhibition mechanism was tested with the ethidium bromide substrate in the presence and absence of standard efflux pump inhibitors. The minimum inhibitory concentration values were also compared to those of strains that do not overexpress these efflux pumps. In order to gain some insights about the efflux pump mechanisms of these chalcones, two homology models were created (NorA and MepA) for a docking procedure. In addition, the ADME properties (absorption, distribution, metabolism and excretion) were also evaluated. The tested chalcones promoted synergism of the norfloxacin antibiotic by inhibiting associated efflux pumps. All four tested chalcones appear to bind to the binding sites of the efflux pump models in the same fashion as other chalcones with efflux pump inhibition capabilities. It was also verified that the chalcones 1–4 are well absorbed in the intestine, but with a decrease in their bioavailability, resulting in a low volume of distribution in the blood plasma, in addition to having a mild CNS activity. However, the chalcone 3 and 4 were not toxic due to metabolic activation. Whereas the chalcones 1 and 2 present a mutagenic risk, depending on the oral dose administered. The tested chalcones have not antibacterial activity; however, they are capable of inhibiting efflux pumps for the 1199B and K2068 strains. They promoted synergism of the norfloxacin antibiotic by inhibiting associated efflux pumps, as well as other associated mechanisms.

In this work, an ibuprofen derivative 2-(4-isobutylphenyl) -N'-phenylpropanohydrazide (ACPHZN) was synthesized and characterized by NMR, ATR-FTIR, FT-Raman, and UV-Vis spectroscopy, while their structural and spectroscopic properties were investigated using DFT calculations. In vivo study using animal model in an adult Zebrafish (Danio rerio), and molecular docking was performed. In addition, molecular descriptors of the properties of absorption, distribution, metabolism and excretion, and toxicity (ADMET) were obtained. The data calculated for ibuprofen derivative are in accordance with the experimental values. From the assays in adult zebrafish, it was found that the ibuprofen derivative was non-toxic and exhibited analgesic properties through the TRPA1, TRPV1 and TRPM8 channels. Molecular docking revealed six interactions of ACPHZN with residues of the capsaicin binding site, and a more favorable affinity energy (-9.0 kcal / mol). ADMET studies suggest that ACPHZN has a pharmacological principle as an oral drug based on a longer half-life in the human body.

Six 2’-hydroxychalcones were synthesized and characterized by NMR, FT-Raman, ATR-FTIR, and UV-Vis. These chalcones alone and in combination with the ciprofloxacin, penicillin, and erythromycin antibiotics were tested against multiresistant strains of Staphylococcus aureus. It was also verified by in vitro and in silico studeis the capacity of these chalcones to inhibit the NorA efflux pump. The MICs values of ciprofloxacin were reduced in the presence of all tested chalcones. For norfloxacin antibiotic, the chalcones A1, A4, A5 and A6 promoted the reduced in the MIC values. The A2 chalcone was the only one to reduce the MIC values when associated with penicillin. Any chalcones were not able to reduce MIC values when associated with erythromycin. These results indicate that the synergistic effects demonstrated for the synthesized chalcones were influenced by the introduction of a furanic ring (A1), a chlorine atom and a methoxy group at the C4 position (A2 and A4), a second double bond (A5), and a fluorine atom at the C2 position (A6). The ADMET analysis predicts that the chalcones A2, A3, A5 and A6 have easier cell permeation. The nucleophilic region makes the A5 chalcone capable of covalently bonding with plasma proteins, and the presence of oxygenated aromatic substitutions makes the chalcones A1 and A4 more water-soluble and consequently easier to excrete. On the other hand, the substitution of the methoxy group of the A4 chalcone makes it more susceptible to O-demethylation reactions by the CYP3A4 isoenzyme. The molecular docking revealed that all six chalcones could hinder the binding of norfloxacin to the NorA efflux pump.

In this study, a spray drying technique was used to encapsulate bixin in the galactomannan polymer to give greater stability to this carotenoid. The microparticles were characterized using physical-chemical techniques, quantum chemical calculations, and evaluated the particle sizes, encapsulation efficiency, stability, controlled release, and toxicological potential. The bixin was successfully encapsulated, with an average size of 5.55 ± 0.50 µm, and infrared spectroscopy showed no chemical reaction between bixin and galactomannan during the encapsulation process. The values for the encapsulation efficiency were higher than 90 %, indicating that galactomannan was a good encapsulating agent. A stability test revealed that microencapsulation provides significant protection for bixin. It was observed that the microparticles were capable of releasing the pigment homogeneously and gradually. The absence of toxicity of these materials allows for their use within the food industry, since there is a need for new products that combine low toxicity, efficiency, and low cost.

This study aimed to evaluate the antibacterial activity and to verify, in silico and in vitro, the inhibition of efflux mechanisms using a series of synthesized 1,8-naphthyridines sulfonamides against Staphylococcus aureus strains carrying MepA efflux pumps. The chemical synthesis occurred through the thermolysis of the Meldrum's acid adduct. The sulfonamide derivatives were obtained by the sulfonylation of 2-amino-5‑chloro-1,8-naphthyridine with commercial benzenesulfonyl chloride. Antibacterial activity was assessed by the broth microdilution test. Efflux pump inhibitory capacity was evaluated in silico by molecular docking and in vitro by analyzing synergistic effects on ciprofloxacin and ethidium bromide (EtBr) and by EtBr fluorescence emission assays. The following 1,8-naphthyridines were synthesized: 4-methyl-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10a); 2,5-dichloro-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10b); 4-fluoro-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10c); 2,3,4-trifluoro-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10d); 3-trifluoromethyl-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10e); 4‑bromo-2,5-difluoro-N-(5‑chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10f). The 1,8-naphthyridines derivatives associated with sulfonamides did not show antibacterial activity. However, they showed a favorable pharmacokinetic profile with possible MepA efflux pump inhibitory action, demonstrated in molecular docking. In addition to the promising results in reducing the concentration of intracellular EtBr. 1,8-naphthyridines act as putative agents in the inhibitory action of the MepA efflux pump.

There has been a rapid increase in the incidence and prevalence of opportunistic bacterial infections. Inappropriate use of current antibiotics has continuously contributed to the emergence of resistance to conventional antibiotic therapy. Therefore, the search for natural molecules that are able to combat infections is of great public interest, and many of these compounds with antimicrobial properties can be obtained from phytochemical studies of medicinal plants. In this context, this study reports the isolation and characterization of the flavonoid, kaempferol 7-O-β-D-(6″-O-cumaroyl)-glucopyranoside, from Croton piauhiensis leaves. Additionally, the intrinsic antimicrobial action of the compound and its enhancement against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains were assessed. The minimum inhibitory concentration (MIC) of the compound was determined using broth microdilution assays. To evaluate the modulatory effect of the flavonoid, the MIC of antibiotics amikacin and gentamicin, belonging to the class aminoglycosides was assessed, with and without the compound in sterile microplates. The results of intrinsic antibacterial activity tests revealed that the compound had no antibacterial activity against strains tested at concentrations1024 μg/mL. The combination of the flavonoid at a concentration of 128 μg/mL with gentamicin presented synergistic effects against S. aureus 10 and E. coli 06, and also reduced the MIC from 16 μg/mL to 4 μg/mL and 8 μg/mL, respectively. Amikacin also showed synergistic effects against S. aureus 10 and E. coli 06. We also observed reduced MIC for both, from 128 μg/mL to 32 μg/mL; however, antagonism for P. aeruginosa increased the MIC from 16 μg/mL to 64 μg/mL. The combination of the flavonoid with the aminoglycosides may be an alternative to potentiate the expected results in treatment against S. aureus and E. coli, since their association leads to a synergistic effect, reducing the MIC of these drugs and decreasing the dose necessary for therapeutic success.

Chalcones are open-chain flavonoids characterized by two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system. Over the last several years, chalcones have instigated the interest of chemical and pharmacological researchers due to their simple chemical structure and varied biological activities. Here, we performed the electronic properties, of the chalcone, (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(4-methoxyphenyl) prop-2-en-1-one synthesized by Claisen-Schmidt condensation reaction. The density functional theory method was used with the B3LYP/6-311++G(d,p) level of theory to compute the structural, electronic, and reactivity properties of the chalcone. In addition, microbiological tests were performed to investigate the modulator potential and efflux pump inhibition on Staphylococcus aureus multi-resistant strains. The spectroscopic data analyses allowed drawing the molecular structure of the chalcone synthetized with subsequent confirmation using the quantum chemical calculations. The addition of chalcone to the growth medium caused a synergic effect by reduction of the minimum inhibitory concentration (MIC) values for ciprofloxacin strain. Docking results showed that the chalcone docks in almost the same way as the antibiotic against a MepA model. Druglikeness criteria based on the rules of Lipinski and Veber evaluated that the chalcone has the ideal physicochemical and pharmacokinetic properties to be a good candidate for drug orally. The results confirm the structure of the synthesized chalcone and revealing that the compound can be used as a possible inhibitor of the Mep A efflux pump.

Zebrafish is a model animal that is used for neurobehavioral studies. It is an excellent model organism for pharmacological studies and/or safety research at an early stage of drug development. In this work, the chalcone (2E, 4E)-1-(2‑hydroxy-3,4,6-trimethoxyphenyl)-5-phenylpenta-2,4‑dien‑1-one, was synthesized by the Claisen-Schmidt condensation from two natural products: 2‑hydroxy-3,4,6-trimethoxyacetophenone and cinnamaldehyde. The molecular structure of this compound was confirmed by spectroscopic methods such as NMR, Infrared, UV–vis, and quantum chemical calculations. In addition, the anxiolytic-like effect of the cinnamaldehyde chalcone in adult zebrafish (Danio rerio) was evaluated. The results showed that chalcone caused an approximately 80% reduction in zebrafish locomotor activity and induced maximum permanence of zebrafish in the clear zone (61.16%) at a dose of 0.5 mg kgl−1. The data suggest that the cinnamaldehyde chalcone has anxiolytic activity.

Naphthyridines represent a class of heterocyclic compounds formed by two condensed aromatic rings. This study aimed to evaluate the antibacterial activity and in vitro inhibition of efflux resistance mechanisms of a series of 1,8-naphthyridine sulfonamides against strains carrying Tet(K) and MsrA efflux pumps. The efflux pump inhibitory capacity was evaluated by analyzing synergistic effects between 1,8-naphthyridine sulfonamides and standard antibiotics, as well as ethidium bromide. The following 1,8-naphthyridines were used: 4-methyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Naph 1); 2,5-Dichloro-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Naph 2); 2,3,4-trifluoro-N-(5-chloro-1,8-naphthyridin-2-yl)benzenesulfonamide (Naph 7); 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Naph 9). The 1,8-naphthyridine sulfonamide derivatives possessed a potential Tet(K) and MsrA efflux pump inhibitory action.

Curcumin, along with its derivatives, form a large class of natural and synthetic compounds with notable biological activity. However, their highly reactive β-diketone moiety renders this type of compounds unstable at pH above 6.5. The substitution of this group for a mono-carbonyl solves this problem, while improving antibacterial and anti-inflammatory activities. A thiophene curcuminoid, (1E,4E)-1,5-Di(thiophen-2-yl)penta-1,4-dien-3-one (DB Thiophene), has been synthesised and its molecular and spectroscopic characterization is reported, as well as a complete vibrational assignment. An efflux pump inhibition assay determined that DB Thiophene exhibits a remarkable NorA and MepA efflux pump inhibition activity. Molecular docking studies were carried out in order to understand this inhibition mechanism.

The acetophenone 2-hydroxy-3,4,6-trimethoxyacetophene (C11O5H14, hereafter named as HTMCX) was obtained from the stem bark of Croton anisodontus Mull.Arg., an endemic species found in the caatinga of Northeast Brazil. The HTMCX crystal was investigated via Raman spectroscopy as a function of the temperature and pressure, in the intervals ranging from 300 to 8 K and from ambient pressure up to 9.7 GPa, respectively. In low-temperature experiments, we observed changes in the slope of the wavenumber versus temperature curves in the spectral range of 30–350 cm−1 at ∼ 210 K, as well as discontinuities in the wavenumber of modes in the region for wavenumbers higher than 1300 cm−1. These modifications are compatible with a conformational change occurring at around 210 K. Regarding the high-pressure experiments, we found that the wavenumber for modes located in the low-wavenumber region (ω

In this work we present a study of the structural and vibrational properties of the chalcone (2E)-1-(4-aminophenyl)-3-(furan-2-yl)prop-2-en-1-one monohydrate, C13H11O2N·H2O, a strong candidate for fluorescent probes, luminescent materials and optoelectronic devices. The crystalline structure of this chalcone monohydrate was determined at 273 K using single-crystal X-ray diffraction. The Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) and Fourier Transform-Raman (FT-Raman) spectra of the crystal were recorded at room temperature in the regions 600–4000 cm−1 and 40–4000 cm−1, respectively. Vibrational wavenumbers were predicted using Density Functional Theory (DFT) calculations with B3LYP exchange-correlation functional with the B3LYP functional and 6-31G(d) basis set. A comparison with experimental spectra using a hydrated model allowed us to assign all of the normal modes of this crystal. Additionally, we report the UV–Vis spectra and the Hirshfeld surface analysis of the AFPO crystal.

The compound 4-(Phenylsulfonyl) morpholine belongs to the class of sulfonamides, which are widely used in the treatment of a large number of diseases caused by microorganisms. This compound has a morpholine group, which is also known for its antimicrobial properties. The aim of the present study was to investigate the antimicrobial and modulating activity of 4-(Phenylsulfonyl) morpholine against standard and multi-resistant strains of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and strains of the fungi Candida albicans, C. tropicalis and C. krusei. Antimicrobial activity was assessed based on the minimum inhibitory concentration (MIC) using the microdilution method. MIC was ⩾1024μg/mL for all microorganisms. Regarding modulating activity, the most representative effect occurred with the combination of 4-(Phenylsulfonyl) morpholine at a concentration of 128μg/mL (MIC 1/8) and amikacin against P. aeruginosa 03, with a reduction in MIC from 312.5 to 39.06μg/mL.