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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.

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.

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.

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.

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 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.

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.

Plants are natural sources of several bioactive substances, which have been found in extracts, secondary metabolites, and essential oils. Several biological activities have been attributed to essential oils as antiviral, insecticidal, antiparasitic, antioxidant, and antimicrobial. The indiscriminate use of antibiotics has increased the development of resistance mechanisms of microorganisms. Thus, search for efficient natural compounds with antimicrobial activity and low toxicity has increased, so essential oils have been a promising alternative for combating microbial infections. This study was carried out to investigate the seasonality effects on the infrared absorbance spectra, antibacterial activity, and antibiotic potentiating activity of essential oils from Vitex gardneriana leaves. Essential oils were extracted from V. gardneriana Schauer leaves the seasonal period from January to December 2016 and characterized by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. The antibacterial effect of these oils and antibiotic potentiating activity, both determined by the minimum inhibitory concentration, were assessed using microtiter plates. For the first time, we present the use of infrared absorbance spectra of these essential oils and show the influence of seasonality on them. Synergistic effects were observed for the essential oils associated with the antibiotics tested (gentamicin, ampicillin, and ofloxacin). The main influence of seasonality on the infrared absorbance spectra of the essential oils of the V. gardneriana occurred in the June month (last month of the rainy season). In regard to antibacterial activity test, the essential oils of the V. gardneriana leaves did not show a direct effect on the strains tested. However, the essential oils when associated with the antibiotics showed variations in the minimum inhibitory concentration with the months of the seasonal period, indicating synergistic effects against Escherichia coli and Staphylococcus aureus bacterial resistance.

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.

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.

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.