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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.

Paullinia cupana (Kunth), popularly known as guarana, is a plant species from the Amazon Region of Brazil that stands out for being one of the most promising herbal medicines of the Brazilian flora since it has relevant biological properties. However, studies are still needed to use this species as a direct approach to evaluate aspects related to behavior and oxidative stress in invertebrate model animals. In this context, we aimed to evaluate the stimulant and the antioxidant effects of P. cupana in lobster cockroach Nauphoeta cinerea. For that, cockroaches were exposed to a diet separately supplemented by the decoction of P. cupana powder decoction at increasing concentrations of 1, 25, 50 and 100 mg/g for 42 days. Behavioral and biochemical assays were performed, respectively, to assess the locomotor/exploratory performance and oxidative stress marker levels of the cockroaches. They exhibited an outstanding increase in the locomotion performance and in the cell viability content, as well as in the protein and non-protein thiol levels. Moreover, there was a decrease in lipid peroxidation levels and in free Fe2+ ion contents. Together, our results demonstrate the stimulant and the antioxidant capacity of P. cupana by acting positively in behavioral patterns and by regulating oxidative stress markers in lobster cockroach N cinerea. These findings encourage further laboratory analyzes in order to better enlighten the specific mechanisms of action attributed to guarana.

Background: Saline stress is an important environmental factor that limits the productivity of numerous agricultural crops, such as onion (Allium cepa L.), a vegetable present in gardens and used in various ways. Pulegone has been identified as a component that has a large number of biological functions. Objective: The aim of this study was to investigate the effect of pulegone (100 and 500 μg/mL) on the morphological and biochemical changes to onions induced by stressing seeds with NaCl. Method: Soil composition, emergence percentage and its inhibition, emergence speed index (ESI), leaf and root parameters, malondialdehyde (MDA) content, free iron content and chelation/oxidation capacity (Fe2+) were measured following 120 days of treatment. Results: Pulegone was able to significantly improve the changes in ESI caused by saline stress, not restoring other emergence parameters. The leaf size was also improved by the pulegone, which did not affect the morphological changes of the roots. Conclusion: Our results suggest that the use of pulegone is a viable treatment to mitigate the effects of salt stress on A. cepa seeds.

Anacardium occidentale (Anacardiaceae), popularly known as cashews, is a vegetable native to South America, consumed worldwide in the food sector. Its leaves and bark are used in the preparation of teas for health maintenance, being indicated in ethnobotanical studies for the treatment of cancer, which is considered a serious public health problem worldwide. The objective of this study was to evaluate the cytotoxicity of the A. occidentale leaf and bark extracts over tumor and normal cells, as well as their in vivo toxicity using the Drosophila melanogaster fruit fly. Cytotoxicity was evaluated using the MTT method [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazol bromide] in five cell lines (HL-60, NCI-H292, HCT-116, P815 and L929). Toxicity was evaluated by fly mortality rate and negative geotaxis, as well as by oxidative stress markers (Fe2+ quantification, protein and non-protein thiols) in the D. melanogaster model. The chromatographic study was performed by UPLC-QTOF/MS. As a result, 11 compounds present in the A. occidentale leaf extract (LEAo) and 6 compounds in the bark extract (BEAo) were identified, with gallic acid and galloyl hexoside being present in both samples. The bark extract presented a greater cytotoxic activity for HCT-116, HL60 and P815 tumor cells. The extracts also presented a low cytotoxicity with the normal cell line, L929. No changes in the levels of protein and non-protein thiols (NPSH) were observed, whereas a considerable increase in Fe2+ levels was observed in the Fe2+ quantification assays from homogenized flies exposed to the leaf extract in the D. melanogaster assays. However, further in-depth studies need to be carried out to elucidate the mechanisms of action of the extracts and to assess their pharmacological safety.

Weeds are an important source of natural products; with promising biological activity. This study investigated the anti-kinetoplastida potential (in vitro) to evaluate the cytotoxicity (in vitro) and antioxidant capacity of the essential oil of

Thiazolidine compounds NJ20 {(E)-2-(2-(5-bromo-2-methoxybenzylidene)hydrazinyl)-4-(4-nitrophenyl)thiazole} and NW05 [(2-(benzo (d) (1,3) dioxol-4-ylmethylene)-N-(4-bromophenyl)-thiosemicarbazone] potentiated the effect of norfloxacin in resistant bacteria; however, there are no reports on their effects on

The microorganism resistance to antibiotics has become one of the most worrying issues for science due to the difficulties related to clinical treatment and the rapid spread of diseases. Efflux pumps are classified into six groups of carrier proteins that are part of the different types of mechanisms that contribute to resistance in microorganisms, allowing their survival. The present study aimed to carry out a bibliographic review on the superfamilies of carriers in order to understand their compositions, expressions, substrates, and role in intrinsic resistance. At first, a search for manuscripts was carried out in the databases Medline, Pubmed, ScienceDirect, and Scielo, using as descriptors: efflux pump, expression, pump inhibitors and efflux superfamily. For article selection, two criteria were taken into account: for inclusion, those published between 2000 and 2020, including textbooks, and for exclusion, duplicates and academic collections. In this research, 139,615 published articles were obtained, with 312 selected articles and 7 book chapters that best met the aim. From the comprehensive analysis, it was possible to consider that the chromosomes and genetic elements can contain genes encoding efflux pumps and are responsible for multidrug resistance. Even though this is a well-explored topic in the scientific community, understanding the behavior of antibiotics as substrates that increase the expression of pump-encoding genes has challenged medicine. This review study succinctly summarizes the most relevant features of these systems, as well as their contribution to multidrug resistance.

Mercury chloride (HgCl

Cymbopogon winterianus, known as “citronella grass”, is an important aromatic and medicinal tropical herbaceous plant. The essential oil of C. winterianus (EOCw) is popularly used to play an important role in improving human health due to its potential as a bioactive component. The present study aimed to identify the components of the essential oil of C. winterianus and verify its leishmanicidal and trypanocidal potential, as well as the cytotoxicity in mammalian cells, in vitro. The EOCw had geraniol (42.13%), citronellal (17.31%), and citronellol (16.91%) as major constituents. The essential oil only exhibited significant cytotoxicity in mammalian fibroblasts at concentrations greater than 250 μg/mL, while regarding antipromastigote and antiepimastigote activities, they presented values considered clinically relevant, since both had LC50 < 62.5 μg/mL. It can be concluded that this is a pioneer study on the potential of the essential oil of C. winterianus and its use against the parasites T. cruzi and L. brasiliensis, and its importance is also based on this fact. Additionally, according to the results, C. winterianus was effective in presenting values of clinical relevance and low toxicity and, therefore, an indicator of popular use.

In recent decades, fungal infections have been increasing, as well as the indiscriminate use of large-scale antifungal. The objective of the present study was to characterize the chemical components of L. montevidensis leaf essential oil (EOLm) and evaluate its antifungal potential and fluconazole modulating activity against Candida strains. The essential oil was obtained by hydrodistillation and its chemical components were determined by Gas Chromatography coupled to Mass Spectrometry. The antifungal activity was determined by the microdilution method to determine the minimum inhibitory concentration. The modulatory activity of fluconazole by the oil (EOLm) was evaluated against the four Candida strains. Our results demonstrated a predominance of β-Caryophyllene (34.96%) and Germacrene D (25.49%), while (E)-Caryophyllene (0.08%) and δ-Cadinene (0.13%) were the minor constituents. For the antifungal activity, it was evidenced that the EOLm did not inhibit the growth of Candida albicans (CA LM 77 and CA INQS 40006) and Candida tropicalis (CT INCQS 40042 and CT LM 23), but, potentiated the effect of fluconazole in particular against C. tropicalis, although the FIC index indicates indifferent modulation for all strains tested. This study strongly suggests that administration of the fluconazole in combination with plant essential oils can provide a new opportunity to improve the outcome of the drug effect.

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.

Some species of the genus Miconia are used in Brazilian folk medicine as analgesic and anti-inflammatory; however, several species of this genus are still poorly studied. Therefore, the aims of this study were to investigate the phytochemistry characterization by UPLC-DAD-QTOF-MS/MS, acute toxicity, anti-inflammatory and antinociceptive properties of Miconia minutiflora (Bonpl.) DC. The methanol extract of M. minutiflora (Mm-MeOH) was subjected to ultra-high-performance liquid chromatography (UPLC-DAD-QTOF-MS/MS) for the identification of the main phytocompounds. The anti-inflammatory properties of the extracts were studied using several inflammation models induced by carrageenan and acetic acid-induced vascular permeability. Antinociceptive effects of Mm-MeOH were assessed in nociception induced by intraperitoneal acetic acid or subplantar formalin injection. The role of α-adrenergic, cholinergic, and opioid receptors in modulating the extract's antinociceptive activity was determined. Analyses by UPLC-DAD-QTOF-MS/MS revealed the presence of ellagic acid, gallotannin, and terpenes in the methanol extract. Mm-MeOH (100 mg/kg) reduced carrageenan-induced paw edema and vascular permeability and inhibited leukocyte migration toward the air pouch and pleural cavity. Furthermore, Mm-MeOH decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels. Administration of Mm-MeOH reduced the number of writhes by 58.9% and increased the pain threshold in the formalin test. The anti-inflammatory action mechanism of Mm-MeOH is associated with inhibition of proinflammatory cytokines TNF-α and IL-1β, whereas the antinociceptive actions involve peripheral and central mechanisms with participation of α2-adrenergic receptors. These effects may be attributed to the presence of polyphenolics in the extract.

Mercury chloride (HgCl2) acts as a bioaccumulator capable of causing numerous neurological and physiological changes in organisms in a negative way. However, rutin has been considered a very effective antioxidant compound in the treatment of neurodegenerative diseases, as it can neutralize radicals capable of damaging neuronal cells. In this context, this study aimed to evaluate rutin as a neoprotective agent against the damage induced by HgCl2 in Drosophila melanogaster. The exposure of the flies to the agents was carried out in triplicate, and about 150 adult flies were evaluated. To assess the antioxidant action of rutin, MTT, phenanthroline, nitric oxide, total thiols and NPSH tests were carried out in the following concentrations: Control (1500 μL of distilled water), 1 mg/g of HgCl2, 0.5 mg/g of Rutin + HgCl2, 1 mg/g of Rutin + HgCl2, 2 mg/g of Rutin + HgCl2. The locomotion test was verified by negative geotaxis, the result of which showed that flies exposed to HgCl2 had difficulties in flight. The group treated with HgCl2 alone had a high mortality rate, while in combination with different concentrations of rutin, it heard a moderate reduction in the number of deaths, as well as in the negative geotaxis data in which the rutin had a positive effect. An increase in iron (II) levels was observed at the highest concentrations of rutin, while at low concentrations, rutin significantly decreased nitric oxide levels. The HgCl2 + R group (2 mg/g) showed a significant increase in the total thiols content, while for the NPSH all rutin concentrations showed a significant increase in the levels of non-protein thiols. Our results demonstrate that mercury chloride can cause oxidative stress in D. melanogaster. However, the results suggest that rutin has antioxidant and protective effects against the damage caused by HgCl2.

Compounds capable of inhibiting the efflux pump mechanism are a promising alternative against bacterial resistance because, when combined with antibiotics, they can increase the effectiveness of these drugs by inhibiting active efflux. Elaiophylin, derived from Streptomyces hygroscopicus, is a natural antibiotic that exhibits a variety of biological activities, including antibacterial activity. However, its potential as an inhibitor of the bacterial efflux mechanism has not been investigated. This study evaluated the ability of Elaiophylin to inhibit the NorA efflux pump in Staphylococcus aureus strains. Therefore, tests were performed to obtain the Minimum Inhibitory Concentration (MIC) and to verify the ability of Elaiophylin to potentiate the MIC of the antibiotic Norfloxacin and Ethidium Bromide (EtBr), known substrates of NorA efflux. Real-time PCR and molecular docking assays were also performed to assess the potential of Elaiophylin against NorA. The strains SA-1199 (wild type) and SA-1199B (NorA over-expressed) of S. aureus were used for this study. The results showed that Elaiophylin significantly decreased the MIC of Norfloxacin and EtBr, increasing the activity of these substrates against S. aureus, which carries the efflux protein NorA. However, Elaiophylin provided a non-significant reduction in norA gene expression, however, molecular docking demonstrated a high binding affinity between Elaiophylin and NorA efflux protein, indicating that Elaiophylin can act as a potential NorA in S. aureus.

The barks of Anacardium occidentale (cashew tree) been used for centuries in the popular pharmacopoeia of South America and West Africa for the treatment of infections and neurodegenerative diseases. Thus, this work aimed to evaluate the biological effect of the ethanolic extract of the barks against strains of Candida spp. and cancer cell lines, as well as identifying the chemical constituents present in the product. For that, the extract was submitted to an UPLC-QTOF/MS, which mass fragments were compared in the literature at the botanical family level. For antifungal activity, the serial microdilution method was used in varying concentrations, and the modifier of fluconazole in sub-inhibitory concentrations (CFM/16). Cytotoxicity was evaluated using the MTT method [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazol bromide] in five cell lines (HL-60, NCI-H292, HCT-116, P815 and L929). Eight compounds were identified, including gallic acid, luteolin, epicatechin gallate and agathisflavone. An antifungal effect of the extract was observed for the strains of Candida albicans, Candida krusei and Candida tropicalis, with IC50 lower than 400 μg/mL. In addition, there was a synergistic action with fluconazole against C. albicans and C. tropicalis. As for antitumor activity, there was a moderate activity against all cancer lines, showing low cytotoxicity for the normal line, making the extract an excellent candidate for drug development. The ethnopharmacological use of A. occidentale by populations for the treatment of DIP’s and neurodegenerative diseases, reveal that this organ has biological actions against microorganisms that cause infections, as well as being capable of causing toxicity in cancer cells.

Bacteria of Streptomyces genus are a promising source of biologically active products, with applications in medicine, industry and agriculture. Therefore, the objective of this work was to evaluate the cytotoxic, antioxidant and antimicrobial activities of fermented rice extract and their semipurified fractions from Streptomyces spp. isolated of the rhizosphere of Paullinia cupana, Amazon-Brazil. For this, a bioguided study was carried out by the cytotoxic activity with methanolic extract of Streptomyces sp. ACTMS-12H UFPEDA 3405 (EMeOH-12H) partitioned with n-hexane, ethyl acetate and 2-butanol. The antioxidant activity was analyzed using the DPPH, ABTS and phosphomolybdenum methods, while the antimicrobial activity was investigated by microdilution method to determine the minimum inhibitory concentration (MIC) against species of bacteria and yeast. In the cytotoxicity test, the butanolic phase (FbuOH-12H) presented IC50 of 1.1 µg/mL against MOLT-4, with cell death probably by apoptosis, but did not cause cytotoxicity on peripheral blood mononuclear cell (PBMC) or human erythrocytes. Chemical prospecting detected the presence of saponins and reducing sugars on 2-butanol fraction (FBuOH-12H), which can be related to cytotoxicity. On the antioxidant activity by ABTS, the partition with ethyl acetate (FAcOEt-12H) showed antioxidant capacity of 1161.7 ± 0.04 µM of Trolox/g of extract, indicating an expressive reactivity of the phase with this radical. The aqueous phases (from hexane, ethyl acetate and methanol extracts) were active in all tested microorganisms, except E. faecalis. Las bacterias del género Streptomyces son una fuente prometedora de productos biológicamente activos, con aplicaciones en medicina, industria y agricultura. Por lo tanto, el objetivo de este trabajo fue evaluar las actividades citotóxicas, antioxidantes y antimicrobianas de los extractos y fracciones semipurificadas de Streptomyces spp. aislada de la rizósfera de Paullinia cupana, Amazonas-Brasil. Para ello, se realizó un estudio bioguiado de la actividad citotóxica con extracto metanólico de Streptomyces sp. El extracto ACTMS-12H UFPEDA 3405 (EMeOH-12H) fue fraccionado con n-hexano, acetato de etilo y 2-butanol. La actividad antioxidante fue analizada a través de los métodos de DPPH, ABTS y fosfomolibdeno, mientras que la actividad antimicrobiana fue investigada por el método de microdilución para determinar la concentración minima inhibitoria (MIC) contra especies de bacterias y levaduras. En la prueba de citotoxicidad la fase butanólica (FbuOH-12H) presentó una IC50 de 1.1 µg/mL contra MOLT-4, con muerte celular probablemente por apoptosis, pero no causó citotoxicidad en las células mononucleares de sangre periférica (PBMC) o en eritrocitos humanos, La prospección química detectó la presencia de saponinas y azúcares reductores en la fracción de 2-butanol (FBuOH-12H), que pueden estar relacionados con la citotoxicidad. Sobre la actividad antioxidante por ABTS, la fracción de acetato de etilo (FAcOEt-12H) mostró una capacidad antioxidante de 1161.7 ± 0.04 µM de Trolox/g de extracto, indicando una expresiva reactividad de la fase con este radical. Las fases acuosas (de los extractos de hexano, acetato de etilo y metanol) fueron activas en todos los microorganismos probados, excepto E. faecalis. As bactérias de gênero Streptomyces são fontes promissoras de produtos biologicamente ativos, com aplicações na medicina, indústria e agricultura. Portanto, o objetivo deste trabalho foi avaliar as atividades citotóxica, antioxidante e antimicrobiana do extrato fermentado em arroz e suas frações semipurificadas de Streptomyces spp. isolado da rizosfera de Paullinia cupana, Amazônia, Brasil. O estudo bioguiado foi realizado através da atividade citotóxica com o extrato metanólico de Streptomyces sp. ACTMS-12H UFPEDA 3405 (EMeOH-12H) particionado com n-hexano, acetato de etila e 2-butanol. A atividade antioxidante foi analizada pelos métodos do DPPH, ABTS e fosfomilibidênio, enquanto que a atividade antimicrobiana foi feita pelo método da microdiluição para determinar a concentração inibitória minima (MIC) frente a espécies de bactérias e levedura. No teste de citotoxicidade, a fase butanólica (FbuOH-12H) apresentou IC50 de 1,1 µg/mL frente à linhagem MOLT-4, com morte celular provavelmente por apoptose, mas não causou citotoxicidade em células mononucleares do sangue periférico (PBMC) nem em eritrócitos humanos. A prospecção fitoquímica detectou a presença de saponinas e açúcares redutores na fração 2-butanol (FBuOH-12H), e estes compostos podem estar relacionados à citotoxicidade. Na atividade antioxidante pelo ABTS, a partição com acetato de etila (FAcOEt-12H) apresentou capacidade antioxidante de 1161,7 ± 0,04 µM de Trolox/g do extrato, indicando uma expressiva reatividade da fase com este radical. A fase aquosa (dos extratos hexano, acetate de etila e metanol) foi ativa para todos os microrganismos testados, exceto E. faecalis.

Thiazol and thiazolidinedione derivatives are known in the literature for presenting several biological activities, such as anti-diabetic, anti-inflammatory, antiparasitic, antifungal and antimicrobial activity. With this in mind, this study reports on the synthesis and antibacterial activity of thiazole (NJ) and thiazolidinedione (NW) derivatives, as well as their effects in association with norfloxacin, against NorA efflux pumps in the Staphylococcus aureus 1199B (SA-1199B) strain. Among the 14 compounds evaluated, 9 were found to potentiate norfloxacin activity, with 4 compounds from the NJ series promoting a threefold norfloxacin MIC reduction. Molecular docking assays were used to confirm the binding mode of most active compounds. In the in silico study, the efficiency of the interaction of NJ series compounds with the NorA pump were evaluated. Derivatives from both series did not show considerable intrinsic antibacterial activity (MIC ˃ 1024 μg/mL) against any of the tested strains. However, the NJ16 and NJ17 compounds, when associated with norfloxacin, reduced the MIC of this drug threefold and inhibited NorA pumps in the 1199B strain. Moreover, some NW (05, 10, 18, 19 and 21) and NJ compounds (16, 17, 18 and 20) presented low to moderate cytotoxicity against normal cells. Molecular docking studies supported the potent in vitro inhibitory activity of NJ16 and NJ17, which showed NJ16 and NJ17 possessed more favorable binding energies of -9.03 Kcal/mol and -9.34 Kcal/mol, respectively. In addition, NJ16 showed different types of interactions involved in complex stabilization. In conclusion, NJ16 and NJ17, in combination with norfloxacin, were able to completely restore the antibacterial activity of norfloxacin against S. aureus SA-1199B, the norA-overexpressing strain, with low cytotoxicity in normal cells.

Paraquat (PQ) is a widely used herbicide with no antidote which is implicated in the pathogenesis of the Parkinson's disease. The present study then investigated the potential of caffeic acid (CA), a known antioxidant, cardioprotective and neuroprotective molecule to counteract oxidative stress mediated by PQ. In addition, molecular docking was performed to understand the mechanism underlying the inhibitory effect of CA against PQ poisoning. The fruit fly, Drosophila melanogaster, was exposed to PQ (0.44 mg/g of diet) in the absence or presence of CA (0.25, 0.5, 1 and 2 mg/g of died) for 7 days. Data showed that PQ-fed flies had higher incidence of mortality which was associated with mitochondrial dysfunction, increased free Fe(II) content and lipid peroxidation when compared to the control. Co-exposure with CA reduced mortality and markedly attenuated biochemical changes induced by PQ. The mechanism investigated using molecular docking revealed a strong interaction (−6.2 Kcal/mol) of CA with D. melanogaster transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2). This was characterized by the binding of CA to keap-1 domain of Nrf2. Taking together these results indicate the protective effect of CA against PQ-induced oxidative damage in D. melanogaster was likely through its coordination which hinders Nrf2-keap-1 binding leading to an increase of the antioxidant defense system.

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.

Staphylococcus aureus is a Gram-positive bacterium responsible for a number of diseases and has demonstrated resistance to conventional antibiotics. This study aimed to evaluate the antibacterial activity of eugenol and its derivatives allylbenzene, 4-allylanisole, isoeugenol and 4-allyl-2,6-dimethoxyphenol against the S. aureus NorA efflux pump (EP) in association with norfloxacin and ethidium bromide. The antibacterial activity of the compounds was assessed using the broth microdilution method to determine the minimum inhibitory concentration (MIC). A reduction in the MIC of ethidium bromide (a substrate for several efflux pumps) or norfloxacin was used as a parameter of EP inhibition. Molecular modeling studies were used to predict the 3D structure and analyze the interaction of selected compounds with the binding pocket of the NorA efflux pump. Except for 4-allylanisole and allylbenzene, the compounds presented clinically effective antibacterial activity. When associated with norfloxacin against the SA 1199B strain, 4-allyl-2,6-dimethoxyphenol eugenol and isoeugenol caused significant reduction in the MIC of the antibiotic, demonstrating synergistic effects. Similar effects were observed when 4-allyl-2,6-dimethoxyphenol, allylbenzene and isoeugenol were associated with ethidium bromide. Together, these findings indicate a potential inhibition of the NorA pump by eugenol and its derivatives. This in vitro evidence was corroborated by docking results demonstrating favorable interactions between 4-allyl-2,6-dimetoxypheno and the NorA pump mediated by hydrogen bonds and hydrophobic interactions. In conclusion, eugenol derivatives have the potential to be used in antibacterial drug development in strains carrying the NorA efflux pump.

Turismo religioso, Pe. Cicero e desenvolvimento sao os temas imbricados neste estudo. As peregrinacoes e romarias sao marcas importantes do turismo religioso de Juazeiro do Norte, que sofreu forte influencia do seu fundador, o Padre Cicero. O objetivo deste trabalho e mostrar a questao da religiosidade e o crescimento da cidade de Juazeiro do Norte, atraves da influencia do Padre Cicero, relacionando a sua influencia sobre o crescimento economico da cidade. Para realizacao desta pesquisa foram feitas entrevistas, consulta e analise de documentos e publicacoes referentes ao turismo religioso em Juazeiro do Norte. A partir desta pesquisa, constatou-se que a cidade de Juazeiro do Norte desde a sua fundacao cresceu em detrimento da presenca do seu fundador, o Padre Cicero. Consequentemente o turismo religioso sofreu a mesma, do “Padim Cico”, cuja memoria impulsiona o crescimento economico da cidade.

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.

Chrysobalanus icaco L. is a native plant of Brazil used as a food source and traditionally for the treatment of various diseases. The aim of study was performed the phytochemical analysis by UPLC-DAD-ESI-QTOF-MS/MS, and evaluated acute and repeated dose oral toxicities of the C. icaco L. leaf aqueous extract (AECi). The acute toxicity study was performed using a dose of AECi 2000 mg/kg, while the repeated dose toxicity study, the AECi was administered daily at doses of 100, 200 and 400 mg/kg, for 28 days. Behavior and mortality of animals were observed during the test period and body weight, as well water and eating consumption. Hematological, biochemical parameters and histopathological examinations were carried out. Phytochemical analysis of the AECi revealed the presence of flavonoids and tannins. Oral single dose of 2000 mg/kg of AECi resulted in no mortalities or abnormal clinical signs. Studies of repeated dose toxicity promoted a reduction in the body weight of treated animals and an increase of hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in both, males and females. Histopathological analyzes showed alterations in the livers of animals treated with AECi. Thus, this study recommends the population take care when using this species, especially during prolonged periods.

This study was carried out to test the essential oil from C. ambrosioides leaves and its main constituent, α-Terpinene, in an antibacterial activity assay. As well, it was evaluated ability reduce resistance to norfloxacin and ethidium bromide was compared the Staphylococcus aureus 1199B whith 1199 wild type strain. The MIC of the C. ambrosioides essential oil and α-Terpinene were determined by microdilution method. The MIC of the essential oil and α-Terpinene presented a value ≥ 1024 μg/mL. However, when associated with antibacterials, the essential oil from C. ambrosioides leaves significantly reduced the MIC of antibiotics and ethidium bromide, characterizing an efflux pump inhibition. The C. ambrosioides essential oil, despite having no direct antibacterial activity against the S. aureus 1199B strain, showed a potentiating action when associated with antibacterial agents, this being attributed to an inhibition of efflux pumps.

O presente trabalho teve como objetivo estudar simultaneamente as contribuicoes da sucupira-branca (Pterodon emarginatus Vogel) e da etnologia, evidenciando as interacoes com a comunidade rural do municipio de Jardim-CE. A area estudada foi o Cariri cearense inserida na Floresta Nacional do Araripe, uma regiao rica em biodiversidade e potencial. Durante as ultimas decadas os avancos tecnologicos possibilitaram a descoberta de diversas especies de uso medicinal. Boa parte dessas descobertas deveu-se ao conhecimento popular, contribuindo com a etnobotânica no campo de pesquisa. A pesquisa foi realizada nos meses entre fevereiro e maio de 2014. Os resultados demonstraram que a sucupira-branca possui um grande potencial para producao de fitoterapicos. Segundo os relatos da comunidade, a especie e muito utilizada na medicina caseira, porem, ainda sao desconhecidas as suas contra-indicacoes.

A maioria das cidades enfrenta grandes problemas, como poluicao dos rios, falta de saneamento, entre outros. Hoje tem se buscado uma melhoria na qualidade de vida e ambiental. A qualidade ambiental por sua vez relaciona-se com a melhoria do modo de vida, tornando-se importante o despertar da comunidade para uma percepcao ambiental voltada para a conservacao do ambiente em que vive. A presente pesquisa foi realizada com os moradores do entorno do Rio Carius. O objetivo foi investigar a percepcao dos moradores do entorno do rio Carius em relacao ao mesmo. Para a pesquisa foi utilizada uma abordagem qualitativa, com elementos quantitativos, sendo empregado um questionario semiestruturados, onde foram abordados de forma aleatoria, cem moradores da localidade. Os dados foram tabulados no Excel. De acordo com a pesquisa 53% era do sexo feminino; 17% sabiam o que eram educacao ambiental; 58% afirmaram que meio ambiente e definido como natureza e ainda responderam que a forma de melhorar a vida do rio seria a cidade ter um sistema saneamento basico (27%) e ser desenvolvido de um programa de educacao ambiental para minimizar os impactos ambientais e uma forma de conscientizar a populacao.