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1.
Microb Pathog ; 180: 106129, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37119940

RESUMO

The increased resistance of microorganisms to antimicrobial drugs makes it necessary to search for new active compounds, such as chalcones. Their simple chemical structure makes them molecules easy to synthesize. Therefore, the aim of this study was to evaluate the antimicrobial and potentiating activity of antibiotics and antifungals by synthetic chalcones against strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Candida tropicalis. The synthesis of chalcones was carried out by Claisen-Schimidt aldol condensation. Nuclear Magnetic Resonance (NMR) and Gas Chromatography Coupled to Mass Spectrometry (GC/MS) were also performed. Microbiological tests were performed by the broth microdilution method, using gentamicin, norfloxacin and penicillin as standard drugs for the antibacterial assay, and fluconazole for the antifungal assay. Three chalcones were obtained (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one (DB-Acetone), (1E,3E,6E,8E)-1,9-diphenylnone-1,3,6,8-tetraen-5-one (DB-CNM), (1E,4E)-1,5-bis (4-methoxyphenyl) penta-1,4-dien-3-one (DB-Anisal). The compound DB-Acetone was able to inhibit P. aeruginosa ATCC 9027 at a concentration of 1.4 × 102 µM (32 µg/mL), while DB-CNM and DB-Anisal inhibited the growth of S. aureus ATCC 25923 at 17.88 × 102 µM and 2.71 × 101 µM (512 µg/mL and 8 µg/mL) respectively. In the combined activity, DB-Anisal was able to potentiate the effect of the three antibacterial drugs tested against E. coli 06, norfloxacin (128 for 4 µg/mL ±1) against P. aeruginosa 24 and penicillin (1,024 for 16 µg/mL ±1) against S. aureus 10. In antifungal assays, chalcones were not able to inhibit the growth of fungal strains tested. However, both showed potentiating activity with fluconazole, ranging from 8.17 x 10-1 µM (0.4909 µg/mL) to 2.35 µM (13.96 µg/mL). It is concluded that synthetic chalcones have antimicrobial potential, demonstrating good intrinsic activity against fungi and bacteria, in addition to potentiating the antibiotics and antifungal tested. Further studies are needed addressing the mechanisms of action responsible for the results found in this work.


Assuntos
Anti-Infecciosos , Chalconas , Antifúngicos/química , Fluconazol/farmacologia , Chalconas/farmacologia , Chalconas/química , Staphylococcus aureus , Norfloxacino/farmacologia , Escherichia coli , Acetona/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/química , Candida albicans , Penicilinas/farmacologia , Testes de Sensibilidade Microbiana
2.
Biofouling ; : 1-10, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597191

RESUMO

This work investigates the ability of two Croton spp. essential oils (EO) to enhance chlorhexidine (CHX) activity against oral streptococci. EO's chemical composition of Croton argyrophyllus and C. pluriglandulosus was determined by GC-MS/FID. The microbial growth kinetics and minimum inhibitory concentration (MIC) of EOs and CHX were determined, followed by their synergism against S. mutans UA159 and ATCC 25175, S. salivarius ATCC 7073 and S. sp. ATCC 15300. The microplate-based method was used to determine the EO/CHX activity against 24-h-old biofilms. The major compounds were α-pinene (54.74%) and bicyclogermacrene (16.08%) for EOAr and 1,8-cineole (17.41%), methyleugenol (16.06%) and elemicin (15.99%) for EOPg. Both EO had MIC around 16,000 µg/mL. EOs/CHX presented a synergistic effect against most strains (FICi from 0.133 to 0.375), and OE/CHX-treated biofilms showed a reduction in biomass and cell viability compared to CHX, only (p < 0.01). Thus, the EOs works as natural adjuvants for CHX.

3.
Biochem Biophys Res Commun ; 537: 71-77, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33387885

RESUMO

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.


Assuntos
Acetamidas/química , Acetamidas/farmacologia , Enzima de Conversão de Angiotensina 2/química , Antivirais/farmacologia , Chalcona/análogos & derivados , Proteases 3C de Coronavírus/química , Simulação de Acoplamento Molecular , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/química , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/química , Chalcona/química , Chalcona/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Humanos , Testes de Sensibilidade Microbiana , SARS-CoV-2/química , SARS-CoV-2/enzimologia , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/metabolismo , Replicação Viral/efeitos dos fármacos
4.
Biochem Biophys Res Commun ; 534: 478-484, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33261884

RESUMO

Croton zehntneri is a plant known as canelinha de cunhã, 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.


Assuntos
Analgésicos/farmacologia , Nociceptividade/efeitos dos fármacos , Ácidos Palmíticos/farmacologia , Triterpenos/farmacologia , Analgésicos/química , Animais , Córnea/efeitos dos fármacos , Córnea/fisiologia , Croton/química , Modelos Moleculares , Ácidos Palmíticos/química , Triterpenos/química , Peixe-Zebra/fisiologia
5.
Microb Pathog ; 155: 104894, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33894291

RESUMO

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.


Assuntos
Chalcona , Chalconas , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Chalconas/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Norfloxacino/farmacologia , Staphylococcus aureus/metabolismo
6.
Microb Pathog ; 156: 104934, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33962005

RESUMO

The aim of this work was to evaluate the chemical composition and antibacterial activity of Croton tetradenius Baill. (CTEO) and C. pulegiodorus Baill. (CPEO) essential oils against Staphylococcus aureus, and their synergism with antibiotics. The essential oils (EOs) were extracted by hydrodistillation and chemically characterized by gas chromatography-mass spectrometry (CG-MS) and gas chromatography with flame ionization detection (CG-FID). The antimicrobial action of the EOs was tested against two standard strains and four clinical isolates of S. aureus using the disk-diffusion agar method and the microdilution assay. The bacterial kinetic growth was also determined. The synergistic effect between EOs and antimicrobials was analyzed by the checkerboard test. CTEO and CPEO yielded 0.47 and 0.37% w/w and the most common components were p-cymene (28.24%), camphor (17.76%) and α-phellandrene (8.98%), and trans-chrysanthenyl acetate (27.05%), α-terpinene (19.21%) and p-cymene (12.27%), respectively. The disk-diffusion test showed that the bacteria are sensitive to the agents tested. The MIC in the presence of the CTEO it was 4000 µg/mL, while for the CPEO it was 8000 µg/mL, except for clinical isolate 4B. The MBC for strains treated with CTEO were 8000 µg/mL, with the exception of isolates 8B and 0 A 4000 µg/mL. For the CPEO, all strains showed a concentration above 8000 µg/mL. The growth curve showed that CTEO and CPEO altered growth kinetics, delaying the lag phase and reducing the log phase. In combination with antibiotics, both essential oils showed synergisms effect with oxacillin and ampicillin, and additive effect with benzylpenicillin. CTEO and CPEO showed antibacterial action against S. aureus strains, showing as a promise natural alternative in clinical therapy.


Assuntos
Anti-Infecciosos , Croton , Óleos Voláteis , Antibacterianos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia , Staphylococcus aureus
7.
Arch Microbiol ; 204(1): 63, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34940944

RESUMO

The Staphylococcus aureus bacteria is a Gram-positive, immobile, non-spore bacterium, with catalase and positive coagulase, among other characteristics. It is responsible for important infections caused in the population and for hospital infections. Because of that many strategies are being developed to combat the resistance of microorganisms to drugs, in recent times, chalcones have been studied for this purpose. Chalcones are found in parts of plants and can be found, for example, in the roots, leaves, bark, among others, but are mainly found as petal pigments, they are a class of compounds considered an exceptional model due to chemical simplicity and a wide variety of biological activities. This study aimed to evaluate the ability of chalcone (E)-3-(2,4-dichlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one to reverse the efflux pump resistance, present in the bacteria S. aureus 1199B and S. aureus K2068. The synthetic chalcone (E)-3-(2,4-dichlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one was able to synergistically modulate the antibiotic Ciprofloxacino and Ethidium Bromide against the bacterial strain S. aureus K2068, and with the antibiotic Norfloxacino against the strain 1199B. Thus, it is suggested that this chalcone may be acting by inhibiting the efflux pump mechanism of these bactéria. The theoretical physicochemical and pharmacokinetic properties of chalcone showed that the chalocne did not present a severe risk of toxicity, such as genetic mutation or cardiotoxicity. Molecular docking showed that the chalcone could act as a competitive inhibitor of the MepA efflux pump, as at hinders the binding of other substrates, such as EtBr.


Assuntos
Chalcona , Chalconas , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Chalcona/farmacologia , Chalconas/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Staphylococcus aureus/metabolismo
8.
Epilepsy Behav ; 117: 107881, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33711684

RESUMO

In the treatment of anxiety and seizures, drugs of the benzodiazepine (BZD) class are used, which act on the Central Nervous System (CNS) through the neurotransmitter gamma-aminobutyric acid (GABA). Flavonoids modulate GABAA receptors. The aim of this study was to evaluate the anxiolytic and anticonvulsant effects of synthetic chalcones and their mechanisms of action via the GABAergic system, using adult zebrafish (ZFa). The animals were treated with chalcones (4.0 or 20 or 40 mg/kg; 20 µL; i.p) and submitted to the open field and 96 h toxicity test. Chalcones that cause locomotor alteration were evaluated in the light and dark anxiolytic test. The same doses of chalcones were evaluated in the anticonvulsant test. The lowest effective dose was chosen to assess the possible involvement in the GABAA receptor by blocking the flumazenil (fmz) antagonist. No chalcone was toxic and altered ZFa's locomotion. All chalcones had anxiolytic and anticonvulsant effects, mainly chalcones 1, where all doses showed effects in both tests. These effects were blocked by Fmz (antagonist GABAA), where it shows evidence of the performance of these activities of the GABA system. Therefore, this study demonstrated in relation to structure-activity, that the position of the substituents is important in the intensity of activities and that the absence of toxicity and the action of these compounds in the CNS, shows the pharmacological potential of these molecules, and, therefore, the insights are designed for the development of new drugs.


Assuntos
Ansiolíticos , Chalconas , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Comportamento Animal , Chalconas/uso terapêutico , Receptores de GABA-A , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Peixe-Zebra
9.
Biochem Biophys Res Commun ; 533(3): 362-367, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-32962857

RESUMO

Drugs used to treat pain are associated with adverse effects, increasing the search for new drugs as an alternative treatment for pain. Therefore, we evaluated the antinociceptive behavior and possible neuromodulation mechanisms of triterpene 3ß, 6ß, 16ß-trihydroxylup-20(29)-ene (CLF-1) isolated from Combretum leprosum leaves in zebrafish. Zebrafish (n = 6/group) were pretreated with CLF-1 (0.1 or 0.3 or 1.0 mg/mL; i.p.) and underwent nociception behavior tests. The antinociceptive effect of CFL-1 was tested for modulation by opioid (naloxone), nitrergic (L-NAME), nitric oxide and guanylate cyclase synthesis inhibitor (methylene blue), NMDA (Ketamine), TRPV1 (ruthenium red), TRPA1 (camphor), or ASIC (amiloride) antagonists. The corneal antinociceptive effect of CFL-1 was tested for modulation by TRPV1 (capsazepine). The effect of CFL-1 on zebrafish locomotor behavior was evaluated with the open field test. The acute toxicity study was conducted. CLF-1 reduced nociceptive behavior and corneal in zebrafish without mortalities and without altering the animals' locomotion. Thus, CFL-1 presenting pharmacological potential for the treatment of acute pain and corneal pain, and this effect is modulated by the opioids, nitrergic system, NMDA receptors and TRP and ASIC channels.


Assuntos
Analgésicos/farmacologia , Combretum/química , Locomoção/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Dor/prevenção & controle , Triterpenos/farmacologia , Canais Iônicos Sensíveis a Ácido/metabolismo , Amilorida/farmacologia , Analgésicos/isolamento & purificação , Animais , Cânfora/farmacologia , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Ketamina/farmacologia , Locomoção/fisiologia , Masculino , Azul de Metileno/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Naloxona/farmacologia , Nociceptividade/fisiologia , Dor/metabolismo , Dor/fisiopatologia , Medição da Dor , Extratos Vegetais/química , Folhas de Planta/química , Receptores de N-Metil-D-Aspartato/metabolismo , Rutênio Vermelho/farmacologia , Canais de Cátion TRPV/metabolismo , Triterpenos/isolamento & purificação , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
10.
Biochem Biophys Res Commun ; 526(2): 505-511, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32241546

RESUMO

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.


Assuntos
Acetamidas/farmacologia , Ansiolíticos/farmacologia , Chalcona/farmacologia , Serotonina/metabolismo , Acetamidas/química , Animais , Ansiolíticos/química , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Chalcona/análogos & derivados , Descoberta de Drogas , Locomoção/efeitos dos fármacos , Simulação de Acoplamento Molecular , Receptores 5-HT1 de Serotonina/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
11.
Curr Microbiol ; 77(12): 3969-3977, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33025183

RESUMO

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.


Assuntos
Anti-Infecciosos , Óleos Voláteis , Vitex , Antibacterianos/farmacologia , Escherichia coli , Análise de Fourier , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia , Folhas de Planta , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus
12.
Microb Pathog ; 135: 103608, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31229603

RESUMO

This study aimed to determinate the chemical composition and evaluate the antimicrobial and antioxidant activity of the essential oil obtained from leaves of V. gardneriana. The Vitex gardneriana leaves's were hydrodistilled to obtain the essential oil and the chemical composition determined by GC/MS analysis. The antimicrobial activities were determined by microdilution method. The activity of essential oil on biofilm was evaluated by quantification of total biomass and enumeration of biofilm-entrapped viable cells. The antioxidant activity was assessed by DPPH free radical assay, ferrous ion chelating assay, ferric-reducing antioxidant power and ß-carotene bleaching assay. Furthermore, the essential oil was tested on viability of health human, animal cells and the microcrustacean Artemia sp. The essential oil showed high content of sesquiterpenes and very low content of monoterpenes. Regarding activity on planktonic cells, the essential oil reduced the growth of the all species tested but showed MIC values only to S. aureus (0.31%). In general, the essential oil reduced significantly the biofilm biomass and the number of viable cells of bacteria and yeasts, mainly on biofilm formation. The essential oil showed a potential antioxidant activity, mainly on ß-carotene oxidation. Moreover, the essential oil reduced the cell viability of murine fibroblasts but not show viability reduction of human keratinocytes. Furthermore, the oil not show toxicity against the microcrustacean. Thus, the essential oil from V. gardneriana leaves may be considered as an important alternative against biofilms formed by bacteria and yeasts related to infections, as well as a natural antioxidant and non-toxic substance on human cells.


Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Óleos Voláteis/química , Extratos Vegetais/química , Folhas de Planta/química , Vitex/química , Animais , Anti-Infecciosos/farmacologia , Artemia/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Brasil , Candida/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Monoterpenos/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , beta Caroteno
13.
Pharm Biol ; 53(3): 407-13, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25471298

RESUMO

CONTEXT: α- and ß-Amyrin (AMY) from Protium heptaphyllum (Aubl) March (Burseraceae) is found in Brazil and used in diverse inflammation-related diseases. This species presents a central action, as previously described. OBJECTIVE: The objectives were to evaluate the anticonvulsant effect of AMY in mice and to verify the mechanism of action. MATERIAL AND METHODS: Seizures were induced by pentylenetetrazole followed by acute or subchronic treatments (5-25 mg/kg, p.o. and i.p.) and determination of brain amino acids (10 and 25 mg/kg, i.p., 7 d). RESULTS: In the acute treatment, AMY (10, 25, and 50 mg/kg, p.o.) increased the latency to the first convulsion (FC) by 30, 44, and 40% and time to death (TD) by 36, 52, and 42%, respectively. When administered intraperitoneally, the same doses increased FC by 62, 75, and 73% and TD by 76, 82, and 119%, respectively. Combined with polymixin or staurosporine, AMY (25 mg/kg, i.p.) increased TD by 61 and 63%, respectively, as related to each drug alone. When subchronically administered (25 and 50 mg/kg, i.p.) increased FC by 75 and 101% and TD by 86 and 124%, respectively. AMY increased taurine (116 and 76%) and tyrosine concentrations (135 and 110%) in basal ganglia and hippocampus, respectively, and decreased by 68, 65, and 62% glutamate, aspartate, and GABA in basal ganglia. CONCLUSION: Thus, the AMY anticonvulsant activity is related to the GABAergic system and may be linked to the inhibition of the signaling cascade of PKC as well as to alterations in amino acids metabolism.


Assuntos
Aminoácidos/metabolismo , Anticonvulsivantes/uso terapêutico , Encéfalo/metabolismo , Burseraceae , Ácido Oleanólico/análogos & derivados , Proteína Quinase C/antagonistas & inibidores , Animais , Anticonvulsivantes/isolamento & purificação , Anticonvulsivantes/farmacologia , Encéfalo/efeitos dos fármacos , Masculino , Camundongos , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Proteína Quinase C/metabolismo , Inibidores de Proteínas Quinases/isolamento & purificação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Convulsões/tratamento farmacológico , Convulsões/patologia , Estereoisomerismo , Resultado do Tratamento
14.
Fundam Clin Pharmacol ; 38(1): 60-71, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37497790

RESUMO

BACKGROUND: The bacterium Staphylococcus aureus has stood out for presenting a high adaptability, acquiring resistance to multiple drugs. The search for natural or synthetic compounds with antibacterial properties capable of reversing the resistance of S. aureus is the main challenge to be overcome today. Natural products such as chalcones are substances present in the secondary metabolism of plants, presenting important biological activities such as antitumor, antidiabetic, and antimicrobial activity. OBJECTIVES: In this context, the aim of this work was to synthesize the chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one with nomenclature CMADMA, confirm its structure by nuclear magnetic resonance (NMR), and evaluate its antibacterial properties. METHODS: The synthesis methodology used was that of Claisen-Schmidt, and spectroscopic characterization was performed by NMR. For microbiological assays, the broth microdilution methodology was adopted in order to analyze the antibacterial potential of chalcones and to analyze their ability to act as a possible inhibitor of ß-lactamase and efflux pump resistance mechanisms, present in S. aureus strain K4100. RESULTS: The results obtained show that CMADMA does not show direct antibacterial activity, expressing a MIC of ≥1024 µg/mL, or on the enzymatic mechanism of ß-lactamase; however, when associated with ethidium bromide in efflux pump inhibition assays, CMADMA showed promising activity by reducing the MIC of the bromide from 64 to 32 µg/mL. CONCLUSION: We conclude that the chalcone synthesized in this study is a promising substance to combat bacterial resistance, possibly acting in the inhibition of the QacC efflux pump present in S. aureus strain K4100, as evidenced by the reduction in the MIC of ethidium bromide.


Assuntos
Chalcona , Chalconas , Staphylococcus aureus , Chalcona/farmacologia , Chalcona/metabolismo , Chalconas/farmacologia , Etídio/metabolismo , Etídio/farmacologia , beta-Lactamases/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
15.
J Biomol Struct Dyn ; 42(4): 1670-1691, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37222682

RESUMO

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


Assuntos
Chalcona , Chalconas , Nitrofenóis , Antibacterianos/química , Staphylococcus aureus , Norfloxacino/farmacologia , Norfloxacino/metabolismo , Simulação de Acoplamento Molecular , Chalcona/farmacologia , Chalconas/farmacologia , Testes de Sensibilidade Microbiana , Etídio/metabolismo , Proteínas de Bactérias/química , Proteínas Associadas à Resistência a Múltiplos Medicamentos
16.
Nat Prod Res ; 37(2): 333-337, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34338557

RESUMO

This study investigated the chemical composition and evaluated the antibacterial and antibiofilm activities of essential oils (EOs) extracted from Ruellia asperula (EORA) and Ruellia paniculata (EORP) against oral streptococci. The EO constituents were analyzed by gas chromatography/mass spectrometry. The antimicrobial potential of EOs was evaluated using the minimum inhibitory concentration, minimum bactericidal concentration, and time-kill determination. Furthermore, the quantification of total biomass and the number of viable cells in the biofilms were evaluated. The major constituents of EORA were cariophylla-4(12)-8-(13)-dien-5ß-ol (14.1%), (ß)-caryophyllene (22.7%), and caryophyllene oxide (29.4%). For EORP, the major constituents were (ß)-caryophyllene (11.0%), spathulenol (13.1%), and δ-amorphene (14.9%). The tested EOs exhibited antibacterial activity against planktonic growth and biofilm formation. Thus, the EOs from R. asperula and R. paniculata prove to be promising alternatives for bacterial growth control and biofilm formation prevention of oral streptococci.


Assuntos
Acanthaceae , Anti-Infecciosos , Óleos Voláteis , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana
17.
J Biomol Struct Dyn ; 41(13): 6434-6441, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35894999

RESUMO

Leishmaniasis disease is a serious public health problem. This disease reaches about 10 to 12 million people, and 20-30 thousand people die yearly. The disease treatment is realized through pentavalent antimonial and glucantime. However, some studies indicated that these drugs presented high toxicity and cost. Therefore, it is urgent the search for new drugs that may combat this disease and are less toxic. This work analyzed for the first time the interaction potential of (E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one (C1), (E)-1-(4-aminophenyl)-3-(4-methoxyphenyl)-prop-2-en-1-one (C4), (E)-1-(4-aminophenyl)-3-(4ethoxyphenyl)-prop-2-en-1-one (C9) chalcones through in silico approach. The molecular docking and the molecular electrostatic potential results indicated that the chalcones analyzed presented a strong interaction with the Leishmania major receptor, with affinity energy similar to the ligand co-crystallized. Besides, the interaction potential energy analysis from molecular dynamics simulations indicated the C9 ligand interacted more strongly than the 4-bromo-2,6-dichloro-N-(1,3,5-trimethyl-1H-pyrazolyl) benzenesulfonamide ligand with the Leishmania major receptor, especially for the Phe 88, Tyr 217 and His 219 residues. Therefore, the C9 chalcone might potentially treat Leishmaniasis disease.Communicated by Ramaswamy H. Sarma.


Assuntos
Chalconas , Leishmania , Leishmaniose , Humanos , Antiparasitários/uso terapêutico , Chalconas/farmacologia , Chalconas/química , Simulação de Acoplamento Molecular , Ligantes , Leishmaniose/tratamento farmacológico
18.
J Biomol Struct Dyn ; 41(15): 7463-7479, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36120936

RESUMO

Characterized as a neglected disease, Chagas disease is an infection that, in the current scenario, affects about 8 million people per year, with a higher incidence in underdeveloped countries, Chagas is responsible for physiological disabilities that result in impacts that are slightly reflected in world socioeconomic stability. Although treatments are based on drugs such as Benznidazole, the pathology lacks a continuous treatment method with low toxicological incidence. The present study estimates the anti-chagasic activity of the synthetic chalcone CPN2F based on the alignment between in vitro tests and structural classification in silico studies, molecular docking and ADMET studies. The in vitro tests showed a reduction in the protozoan metabolism in host cells (LLC-MK2). At the same time, the molecular docking models evaluate this growth inhibition through the synergistic effect associated with Benznida- zole against validated therapeutic target key stages (Cruzaine TcGAPDH and Trypanothione reductase) of the Trypanosoma cruzi development cycle. The in silico prediction results reveal an alignment between pharmacokinetic attributes, such as renal absorption and release, which allow the preparation of CPN2F as an antichagasic drug with a low incidence of organic toxicity.Communicated by Ramaswamy H. Sarma.

19.
J Biomol Struct Dyn ; 41(21): 12426-12444, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36644862

RESUMO

The prevalence of anxiety is a significant public health problem, being the 24th leading cause of disability in individuals affected by this disorder. In this context, chalcones, a flavonoid subclass obtained from natural or synthetic sources, interact with central nervous system (CNS) receptors at the same binding site as benzodiazepines, the primary drugs used in the treatment of anxiety. Thus, our study investigates the anxiolytic effect of synthetic chalcones derived from the natural product 2-hydroxy-3,4,6-trimethoxyacetophenone isolated from Croton anisodontus Müll.Arg. in modulating anxiolytic activity via GABAergic and serotoninergic neurotransmission in an adult zebrafish model. Chalcones 1 and 2 were non-toxic to adult zebrafish and showed anxiolytic activity via GABAA receptors. Chalcone 2 also had its anxiolytic action reversed by the antagonist granisetron, indicating the participation of serotonergic receptors 5HTR3A/3B in the anxiolytic effect. In addition, molecular docking results showed that chalcones have a higher affinity for the GABAA receptor than DZP and binding in the same region of the DZP binding site, indicating a similar effect to the drug. Furthermore, the interaction of chalcones with GABAA and 5-HT3A receptors demonstrates the anxiolytic effect potential of these molecules.Communicated by Ramaswamy H. Sarma.


Assuntos
Ansiolíticos , Chalconas , Animais , Adulto , Humanos , Ansiolíticos/farmacologia , Ansiolíticos/química , Ansiolíticos/uso terapêutico , Peixe-Zebra/metabolismo , Chalconas/farmacologia , Chalconas/química , Simulação de Acoplamento Molecular , Receptores de GABA-A/metabolismo , Ácido gama-Aminobutírico
20.
J Biomol Struct Dyn ; 41(21): 12055-12062, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36695084

RESUMO

Anxiety and epilepsy affect millions of people worldwide, and the treatment of these pathologies involves the use of Benzodiazepines, drugs that have serious adverse effects such as dependence and sedation, so the discovery of new anxiolytic and antiepileptic drugs are necessary. Many routes for synthesizing ibuprofen derivatives have been developed, and these derivatives have shown promising pharmacological effects. Therefore, this study aims to evaluate its anxiolytic and anticonvulsant effect against the adult Zebrafish animal model of Ibuprofen (IBUACT) and its interaction with the GABAergic receptor through in silico studies. The light/dark preference test (Scototaxis test) was used to evaluate the anxiolytic behavior of adult Zebrafish acutely treated with IBUACT and Diazepam, and their anticonvulsant effects were investigated through the pentylenetetrazol (PTZ)-induced seizure model. Animals treated with IBUACT showed anxiolytic behavior similar to Diazepam, and pretreatment with flumazenil reversed this behavior. PTZ-induced seizures were delayed by IBUACT in all three stages and were shown to bind strongly in the Diazepam region of GABAA. In addition, this work presents evidence of new pharmacological applications of ibuprofen derivative in pathologies of the central nervous system (CNS), opening the horizon for new studies.Communicated by Ramaswamy H. Sarma.


Assuntos
Ansiolíticos , Humanos , Animais , Ansiolíticos/efeitos adversos , Anticonvulsivantes/farmacologia , Peixe-Zebra , Ibuprofeno/farmacologia , Diazepam/efeitos adversos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
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