RESUMEN
A large number of infections are caused by multi-resistant bacteria worldwide, increasing to around 700,000 deaths per year. Because of that, many strategies are being developed to combat the resistance of microorganisms to drugs, and recently, chalcones have been studied for this purpose. Chalcones are known as α, ß-unsaturated ketones, characterized by having the presence of two aromatic rings that are joined by a three-carbon chain. They are a class of compounds considered an exceptional model due to chemical simplicity and a wide variety of biological activities, including anticancer, anti-inflammatory, antioxidants, antimicrobials, anti-tuberculosis, anti-HIV, antimalarial, anti-allergic, antifungal, antibacterial, and antileishmaniasis. The objective of this work was to evaluate the antibacterial and antibiotic modifying activity of chalcone (2E)-1-(4'-aminophenyl)-3-(4-methoxyphenyl)-prop-2-en-1-one against the bacteria Staphylococcus aureus carrying a NorA and MepA efflux pump. The results showed that chalcone showed no toxicity on macrophage cells and was able to synergistically modulate the action of Norfloxacin and Ethidium Bromide against the bacteria Staphylococcus aureus 1199B and K2068, respectively. Furthermore, the theoretical physicochemical and pharmacokinetic properties of chalcone showed that it did not present a severe risk of toxicity such as genetic mutation or cardiotoxicity, constituting an excellent pharmacological active ingredient.
Asunto(s)
Chalcona , Chalconas , Infecciones Estafilocócicas , Antibacterianos/química , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Chalcona/farmacología , Chalconas/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/metabolismoRESUMEN
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.
Asunto(s)
Chalcona , Chalconas , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Chalcona/farmacología , Chalconas/farmacología , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Staphylococcus aureus/metabolismoRESUMEN
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, ß-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.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Chalconas/farmacología , Proteínas de Transporte de Membrana/metabolismo , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacocinética , Proteínas Bacterianas/antagonistas & inhibidores , Chalconas/farmacocinética , Etidio/farmacología , Humanos , Absorción Intestinal , Pruebas de Sensibilidad Microbiana , Modelos Biológicos , Simulación del Acoplamiento Molecular , Norfloxacino/farmacología , Staphylococcus aureus/metabolismoRESUMEN
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.