ABSTRACT
Isolated substances and those organically synthesized have stood out over the years for their therapeutic properties, including their antibacterial activity. These compounds may be an alternative to the production of new antibiotics or may have the ability to potentiate the action of preexisting ones. In this context, the objective of this study was to evaluate the in vitro antibacterial and efflux pump inhibitory activity of hydroxyamines derived from lapachol and norlachol, more specifically the compounds 2-(2-Hydroxyethylamino)-3-(3-methyl-2-butenyl)-1,4 dihydro-1,4-naphthalenedione, 2-(2-Hydroxyethylamino)-3-(2-methyl-propenyl)[1,4]naphthoquinone and 2-(3-Hydroxypropylamino)-3-(3-methyl-2-butenyl)-[1,4]naphthoquinone, against Staphylococcus aureus strains carrying the NorA efflux pump mechanism. The substances were synthesized from 2-hydroxy-quinones, lapachol and nor-lapachol, obtaining the corresponding 2-methoxylated derivatives via dimethyl sulfate alkylation in a basic medium, which then reacted chemoselectively with 2-ethanolamine and 3-propanolamine to form the corresponding amino alcohols. All three molecules underwent a virtual structure-based analysis (docking). The antibacterial activity of the substances was measured by determining their Minimum Inhibitory Concentration (MIC) and a microdilution assay was performed to verify efflux pump inhibition using the substances at a sub-inhibitory concentration. The results were subjected to statistical analysis using an analysis of variance (ANOVA) followed by Bonferroni's post hoc test. The substances obtained MIC values ≥1024 µg/mL, however, a significant reduction of their MICs was observed when the substances were associated with norfloxacin and ethidium bromide, with this effect being attributed to efflux pump inhibition. Following a virtual analysis based on its structure (docking), information regarding the affinity of new ligands for the ABC efflux pump were observed, thus contributing to the understanding of their mechanism of molecular interactions and the discovery of functional ligands associated with a reduction in bacterial resistance.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Multidrug Resistance-Associated Proteins/antagonists & inhibitors , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemical synthesis , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Computer Simulation , Drug Evaluation, Preclinical , Microbial Sensitivity Tests , Molecular Docking Simulation , Multidrug Resistance-Associated Proteins/chemistry , Multidrug Resistance-Associated Proteins/genetics , Naphthoquinones/chemistry , Norfloxacin/chemistry , Norfloxacin/pharmacology , Staphylococcus aureus/geneticsABSTRACT
A Aguardente Alemã (AA), produzida a partir dos extratos das raízes de Operculina macrocarpa e Convolvulus scammonia, conhecida, também, como jalapa composta, é indicadacomo laxante, mas é utilizada, popularmente, para as mais variadas patologias. Este trabalho objetivou delinear o perfi l do usuário desse fi toterápico, a forma de administração e as principais indicações de uso relatadas pelo usuário, utilizando, para isto, um questionário aplicado à população (n = 125) no momento da dispensação do produto em farmácias de Fortaleza, Ceará. Os usuários eram, na sua maioria, mulheres, com idade de 41 a 60 anos. A administração de AA era feita, em geral, com uma colher de chá (5 mL; 46,4%), uma vez por dia (87%), sem um horário fi xo de tomada; administrando com chá ou água, prioritariamente. A população referiuusar AA, principalmente, para problemas circulatórios (63%) e cefaléia (13,1%). A atividade purgativa, rotulada na formulação do produto comercializado, foi pouco referida. Desta feita, nossos resultados subsidiam importantes informações para o processo de certifi cação de AA junto às agências regulatórias e enfatizam a necessidade de mais estudos de vigilância póscomercialização, para a garantia do uso racional do produto pelo usuário.
The Aguardente Alemã (AA), produced from extracts of the roots of Operculina macrocarpa and Convolvulus scammonea, also known as composed jalapa, is indicated as laxative, but it is used, popularly, for several diseases. Our objective was to delineate the user profi le of this herbal medicine, the way it is managed and the main use indications referred by users through a questionnaire applied to the population(n = 125) at the moment of the AA dispensing in community pharmacies of Fortaleza, Ceará. The users were mainly women, aged between 41 and 60 years. The administration of AA was generally done with a tea spoon (5 mL; 46.4%), once per day (87%), without an established time for taking; managing it with tea and water, principally. It was indicated by the population for using in diseases as circulatory problems (63%) and migraine (13.1%). The laxative activity, labeled in the formulation of the product, was poorly related. Thus, our results provide important information for the certifi cation process of AA to the regulatory agencies and emphasize thenecessity of more studies of post-marketing surveillance for the guarantee of the rational use of this product to the user.