The use of the bacterial efflux pump mechanism to reduce the concentrations of antibiotics in the intracellular to the extracellular region is one of the main mechanisms by which bacteria acquire resistance to antibiotics. The present study aims to evaluate the antibacterial activity of the α,β-amyrin mixture isolated from Protium heptaphyllum against the multidrug-resistant strains of Escherichia coli 06 and Staphylococcus aureus 10, and to verify the inhibition of the efflux resistance mechanisms against the strains of S. aureus 1199B and K2068, carrying the NorA and MepA efflux pumps, respectively. The α,β-amyrin did not show clinically relevant direct bacterial activity. However, the α,β-amyrin when associated with the gentamicin antibiotic presented synergistic effect against the multidrug-resistant bacterial strain of S. aureus 10. In strains with efflux pumps, α,β-amyrin was able to inhibit the action of the efflux protein NorA against Ethidium Bromide. However, this inhibitory effect was not observed in the MepA efflux pump. In addition, when evaluating the effect of standard efflux pump inhibitors, clorptomazine and CCCP, α,β-amyrin showed a decrease in MIC, demonstrating the presence of the efflux mechanism through synergism. Docking studies indicate that α, β-amyrin have a higher affinity energy to MepA, and NorA than ciprofloxacin and norfloxacin. Also, α, β-amyrin bind to the same region of the binding site as these antibiotics. It was concluded that the α, β-amyrin has the potential to increase antibacterial activity with the association of antibiotics, together with the ability to be a strong candidate for an efflux pump inhibitor. Communicated by Ramaswamy H. Sarma

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 GABA_A receptors. Chalcone 2 also had its anxiolytic action reversed by the antagonist granisetron, indicating the participation of serotonergic receptors 5HTR_3A/3B in the anxiolytic effect. In addition, molecular docking results showed that chalcones have a higher affinity for the GABA_A 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 GABA_A and 5-HT_3A receptors demonstrates the anxiolytic effect potential of these molecules. Communicated by Ramaswamy H. Sarma

Background: Studies on natural or synthetic products from chalcones have shown to be very promising due to their peculiar structure that allows different possibilities of reallocation that will define their diverse bioactivities in the creation of new substances. This creation is facilitated by the synthesis of substances in conjunction with the molecular study, which allows a considerable advancement in research, reducing the number of in vitro tests. Objective: This work focuses on the antibacterial activity of chalcones against Staphylococcus aureus, which causes several diseases and is one of the main microorganisms with increasing resistance to conventional drugs. Methods: Articles that studied antibacterial activity, efflux pump, or molecular docking were considered complimentary analyses of chalcones. From these data, molecular docking and ADMET of the first five chalcones were performed with the best activity found. Results: The result of the antimicrobial activity against Staphylococcus aureus was confirmed through in silico study and pharmacokinetic data. Conclusion: The results of the antimicrobial activity of the most active chalcones against Staphylococcus aureus were supported by in silico and pharmacokinetic studies, which not only confirmed their potential to act against resistant strains but also established the future utility of chalcones as lead molecules or prototypes for the synthesis of potent new antimicrobial agents against Staphylococcus aureus.