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In this study, biocatalytic transesterification reaction using Novozyme 435 ® (N435) lipase was employed to enhance the hydrophobicity of esculin, aiming to improve its solubility for commercial applications and enhance its bioactivity and oral viability. The acylation reaction of esculin with vinyl acetate was conducted at 60 °C and 200 rpm for 24 h. After chromatographic and spectroscopic analysis, two products were identified: the first one was monoacylated at the 6'-OH position of the glucosyl moiety of esculin (T R : 10.3 min and m/z 382.93 [M + H] + ), and the second one was diacylated at the 6'-OH and 3'-OH positions (T R : 13.0 min and m/z 424.93 [M + H] + ). The latter was the major product, with a conversion rate of 53.550 ± 0.368%, while the monoacetylated one showed 8.715 ± 0.064%. Both products were isolated by high-speed counter-current chromatography (HSCCC) using a two-phase system HEMWat 1:9:1:9 and characterized by NMR. In this way, these results improve the practical application of esculin, through the obtention of esculin mono and diacetates by fast and efficient biocatalysis reaction.

Research into natural products has led to the discovery of new drugs. This work shows relevant data on the antibacterial activity of Ocotea notata leaves. Dichloromethane fraction (DF) from leaves of O. notata showed antibacterial activity at the concentration of 512 μg/mL against strains of Staphylococcus. The DF was fractionated to investigate bioactive compounds and yielded six subfractions (DF1-DF6). The DF3, DF5, and DF6 showed bacteriostatic activity, and DF4 showed bactericidal activity at the concentration of 2048 μg/mL and additive effect when combined with the antibiotic oxacillin. The flavonoids miquelianin (1), isoquercitrin (2), reynoutrin (3), guaijaverin (4), and afzelin (5) were isolated from the DF4 and characterized via NMR and HPLC-DAD-MS/MS analyses. Flavonoids 1-5, especially reynoutrin (3), seem to be responsible for the DF4 antibacterial activity. Reynoutrin showed activity against Staphylococcus epidermidis ATCC 12228 and S. aureus methicillin-resistant ATCC 33591. This is the first report regarding the reynoutrin antibacterial activity and the first description of the flavonoid guaijaverin for O. notata., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: In Chagas disease (CD), a neglected tropical disease caused by the parasite Trypanosoma cruzi, the development of mental disorders such as anxiety, depression, and memory loss may be underpinned by social, psychological, and biological stressors. Here, we investigated biological factors underlying behavioral changes in a preclinical model of CD., Methodology/principal Findings: In T. cruzi-infected C57BL/6 mice, a kinetic study (5 to 150 days postinfection, dpi) using standardized methods revealed a sequential onset of behavioral changes: reduced innate compulsive behavior, followed by anxiety and depressive-like behavior, ending with progressive memory impairments. Hence, T. cruzi-infected mice were treated (120 to 150 dpi) with 10 mg/Kg/day of the selective serotonin reuptake inhibitor fluoxetine (Fx), an antidepressant that favors neuroplasticity. Fx therapy reversed the innate compulsive behavior loss, anxiety, and depressive-like behavior while preventing or reversing memory deficits. Biochemical, histological, and parasitological analyses of the brain tissue showed increased levels of the neurotransmitters GABA/glutamate and lipid peroxidation products and decreased expression of brain-derived neurotrophic factor in the absence of neuroinflammation at 150 dpi. Fx therapy ameliorated the neurochemical changes and reduced parasite load in the brain tissue. Next, using the human U-87 MG astroglioma cell line, we found no direct effect of Fx on parasite load. Crucially, serotonin/5-HT (Ser/5-HT) promoted parasite uptake, an effect increased by prior stimulation with IFNγ and TNF but abrogated by Fx. Also, Fx blocked the cytokine-driven Ser/5-HT-promoted increase of nitric oxide and glutamate levels in infected cells., Conclusion/significance: We bring the first evidence of a sequential onset of behavioral changes in T. cruzi-infected mice. Fx therapy improves behavioral and biological changes and parasite control in the brain tissue. Moreover, in the central nervous system, cytokine-driven Ser/5-HT consumption may favor parasite persistence, disrupting neurotransmitter balance and promoting a neurotoxic environment likely contributing to behavioral and cognitive disorders., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Vilar-Pereira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Leishmaniasis, a group of neglected infectious diseases, encompasses a serious health concern, particularly with visceral leishmaniasis exhibiting potentially fatal outcomes. Nucleoside hydrolase (NH) has a fundamental role in the purine salvage pathway, crucial for Leishmania donovani survival, and presents a promising target for developing new drugs for visceral leishmaniasis treatment. In this study, LdNH was immobilized into fused silica capillaries, resulting in immobilized enzyme reactors (IMERs). The LdNH-IMER activity was monitored on-flow in a multidimensional liquid chromatography system, with the IMER in the first dimension. A C18 analytical column in the second dimension furnished the rapid separation of the substrate (inosine) and product (hypoxanthine), enabling direct enzyme activity monitoring through product quantification. LdNH-IMER exhibited high stability and was characterized by determining the Michaelis-Menten constant. A known inhibitor (1-(β-d-Ribofuranosyl)-4-quinolone derivative) was used as a model to validate the established method in inhibitor recognition. Screening of three additional derivatives of 1-(β-d-Ribofuranosyl)-4-quinolone led to the discovery of novel inhibitors, with compound 2a exhibiting superior inhibitory activity (K i  = 23.37 ± 3.64 µmol/L) compared to the employed model inhibitor. Docking and Molecular Dynamics studies provided crucial insights into inhibitor interactions at the enzyme active site, offering valuable information for developing new LdNH inhibitors. Therefore, this study presents a novel screening assay and contributes to the development of potent LdNH inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)