Navegando por Palavras-chave "Lauraceae"

Agora exibindo 1 - 2 de 2
  • Imagem de Miniatura
    Item
    Acesso aberto (Open Access)
    Absolute configuration reassignment of nectamazin A: Implications to related neolignans
    (Elsevier, 2023-08-21) Batista, Andrea Nastri de Luca; Santos, Carlos Henrique Totini dos; Albuquerque, Ana Carolina Ferreira de; Santos Jr, Fernando Martins dos; Garcez, Fernanda Rodrigues; Batista Jr, João Marcos [UNIFESP]; http://lattes.cnpq.br/4209224090500050
    The ability of nature to produce structurally complex molecules makes the determination of the absolute configu- ration of natural products a challenging task. Although extensive NMR analysis generally allows for the reliable assignment of relative configurations, the assignments of absolute stereochemistry are commonly performed by empirical comparisons of optical rotation (OR) and/or electronic circular dichroism (ECD) data obtained for related molecules. Such an approach, however, may lead to misassignments and consequent error propagations. Herein, we present the case of the bicyclo(3.2.1)octane neolignan named (+)-nectamazin A. This compound was first reported in 2009 from Nectandra amazonum Nees. (Lauraceae) and had its absolute configuration determined as 7R,8S,3′S,4′R,5′S by means of experimental ECD spectroscopy. Our chemical studies on Ocotea aciphylla (Lauraceae) led to the isolation of (+)-nectamazin A. The extensive analysis of OR, ECD, and vibrational CD data aided by quantum chemical cal- culations, however, indicated (+)-nectamazin A to have the 7S,8R,3′R,4′S,5′R absolute configuration, in conflict with the configuration reported in the literature. The cause of the original incorrect assignment of (+)-nectamazin A derives from the direct comparison of experimental OR and ECD data obtained for structurally related molecules with different chromophoric systems. As an alternative, VCD spectroscopy is presented as a more reliable and sensitive technique to stereochemical investigations of bicyclo(3.2.1)octane neolignans.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Avaliação do efeito do Deidrodieugenol extraído das folhas de Nectandra leucantha (Lauraceae) em modelo experimental de asma grave
    (Universidade Federal de São Paulo (UNIFESP), 2020-04-17) Ponci, Vitor [UNIFESP]; Lago, João Henrique Ghilardi [UNIFESP]; Universidade Federal de São Paulo
    Asthma is a chronic disease with high global prevalence, affecting around 235 million people around the globe. In Brazil, a 10% prevalence is estimated, with approximately 2.500 deaths per year, according to DATASUS national database. Asthma control is based on corticosteroid therapy, however portions of asthmatic patients do not respond well to this treatment, originating the difficult-to-control severe asthma phenotype. These patients have elevated airway hyperresponsiveness, higher frequency of exacerbations and remodeling and are responsible for a significant portion of total healthcare costs with asthma due to hospitalizations, specially the mixed-granulocytic endotype. For this endotype of asthma, there is a significant contribution of neutrophils, besides the elevated concentration of eosinophils as well and no specific therapy available. The aim of this study was to isolate, from the leaves of Nectandra leucantha, the neolignoid dehydrodieugenol, which structure was defined through nuclear magnetic resonance and mass spectra analysis, allied with the validation of a synthetic approach for the acquisition of dehydrodieugenol from eugenol as starting material to evaluate its antiasthmatic potential in a mice model of mixed-granulocytic asthma. Dehydrodieugenol was administered intraperitoneally in three different regimen doses (10 mg/kg for 8 days, 10 mg/kg for 4 days and 20 mg/kg for 4 days) in ovalbumin-sensitized BALB/C male mice in order to find the most efficacious dose regimen to further evaluate its potential regarding improvement in lung function and inflammatory parameters in comparison to positive control dexamethasone (5 mg.kg-1, i.p.). Based on dose-response analysis, dehydrodieugenol (20 mg.kg–1) for 4 days of treatment was the only dose regimen that resulted in significant reduction on both eosinophils (ΔBISxOVA=6,09.104/mL; P<0,05) and neutrophils (ΔBISxOVA=2,40.104/mL; P<0,001) on bronchoalveolar lavage fluid in ovalbuminsensitized mice with no statistically difference from dexamethasone (P>0,05). As for lung function parameters, dehydrodieugenol (20 mg.kg–1) significantly reduced airway (ΔRawBISxOVA = 1,67 cmH2O.s/mL, P<0,05) and tissue (ΔGtis BISxOVA = 4,60 cmH2O.s/mL; P<0,05) resistance in comparison to ovalbumin group, with similar efficacy to positive control dexamethasone. Airway hyperresponsiveness to intravenous methacholine was reduced with dehydrodieugenol but was inferior to dexamethasone in higher doses. No changes were observed on elastance in any group. Dehydrodieugenol showed good overall safety profile, without any deaths or concerns observed during the protocol and no change in liver, thymus or spleen mass compared to saline control group. Moreover, its production has low costs and few steps, making it possible to produce in larger scales. Thus, dehydrodieugenol (20 mg.kg–1) showed great antiasthmatic potential for the treatment of mixed-granulocytic asthma, for the substitution or combination therapy with corticosteroids, in order to reduce the risk of adverse events related to its chronic use, and can be obtained in few steps through the chemical preparation from eugenol.