RESUMEN
The combination of computational methods and experimental data from Nuclear Magnetic Resonance (NMR) is a considerably valuable tool in the elucidation of new natural product structures and, also, in the structural revision of previously reported compounds. Until recently, only classical statistical parameters were used, for example, linear correlation coefficient (R2 ), mean absolute error (MAE), or root mean square deviation (RMSD), as a way to statistically "validate" the structure pointed out by experimental NMR spectra. Regarding the resolution of the relative configuration of organic molecules, novel tools were available in the last few years to assist in the NMR elucidation process. The most relevant are DP4+, which is based on a Bayesian probability, and ANN-PRA, which is based on artificial neural networks. The combined application of these tools has become the most accurate and important alternative to solve structural and stereochemical problems in natural product chemistry. Therefore, herein, in this case study, we intended to promote these novel tools, exploring the strengths and limitations of each approach in resolving the relative configuration of the sesquiterpene alpha-bisabol. We also highlighted the advantages of the complementary use of H- and C-DP4+ to obtain optimal results in the differentiation of the stereoisomers, validating the proposal with ANN-PRA method.
Asunto(s)
Productos Biológicos , Teorema de Bayes , Productos Biológicos/química , Espectroscopía de Resonancia Magnética/métodos , EstereoisomerismoRESUMEN
Praziquantel is the drug of choice for the treatment of schistosomiasis. However, several strains of Schistosoma mansoni are resistant to praziquantel, making it necessary to discover new drugs that might be used for its treatment. With this in mind, the properties of a schistosomicidal ethanolic extract of Garcinia brasiliensis Mart. epicarp, the fractions obtained by partitioning this extract, including the hexane fractions, ethyl acetate fraction, and the aqueous fraction, and the isolated compounds 7-epiclusianone, a major component from these fractions, and fukugetin were tested in vitro on adult worms of S. mansoni. Mortality, damage to membranes, and excretory system activity were observed at 100.0, 50.0, 75.0, and 14.0 µg/mL for the ethanolic extract of G. brasiliensis Mart. epicarp, its hexane fractions, the ethyl acetate fraction, and 7-epiclusianone, respectively. For 7-epiclusianone, these data were confirmed by fluorescent probe Hoechst 33â258 and resorufin. Additionally, the biocidal effect of 7-epiclusianone was even higher than the hexane fractions. Moreover, an inhibitory effect of 7-epiclusianone on the egg laying of female adult S. mansoni worms was observed in cercariae and schistossomula. Thus, 7-epiclusianone is a promising schistosomicidal compound; however, more studies are needed to elucidate its mechanism of toxicity and to evaluate the in vivo activity of this compound.
Asunto(s)
Benzofenonas/farmacología , Benzoquinonas/farmacología , Garcinia/química , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis/tratamiento farmacológico , Esquistosomicidas/farmacología , Animales , Benzofenonas/química , Benzofenonas/aislamiento & purificación , Benzoquinonas/química , Benzoquinonas/aislamiento & purificación , Biflavonoides/farmacología , Femenino , Masculino , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Esquistosomicidas/química , Esquistosomicidas/aislamiento & purificaciónRESUMEN
The damaging effects of sunlight to the skin has triggered studies that involve the synthesis and extraction of organic compounds from natural sources that can absorb UV radiation, and studies on polyphenolic compounds with antioxidant and anti-inflammatory properties that can be used as photochemopreventive agents for reducing skin damage. We investigated the in vitro and in vivo photoprotective/photochemopreventive potential of Garcinia brasiliensis epicarp extract (GbEE). We evaluated the cell viability of L929 fibroblasts after UVB exposure using a quartz plate containing the extract solution or the GbEE formulation. The in vivo photoprotective effect of the GbEE formulation was evaluated by measuring the UVB damage-induced decrease in endogenous reduced glutathione (GSH), the increase in myeloperoxidase (MPO) activity and secretion of cytokines IL-1ß and TNF-α. The in vitro methodology using fibroblasts showed that the photoprotective properties of the GbEE solutions and 10% GbEE formulation were similar to the commercial sunscreen (SPF-15). In vivo results demonstrated of the GbEE formulation in decreasing UVB induced-damage such as GSH depletion, an increased in MPO activity and secretion of cytokines IL-1ß and TNF-α. The results showed that the extract has great potential for use as a sunscreen in topical formulations in addition to UV filters.