RESUMO
In 1998, sildenafil was marketed as the first FDA-approved oral drug for the treatment of erectile dysfunction (ED). During the last two decades, the commercialization of other synthetic phosphodiesterase 5 (PDE5) inhibitors has been paralleled by the rise of remedies based on natural molecules from different chemical classes (flavonoids, polyphenols and alkaloids in general). In this work, a set of in silico tools were applied to study a panel of 30 natural compounds claimed to be effective against ED in the scientific literature or in folk medicine. First, pharmacokinetic properties were analysed to exclude the compounds lacking in specific drug-like features. Estimated binding energy for PDE5 and selectivity towards other PDE isoforms were then considered to highlight some promising molecules. Finally, a detailed structural investigation of the interaction pattern with PDE in comparison with sildenafil was conducted for the best performing compound of the set.
Assuntos
Inibidores da Fosfodiesterase 5/química , Inibidores da Fosfodiesterase 5/farmacologia , Sítios de Ligação , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Simulação por Computador , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/química , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Medicina Tradicional , Inibidores da Fosfodiesterase 5/farmacocinética , Inibidores da Fosfodiesterase 5/uso terapêutico , Citrato de Sildenafila/farmacologiaRESUMO
Several members of the Brassicaeae family are known to possess beneficial properties which positively impact human diet, thanks to the presence of antioxidants, bioactive polyphenols and amino acids. B. rapa, one of the most widespread and economically relevant species, represents an outstanding example. The aim of this study is to investigate, at the molecular level, the effect of plant aging on the concentration of some biologically relevant compounds in different parts of the plant. Using HPLC and NMR techniques, the quantification of polyphenolic species (caffeic acid, quercetin and rutin), succinic acid and alanine was performed in flowers and leaves of young and mature B. rapa plants.