RESUMO
Six new lignans with various type of linkage between two C6-C3 fragments (1a, 1b, 2a, 2b, 3, 4), two new meroterpenoids (5, 6) and 24 known compounds (7-30) were isolated from an EtOH extract of the stems and leaves of Piper puberulum. The absolute configurations of enantiomers 1a and 1b were determined by single-crystal X-ray diffraction analysis, 2a and 2b were determined by comparing their calculated and experimental ECD spectra. Biogenetically, all the new lignans may come from the polymerization of two molecules of hydroxychavicol (30). In the anti-neuroinflammation activity assay, the IC50 values of fifteen compounds were lower than those of the positive control minocycline, and compound 1a showed good activity, but its enantiomer 1b showed no activity. Compound 1a have notable anti-neuroinflammatory activity, and can significantly decrease mRNA levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) in a dose-dependent manner.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Lignanas/farmacologia , Óxido Nítrico/antagonistas & inibidores , Piper/química , Extratos Vegetais/farmacologia , Terpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Linhagem Celular , Cristalografia por Raios X , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Lignanas/química , Lignanas/isolamento & purificação , Camundongos , Modelos Moleculares , Estrutura Molecular , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
Three new tyramine-type alkamides (1-3), three new natural products (4-6), five new N-acylated/formylated aporphine alkamides with different ratios of rotational isomers (7-11), and 20 known alkamides (12-31) were isolated from an EtOH extract of the stems and leaves of Piper puberulum. The absolute configurations of compounds 7, 8, and 10 were determined by single-crystal X-ray diffraction analysis. In the biological activity assay, compounds 3, 5, and 10-23 displayed inhibitory effects against lipopolysaccharide-induced NO release in BV-2 microglial cells, exhibiting IC50 values of 0.93-45 µM.