RESUMO
Three new C19-norditerpenoid alkaloids (1â»3), along with two known C19-norditerpenoid alkaloids (4,5), have been isolated from Aconitum szechenyianum. Based on extensive spectroscopic techniques (1D, 2D-NMR, IR, and MS) and chemical methods, their structures were established as szechenyianine D (1), szechenyianine E (2), szechenyianine F (3), 8-O-methyl-14-benzoylaconine (4), and spicatine A (5). The immunosuppressive effects of compounds 1â»5 were studied using a ConA-induced or LPS-induced splenocyte proliferation model. In vitro tests showed that Compounds 2, 4, and 5 suppressed ConA-induced or LPS-induced splenocyte proliferation in a concentration-dependent manner. The CC50/IC50 values of 2, 4, and 5 suggested that these compounds were potential immunosuppressive agents for the treatment of autoimmune diseases characterized by arthritis, such as rheumatoid arthritis.
Assuntos
Aconitum/química , Artrite Reumatoide/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Diterpenos/química , Aconitina/análogos & derivados , Aconitina/química , Aconitina/isolamento & purificação , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/patologia , Concanavalina A/toxicidade , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Humanos , Imunossupressores/química , Imunossupressores/isolamento & purificação , Imunossupressores/farmacologia , Lipopolissacarídeos/toxicidade , Estrutura Molecular , Raízes de Plantas/química , Baço/efeitos dos fármacos , Baço/lesões , Baço/patologiaRESUMO
Three new C19-norditerpenoid alkaloids (1-3), along with two known C19-norditerpenoid alkaloids (4-5) have been isolated from Aconitum szechenyianum. Their structures were established by extensive spectroscopic techniques and chemical methods as szechenyianine A (1), szechenyianine B (2), szechenyianine C (3), N-deethyl-3-acetylaconitine (4), and N-deethyldeoxyaconitine (5). Additionally, compounds 1-5 were tested for the inhibition of NO production on LPS-activated RAW264.7 cells with IC50 values of 36.62 ± 6.86, 3.30 ± 0.11, 7.46 ± 0.89, 8.09 ± 1.31, and 11.73 ± 1.94 µM, respectively, while the positive control drug dexamethasone showed inhibitory activity with IC50 value of 8.32 ± 1.45 µM. The structure-activity relationship of aconitine alkaloids were discussed.