RESUMO
A novel labdane type diterpenoid, 15-nor-8-labden-13-ol, named kujigamberol C, was isolated from Kuji amber using a modified isolation method to increase the yield of biologically active compounds. The structure was determined using HREIMS, 1D and 2D NMR. Kujigamberol C showed growth-restoring activity against mutant yeast via Ca2+-signal transduction.
Assuntos
Âmbar/química , Sinalização do Cálcio/efeitos dos fármacos , Diterpenos/farmacologia , Animais , Linhagem Celular , Diterpenos/isolamento & purificação , Espectroscopia de Ressonância Magnética/métodos , Ratos , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
A podocarpatriene and a labdatriene derivative, named kujiol A [13-methyl-8,11,13-podocarpatrien-19-ol (1)] and kujigamberol B [15,20-dinor-5,7,9-labdatrien-13-ol (2)], respectively, were isolated from Kuji amber through detection with the aid of their growth-restoring activity against a mutant yeast strain ( zds1Δ erg3Δ pdr1Δ pdr3Δ), which is known to be hypersensitive with respect to Ca2+-signal transduction. The structures were elucidated by spectroscopic data analysis. Compounds 1 and 2 are rare organic compounds from Late Cretaceous amber, and the mutant yeast used seems useful for elucidating a variety of new compounds from Kuji amber specimens, produced before the K-Pg boundary.
Assuntos
Âmbar/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Âmbar/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
A new norlabdane compound, named kujigamberol has previously been isolated from Kuji amber (but not from Baltic amber) by activity guided fractionation. However, there has been no study of biological compounds in Dominican amber. Biological activities were examined using the hypersensitive mutant yeast (zds1Δ erg3Δ pdr1Δ pdr3Δ) with respect to Ca(2+)-signal transduction, enzymes and rat basophilic leukemia (RBL)-2H3 cells. The structures were elucidated on the basis of spectral analysis including high resolution (HR)-EI-MS, 1D NMR and 2D NMR. Three diterpenoid compounds, 5(10)-halimen-15-oic acid (1), 3-cleroden-15-oic acid (2) and 8-labden-15-oic acid (3), which are different from the bioactive compounds in Kuji and Baltic ambers, were isolated from Dominican amber. They inhibited both calcineurin (CN) (IC50=40.0, 21.2 and 34.2µM) and glycogen synthase kinase-3ß (GSK-3ß) (IC50=48.9, 43.8 and 41.1µM) which are involved in the growth restored activity against the mutant yeast. The most abundant compound 2 showed inhibitory activity against both degranulation and Ca(2+)-influx in RBL-2H3 cells. The compounds having the growth restoring activity against the mutant yeast have potential as anti-allergic compounds.
Assuntos
Âmbar/química , Sinalização do Cálcio/efeitos dos fármacos , Degranulação Celular/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Animais , Linhagem Celular , República Dominicana , RatosRESUMO
A new compound, 15,20-dinor-5,7,9-labdatriene-18-ol (1), named kujigamberol, was isolated from amber, fossilized tree resin from the Kuji area in Japan, has been dated as being 85 million years old (late Cretaceous). Kujigamberol was identified using the hypersensitive mutant yeast (zds1∆ erg3∆ pdr1∆ pdr3∆) with respect to Ca(2+)-signal transduction. The structure was elucidated on the basis of spectroscopic analysis including 1D NMR, 2D NMR and HR-EI-MS. It was different from known diterpenoids with a similar activity isolated from Baltic amber (agathic acid 15-monomethyl ester (2), dehydroabietic acid (3) and pimaric acid (4)). Kujigamberol showed glycogen synthase kinase-3ß (GSK-3ß) inhibition activity involving the growth restored activity against the mutant yeast and was cytotoxic to HL60 cells (IC(50)=19.6 µM).
