RESUMO
The ethanolic extract of the bulbs of Fritillaria imperialis was subjected to fractionation by solvent-solvent extraction. The nonpolar fraction showed inhibitory activity against prolyl endopeptidase (PEP) (EC.3.4.21.26), a large intracellular enzyme that preferentially hydrolyze proline-containing oligopeptidase at the carboxylic side of a prolyl residue. We have isolated a diterpenoid isopimara-7,15-dien-19-oic acid (1) from the nonpolar fraction of F. imperialis, and on methylation of compound 1, a methylester 2 was obtained which is a known compound previously isolated from Fritillaria thunbergii. The present article describes the isolation and structural elucidation of isopimara-7,15-dien-19-oic acid (1) by single-crystal X-ray diffraction techniques along with its prolyl endopeptidase inhibitory activity.
Assuntos
Diterpenos/farmacologia , Inibidores Enzimáticos/farmacologia , Fritillaria , Fitoterapia , Extratos Vegetais/farmacologia , Serina Endopeptidases/efeitos dos fármacos , Diterpenos/administração & dosagem , Diterpenos/química , Diterpenos/uso terapêutico , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Humanos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Prolil Oligopeptidases , Difração de Raios XRESUMO
Compounds isolated from the hexane extract of the leaves of Syzygium samarangense (Blume) Merr. & L. M. Perry were tested for inhibitory activity against the following serine proteases: trypsin, thrombin and prolyl endopeptidase. The compounds were identified as an intractable mixture of alpha-carotene and beta-carotene (1), lupeol (2), betulin (3), epi-betulinic acid (4), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (5), 2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone (6), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (7), 2',4'-dihydroxy-6'-methoxy-3'-methyldihydrochalcone (8) and 7-hydroxy-5-methoxy-6,8-dimethylflavanone (9). Hydrogenation of compounds 5, 6 and 7 yielded compound 8, 2'-hydroxy-4',6'-dimethoxy-3'-methyldihydrochalcone (10) and 2',4'-dihydroxy-6'-methoxy-3',5'-dimethyldihydrochalcone (11), respectively. The hydrogenated products of compounds 6 and 7 were also tested for enzyme inhibitory activity. In addition, beta-sitosterol (12) and beta-D-sitosterylglucoside (13) were also isolated. This is the first report of the isolation of compounds 1-6, 8 and 13 from this plant. Compounds 3-8 and 10 exhibited significant and selective inhibition against prolyl endopeptidase among three serine proteases. This is the first report of this kind of activity for all these compounds.
Assuntos
Extratos Vegetais/isolamento & purificação , Inibidores de Proteases/isolamento & purificação , Syzygium/química , Hexanos , Cinética , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Extratos Vegetais/química , Folhas de Planta/química , Prolil Oligopeptidases , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Serina Endopeptidases/metabolismo , Trombina/metabolismo , Tripsina/metabolismoRESUMO
Fermentation of (+)-androst-4-ene-3,17-dione (1) with Curvularia lunata for 10 days yielded five oxidative and reductive metabolites, androsta-1,4-diene-3,17-dione (2), 17beta-hydroxyandrosta-1,4-dien-3-one (3), 11alpha-hydroxyandrost-4-ene-3,17-dione (4), 11alpha,17beta-dihydroxyandrost-4-en-3-one (5) and 15alpha-hydroxyandrosta-1,4-dien-17-one (6). The structures of these metabolites were elucidated on the basis of spectroscopic techniques. These microbially transformed products were assayed against the clinically important enzymes, tyrosinase and prolyl endopeptidase.
Assuntos
Androstenodiona/farmacocinética , Ascomicetos/metabolismo , Fitoterapia , Androstenodiona/administração & dosagem , Androstenodiona/química , Animais , Biotransformação , Fermentação , Humanos , Espectroscopia de Ressonância Magnética , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacocinéticaRESUMO
Incubation of cortisol (1) with Gibberella fujikuruoi for 12 days yielded an oxidatively cleaved product, 11beta-hydroxyandrost-4-en-3,17-dione (2), while incubation with Bacillus subtilis and Rhizopus stolonifer yielded the reduced product, 11beta, 17alpha,20,21-tetrahydroxy-(20S)-pregn-4-en-3-one (3). Other reduced products, 11beta, 17alpha, 21-trihydroxy-5alpha-pregnan-3, 20-dione (4) and 3beta, 11beta, 17alpha, 21-tetrahydroxy-5alpha-pregnan-20-one (5) were obtained by incubation of compound 1 with Bacillus cerus. The inhibitory activity of compounds 1-5 against prolyl endopeptidase enzyme (PEP) was also assayed. Compounds 2 (IC50 162.8 microM) and 4 (IC50 157 microM) have shown significant inhibitory activity against PEP.
Assuntos
Gibberella/enzimologia , Hidrocortisona/metabolismo , Hidrocortisona/farmacologia , Serina Endopeptidases/farmacologia , Biotransformação , Indústria Farmacêutica , Inibidores Enzimáticos/farmacologia , Extratos Vegetais/farmacologia , Prolil OligopeptidasesRESUMO
The inhibitory effects of seven diterpenes, belonging to three different structural classes and isolated from the bark of Xylopia aethiopica, were investigated against the enzymes prolyl endopeptidase (PEP) and alpha-thrombin. Five compounds exhibited inhibitory activity against them.
Assuntos
Annonaceae/enzimologia , Anticoagulantes/uso terapêutico , Diterpenos/uso terapêutico , Fitoterapia , Serina Endopeptidases/uso terapêutico , Trombina/antagonistas & inibidores , Animais , Anticoagulantes/química , Diterpenos/química , Diterpenos/classificação , Avaliação Pré-Clínica de Medicamentos , Concentração Inibidora 50 , Casca de Planta/química , Prolil OligopeptidasesRESUMO
Phytochemical investigation of the stem bark extract of Boswellia papyrifera afforded two new stilbene glycosides, trans-4',5-dihydroxy-3-methoxystilbene-5-O-{alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranoside (1), trans-4',5-dihydroxy-3-methoxystilbene-5-O-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranoside (2), and a new triterpene, 3alpha-acetoxy-27-hydroxylup-20(29)-en-24-oic acid (3), along with five known compounds, 11-keto-beta-boswellic acid (4), beta-elemonic acid (7), 3alpha-acetoxy-11-keto-beta-boswellic acid (8), beta-boswellic acid (9), and beta-sitosterol (10). The stilbene glycosides exhibited significant inhibition of phosphodiesterase I and xanthine oxidase. The triterpenes (3-9) exhibited prolyl endopeptidase inhibitory activities.
Assuntos
Boswellia/química , Glicosídeos/isolamento & purificação , Plantas Medicinais/química , Estilbenos/isolamento & purificação , Triterpenos/isolamento & purificação , Camarões , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Concentração Inibidora 50 , Estrutura Molecular , Estilbenos/química , Estilbenos/farmacologia , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Isoprenylated flavonoids 5,7-dihydroxy-3'-(2-hydroxy-3-methyl-3-butenyl)-3,6,4'-trimethoxyflavone (1), 3,7-dihydroxy-3'-(2-hydroxy-3-methyl-3-butenyl)-5,6,4'-trimethoxyflavone (2) and an isoprenylated acetophenone derivative (3) have been isolated from Duranta repens along with known compounds, 5-hydroxy-3,6,7,4'-tetramethoxyflavone (4), rosenonolactone (5), 6,7-dimethoxycoumarin (6), 5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (7) and 5alpha,8alpha-epidioxyergosta-6,9(11),22-trien-3beta-ol (8), isolated for the first time from this species. Their structures and the relative configuration were determined by spectroscopic methods (1H- and 13C-NMR, IR, UV and MS) and two-dimensional (2D)-NMR experiments. The compounds 1-5 showed inhibitory activity against prolyl endopeptidase while 4 and 5 were also active against thrombin.
Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Serina Endopeptidases/metabolismo , Trombina/antagonistas & inibidores , Verbenaceae/química , Animais , Bovinos , Espectroscopia de Ressonância Magnética , Extratos Vegetais/química , Plantas Medicinais/química , Prolil Oligopeptidases , Inibidores de Serina Proteinase/química , Inibidores de Serina Proteinase/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
A novel sesterterpene, leucosceptrine, was isolated from the medicinal plant Leucosceptrum canum from Nepal. The structure was determined by single-crystal X-ray diffraction and spectroscopic techniques. The biosynthesis of leucosceptrine (1) is proposed here. Leucosceptrine (1) exhibited prolylendopeptidase inhibitory activity.
Assuntos
Lamiaceae/química , Serina Endopeptidases/metabolismo , Inibidores de Serina Proteinase/isolamento & purificação , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Nepal , Plantas Medicinais/química , Prolil Oligopeptidases , Inibidores de Serina Proteinase/química , Inibidores de Serina Proteinase/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
A new pentacyclic triterpenoid, 3alpha-(3",4"-dihydroxy- trans-cinnamoyloxy)- D-friedoolean-14-en-28-oic acid ( 1) has been isolated along with two known compounds, rhamnocitrin ( 2) and isorhamnetin ( 3) from the aerial parts of Tamarix hispida Willd. Compound 1 was found to be a potent antioxidant. In addition, compounds 1 - 3 showed significant inhibitory activity against prolylendopeptidase (PEP).
Assuntos
Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Fitoterapia , Serina Endopeptidases/efeitos dos fármacos , Tamaricaceae , Triterpenos/farmacologia , Antioxidantes/química , Compostos de Bifenilo , Inibidores Enzimáticos/química , Humanos , Concentração Inibidora 50 , Picratos/química , Componentes Aéreos da Planta , Prolil Oligopeptidases , Triterpenos/químicaRESUMO
A reinvestigation with a modified extraction procedure of Euphorbia decipiens resulted in the isolation and structure elucidation of three new myrsinane-type diterpene esters (1-3). The structures of compounds 1-3 were elucidated by spectroscopic data interpretation. Compound 1 showed inhibitory activity against prolyl endopeptidase (PEP), whereas compound 2 exhibited DNA-damaging activity in a mutant yeast bioassay.
Assuntos
Diterpenos/isolamento & purificação , Euphorbia/química , Plantas Medicinais/química , Inibidores de Serina Proteinase/isolamento & purificação , Chryseobacterium/enzimologia , Dano ao DNA , Diterpenos/química , Diterpenos/farmacologia , Irã (Geográfico) , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Prolil Oligopeptidases , Saccharomyces cerevisiae/efeitos dos fármacos , Serina Endopeptidases/efeitos dos fármacos , Serina Endopeptidases/metabolismo , Inibidores de Serina Proteinase/química , Inibidores de Serina Proteinase/farmacologiaRESUMO
Three new diterpene esters with a myrsinol-type skeleton have been isolated from Euphorbia decipiens BOISS. & BUHSE. The structure elucidation of the isolated compounds was based primarily on two-dimensional (2D)-NMR techniques including correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond correlation (HMBC) and nuclear Overhauser effect spectroscopy (NOESY) experiments. Compounds 1 and 3 are active against prolyl endopeptidase and compound 2 showed inhibitory activity against urease enzyme.