RESUMO
The new methylated grindelane diterpenoid, 7ß-hydroxy-8(17)-dehydrogrindelic acid (1b), together with the known 7α-hydroxy-8(17)-dehydrogrindelic acid (2a), 6-oxogrindelic acid (3a), 4ß-hydroxy-6-oxo-19-norgrindelic (4a), 19-hydroxygrindelic acid (5a), 18-hydroxygrindelic acid (6a), 4α-carboxygrindelic acid (7a), 17-hydroxygrindelic acid (8a), 6α-hydroxygrindelic acid (9a), 8,17-bisnor-8-oxagrindelic acid (10a), 7α,8α-epoxygrindelic acid (11a), and strictanonic acid (12a) as methyl esters were obtained from an Argentine collection of Grindelia chiloensis (Cornel.) Cabrera. Their structures and relative configurations were established on the basis of spectroscopic analysis. CHCl3 extract from the aerial parts and their pure compounds were evaluated for their antifungal and depigmenting effects. Methyl ester derivative of 10a (10b) exhibited a remarkable mycelial growth inhibition against Botritis cinerea with an IC50 of 13.5 µg ml-1 . While the new grindelane 1b exerted a clear color reduction of the yellow-orange pigment developed by Fusarium oxysporum against UV-induced damage.
Assuntos
Antifúngicos/isolamento & purificação , Grindelia/química , Preparações Clareadoras de Pele/isolamento & purificação , Antifúngicos/farmacologia , Diterpenos , Fusarium/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Preparações Clareadoras de Pele/farmacologiaRESUMO
Seven new withanolides, salpichrolides O-U (1-7), the known 2,3-dihydrosalpichrolide B (9), a substance not previously isolated from a natural source, and three known compounds, salpichrolide D (8), salpichrolide A (10), and salpichrolide C (11), were isolated and characterized from the aerial parts of Salpichroa origanifolia and S. tristis var. lehmannii. Compounds 1-4 and 8 have an oxygenated D ring, while compounds 5-7 and 9-11 possess a six-membered aromatic D ring. The structures of the isolated compounds were identified by analysis of their spectroscopic data including NMR and MS. Withanolides 1, 3, 8, 10, and 11 exhibited selective radicle growth inhibition toward Lactuca sativa (lettuce) at 150 and 400 ppm.
Assuntos
Solanaceae/química , Vitanolídeos/isolamento & purificação , Vitanolídeos/farmacologia , Argentina , Ergosterol/análogos & derivados , Estrutura Molecular , Vitanolídeos/químicaRESUMO
A series of 5-hydroxy-1,4-naphthoquinones analogues was synthesized from juglone (6) and their antiproliferative activity against a representative panel of six human solid tumor cell lines has been investigated. The 2,5-dihydroxy-3-(3-methylbut-2-enyl)naphthalene-1,4-dione (4) and 2,3-dihydro-5-hydroxy-2-(prop-1-en-2-yl)naphtho[2,3-b]furan-4,9-dione (27) were the most potent antiproliferative agents with GI(50) values of 0.42-8.1 and 0.80-2.2microM, respectively. The results provide insight into the correlation between some structural properties of 5-hydroxynaphthoquinones and their antiproliferative activity.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Naftoquinonas/química , Naftoquinonas/síntese química , Naftoquinonas/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indicadores e Reagentes , Lipídeos/química , Espectroscopia de Ressonância Magnética , Prenilação , Relação Estrutura-AtividadeRESUMO
The introduction of a hemisuccinate group at the 21-position of the passive antiglucocorticoid 21OH-6,19OP leads to a compound (21HS-6,19OP) with a notable activity profile toward the glucocorticoid receptor (GR). In contrast to the parent steroid, 21HS-6,19OP behaves as a pure agonist of GR activity in direct transactivation assays. However, the apoptotic effects of 21HS-6,19OP show that the effect depends on cell type: while 21HS-6,19OP is a pure agonist in L929 mouse fibroblasts, in thymocytes 21HS-6,19OP had significant antiglucocorticoid activity. This tissue-specific activity makes 21HS-6,19OP a novel selective GR modulator. To investigate the molecular basis of action of 21HS-6,19OP, we carried out molecular dynamics simulations (6 ns) of the GR ligand binding domain (LBD) complexed with 21HS-6,19OP. Our results indicate that the hemisuccinate moiety may play a key role in stabilizing the active conformation of the receptor dimerization interface, reverting the changes observed with the antagonist 21OH-6,19OP. Other changes in regions of the GR related to cofactor recruitment (possibly tissue-specific), could explain this particular activity profile.
Assuntos
Progesterona/análogos & derivados , Receptores de Glucocorticoides/agonistas , Animais , Apoptose , Células COS , Chlorocebus aethiops , Simulação por Computador , Dimerização , Genes Reporter , Humanos , Camundongos , Progesterona/química , Progesterona/farmacologia , Progestinas/química , Progestinas/farmacologia , Receptores de Glucocorticoides/química , Relação Estrutura-AtividadeRESUMO
Eudesmane-type sesquiterpenoids 3alpha-(2,3-epoxy-2-methylbutyryloxy)-4alpha-formoxy-11-hydroxy-6,7-dehydroeudesman-8-one (1) and 3alpha-(2,3-epoxy-2-methylbutyryloxy)-4alpha,7alpha,11-trihydroxyeudesman-8-one (2), together with 10 known structurally related eudesmanes were isolated from the CHCl3 extract of aerial parts of Pluchea sagittalis (Lamarck) Cabrera. Their structures were deduced by extensive application of 1 and 2D NMR spectroscopic techniques and high and low resolution CIMS. X-ray crystallographic analysis of the known compound 3alpha-(2,3-epoxy-2-methylbutyryloxy)-4alpha-formoxycuauthemone (9) is reported here for the first time, and confirms the structural features for the series of the reported eudesmanes. All eudesmanes were tested for their antifeedant activity by incorporating them to an artificial diet of larvae of the polyphagous insect Spodoptera frugiperda at a concentration of 100ppm. Our results, from feeding choice tests, indicated that most of the compounds deter larval feeding at the cited concentration.
Assuntos
Asteraceae/química , Comportamento Alimentar/efeitos dos fármacos , Preparações de Plantas/farmacologia , Sesquiterpenos de Eudesmano/farmacologia , Sesquiterpenos/farmacologia , Spodoptera/efeitos dos fármacos , Animais , Cristalografia por Raios X , Larva/efeitos dos fármacos , Estrutura Molecular , Componentes Aéreos da Planta/química , Preparações de Plantas/química , Sesquiterpenos/síntese química , Sesquiterpenos/química , Sesquiterpenos de Eudesmano/síntese química , Sesquiterpenos de Eudesmano/químicaRESUMO
Six new trechonolide type withanolides (compounds 1- 6), together with trechonolide A, jaborotetrol, and 12- O-methyl jaborosotetrol, were isolated from the aerial parts of Jaborosa laciniata. The structures were elucidated on the basis of spectroscopic methods (1D and 2D NMR, MS).