RESUMO
Phytochemical investigation of the 70% acetone extract of Croton crassifolius roots afforded eight new diterpenoids, crassins A-H (1-8), and 19 known compounds. The structures of the new compounds were determined by spectroscopic methods, and their absolute configurations were determined by electronic circular dichroism, single-crystal X-ray diffraction analysis, comparison with literature data, and biogenetic considerations. Crassins A (1) and B (2) are new ring B-rearranged diterpenoids, whereas crassin C (3) is a new ring A-rearranged diterpenoid. Crassin H (8) exhibited selective cytotoxicity against A549 cells (IC50 5.2 µM) compared with HL-60 cells (IC50 11.8 µM). The known compound chettaphanin-II exhibited moderate activity against the A549 and HL-60 cell lines (IC50 8.4 and 10.5 µM, respectively).
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Croton/química , Diterpenos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Raízes de Plantas/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Diterpenos/química , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células HL-60 , Humanos , Concentração Inibidora 50 , Conformação Molecular , Estrutura MolecularRESUMO
Investigation of hydrophobic extract of Dichondra repens (Convolvulaceae) led to the isolation of three new resin glycosides dichondrins A-C (1-3), and three known resin glycosides cus-1, cus-2, and cuse 3. All the isolated resin glycosides with an acyclic core were evaluated for their multidrug resistance reversal activities, and the combined use of these compounds at a concentration of 25µM increased the cytotoxicity of vincristine by 1.03-1.78-fold.
Assuntos
Glicosídeos/química , Glicosídeos/farmacologia , Poaceae/química , Resinas Vegetais/química , Resinas Vegetais/farmacologia , Sequência de Carboidratos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Humanos , Células KB , Dados de Sequência Molecular , Folhas de Planta/química , Vincristina/farmacologiaRESUMO
A directing-group-assisted copper-catalyzed oxidative esterification of phenols with aldehydes using TBHP as an oxidant was described. This methodology which showed the advantages of base, ligand free, short routes and functional group tolerance could be used as an alternative protocol for the classical esterification reactions.
Assuntos
Aldeídos/química , Cobre/química , Fenóis/química , Catálise , Esterificação , Oxidantes/química , Oxirredução , Peróxidos/químicaRESUMO
A ruthenium-catalyzed oxidative coupling of 2-aryl-quinazolinones with olefins via C-H bond activation followed by an intramolecular aza-Michael reaction is described. This strategy allows the direct and efficient construction of pyrrolo[2,1-b]quinazolin-9(1H)-one scaffolds.
Assuntos
Alcenos/química , Acoplamento Oxidativo , Quinazolinonas/síntese química , Rutênio/química , Catálise , Técnicas de Química Sintética , Quinazolinonas/químicaRESUMO
Five new pentasaccharide resin glycosides, named merremins A-E (1-5), two new pentasaccharide resin glycoside methyl esters, named merremins F and G (6, 7), and four known resin glycosides, murucoidin IV, murucoidin V, stoloniferin IV, and murucoidin XVII, were obtained from the aerial parts of Merremia hederacea. This is the first report of resin glycosides obtained from M. hederacea. In addition, the new compounds can be divided into three types: those possessing an 18-membered ring (1-4), compound 5 with a 20-membered ring, and those with an acyclic core (6, 7). Furthermore, the different types of resin glycosides were evaluated for their multidrug resistance reversal activities. Compounds 1, 5, 6, and murucoidin V were noncytotoxic and enhanced the cytotoxicity of vinblastine by 2.3-142.5-fold at 25 µM. Compound 5 and murucoidin V, with 20-membered rings, were more active than compound 1, with an 18-membered ring.
Assuntos
Convolvulaceae/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Glicolipídeos/isolamento & purificação , Glicolipídeos/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Oligossacarídeos/isolamento & purificação , Oligossacarídeos/farmacologia , Resinas Vegetais/química , Medicamentos de Ervas Chinesas/química , Glicolipídeos/química , Glicosídeos/química , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oligossacarídeos/química , VimblastinaRESUMO
Phytochemical investigation of Cydonia oblonga Mill. collected in Xinjiang province, China, led to the isolation and identification of three new dibenzofurans (1-3) along with one known compound (4). Their structures were elucidated based on HRESIMS, spectroscopic data (IR, UV, 1D, 2D NMR) and X-ray diffraction analysis.
Assuntos
Dibenzofuranos/isolamento & purificação , Rosaceae/química , China , Dibenzofuranos/química , Estrutura Molecular , Análise Espectral , Difração de Raios XRESUMO
Phytochemical investigation of the 95% ethanol extract of the whole plant of Palhinhaea cernua afforded five new serratene-type triterpenoids (1-5) together with four known analogues (6-9). The structures of the new compounds were elucidated by extensive spectroscopic analysis and X-ray crystallographic data. Compounds 1-3 triggered apoptosis of Hela-/- cell with EC50 values of 3.49⯱â¯0.05, 0.28⯱â¯0.13 and 7.98⯱â¯0.03⯵M, respectively.
Assuntos
Lycopodiaceae/química , Triterpenos/isolamento & purificação , Apoptose , Cristalografia por Raios X , Células HT29 , Células HeLa , Humanos , Estrutura Molecular , Componentes Aéreos da Planta/químicaRESUMO
The phytochemical study of Euphorbia helioscopia afforded euphornin (1) in a large amount. Alkaline hydrolysis of 1 using potassium carbonate yielded the main product monodeacetyleuphornin (2), whose structural modification at 14-OH gave rise to 21 acylated derivatives euphornoate A-U (3-23). Thus, a mini compound library of jatrophanes was established to screen for MDR modulators. Biological studies clearly demonstrated the effect of C-14 pattern modification in MDR reversal activity and several compounds with RF values over 300 fold at 20⯵M (6, 16, 20, 22, 23) were thought to be promising MDR modulators. The SARs are discussed, which reveal that introduction of an alkyl acyl group bearing 4 carbons at C-14 or an aryl acyl group with electron donating groups is favorable for the activity.
Assuntos
Diterpenos/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Euphorbia/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Humanos , Células K562 , Componentes Aéreos da Planta/química , Relação Estrutura-AtividadeRESUMO
Chemical investigation of Euphorbia helioscopia resulted in the identification of seven new triterpenes named euphorbatrine A-G (1-7), including two (19αH)-lupane (1-2) and three (9ßH)-lanostane (4-6), which are very rare metabolites from plants. Their structures were elucidated by extensive spectroscopic analysis, X-ray crystallography and chemical methods. Compounds 5 and 6 triggered apoptosis of Hela-/- cell with EC50 values of 1.59±0.25 and 26.48±0.78µM, respectively.
Assuntos
Apoptose , Euphorbia/química , Triterpenos/isolamento & purificação , Células HeLa , Humanos , Estrutura Molecular , Componentes Aéreos da Planta/química , Triterpenos/farmacologiaRESUMO
The phytochemical study of Euphorbia helioscopia led to the isolation of 33 jatrophane diterpenoids (1-33), of which six (1-6) were new. This small jatrophane library was established to screen for potential lipid modulators. LDL-Uptake screening assay demonstrated that most of them improved LDL-Uptake rate in HepG2 cells, with compounds 16, 21 and 26 exhibiting more outstanding effects. Further exploration found that these three compounds could increase LDLR protein level in HepG2 cells dose-dependently. SAR studies suggested that substituted patterns of C-9, steric hindrance between C-14 and C-15, and the long conjugated fragment from C-5 to the carbonyl (C-9) were essential for the activity. Moreover, compound 21, a relatively abundant chemical in E. helioscopia, showed remarkable lipid-lowering effect in vivo, which makes it a promising lead for development of new lipid-lowering agents.
Assuntos
Diterpenos/isolamento & purificação , Euphorbia/química , Hipolipemiantes/isolamento & purificação , Lipoproteínas LDL/sangue , Animais , Diterpenos/farmacologia , Células Hep G2 , Humanos , Hipolipemiantes/farmacologia , Lipídeos/sangue , Lipoproteínas LDL/metabolismo , Mesocricetus , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Resin glycosides represent an important chemotaxonomic marker of the Convolvulaceae family and possess multidrug resistance (MDR) reversal activity. In our recent study, nine previously undescribed resin glycosides, Calonyctins B-J, were isolated from the seeds of Ipomoea muricata. Their structures with the absolute configuration were established on the basis of comprehensive spectroscopic analysis and chemical methods. Among these, Calonyctins F-I possessed a skeleton in which the aglycone moiety and the oligosaccharide core were linked by a 3-hydroxy-2-methylbutanoic acid moiety to form a 25-membered macrocyclic structure. Calonyctins E, J, and muricatic acid C methyl ester were non-cytotoxic but enhanced the cytotoxicity of vincristine by 2.5-407.1 fold at 25⯵M in KB/VCR cells. Calonyctin E was the most active one.
Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Ipomoea/química , Resinas Vegetais/isolamento & purificação , Resinas Vegetais/farmacologia , Sementes/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Glicosídeos/química , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Resinas Vegetais/química , Vimblastina/farmacologia , Vincristina/farmacologiaRESUMO
A new patchoulane-type sesquiterpenoid glycoside (1), together with five known sesquiterpenoids (2-6), was isolated from the roots of Croton crassifolius. Their structures were elucidated on the basis of spectroscopic methods. This is the first report about the sesquiterpenoid glycoside from C. crassifolius. All the isolated compounds 1-6 were evaluated for their cytotoxic activities against human tumour cell lines HL-60 and A549, but none showed significant activity.
Assuntos
Croton/química , Glicosídeos/isolamento & purificação , Raízes de Plantas/química , Sesquiterpenos/isolamento & purificação , Células A549 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Glicosídeos/química , Glicosídeos/farmacologia , Células HL-60 , Humanos , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Análise EspectralRESUMO
Phytochemical investigation of the 70% acetone extract of the whole plant of Scutellaria barbata D. Don afforded six new neo-clerodane diterpenoids, scubatines A-F (1-6), and four known analogues (7-10). Their structures were elucidated on the basis of extensive spectroscopic analyses. Cytotoxic activity against the HL-60 and A549 cell lines was assessed for all isolated compounds. Compound 9 exhibited moderate activity against HL-60 with an IC50 value of 5.6µM. Compound 6 showed weak cytotoxic activity against A549 and HL-60 with IC50 values of 10.4 and 15.3µM, respectively.
Assuntos
Antineoplásicos Fitogênicos/química , Diterpenos Clerodânicos/química , Scutellaria/química , Células A549 , Antineoplásicos Fitogênicos/isolamento & purificação , Diterpenos Clerodânicos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Estrutura MolecularRESUMO
IspH is a key enzyme in the last step of the methyl-D-erythritol-4-phosphate (MEP) pathway. Loss of function of IspH can often result in complete yellow or albino phenotype in many plants. Here, we report the characterization of a recessive mutant of maize, zebra7 (zb7), showing transverse green/yellow striped leaves in young plants. The yellow bands of the mutant have decreased levels of chlorophylls and carotenoids with delayed chloroplast development. Low temperature suppressed mutant phenotype, while alternate light/dark cycle or high temperature enlarged the yellow section. Map-based cloning demonstrated that zb7 encodes the IspH protein with a mis-sense mutation in a conserved region. Transgenic silencing of Zb7 in maize resulted in complete albino plantlets that are aborted in a few weeks, confirming that Zb7 is important in the early stages of maize chloroplast development. Zb7 is constitutively expressed and its expression subject to a 16-h light/8-h dark cycle regulation. Our results suggest that the less effective or unstable IspH in zb7 mutant, together with its diurnal expression, are mechanistically accounted for the zebra phenotype. The increased IspH mRNA in the leaves of zb7 at the late development stage may explain the restoration of mutant phenotype in mature stages.
Assuntos
Clonagem Molecular , Eritritol/análogos & derivados , Proteínas de Plantas/genética , Fosfatos Açúcares/biossíntese , Zea mays/enzimologia , Sequência de Aminoácidos , Vias Biossintéticas , Cloroplastos/enzimologia , Cloroplastos/genética , Mapeamento Cromossômico , Eritritol/biossíntese , Hemiterpenos/metabolismo , Indóis/metabolismo , Dados de Sequência Molecular , Compostos Organofosforados/metabolismo , Proteínas de Plantas/metabolismo , Alinhamento de Sequência , Zea mays/genética , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismoRESUMO
Understanding the inheritance of resistance to Fusarium ear rot is a basic prerequisite for an efficient resistance breeding in maize. In this study, 250 recombinant inbred lines (RILs) along with their resistant (BT-1) and susceptible (N6) parents were planted in Zhengzhou with three replications in 2007 and 2008. Each line was artificially inoculated using the nail-punch method. Significant genotypic variation in response to Fusarium ear rot was detected in both years. Based on a genetic map containing 207 polymorphic simple sequence repeat (SSR) markers with average genetic distances of 8.83 cM, the ear rot resistance quantitative trait loci (QTL) were analyzed by composite interval mapping with a mixed model (MCIM) across the environments. In total, four QTL were detected on chromosomes 3, 4, 5, and 6. The resistance allele at each of these four QTL was contributed by resistant parent BT-1, and accounted for 2.5-10.2% of the phenotypic variation. However, no significant epistasis interaction effect was detected after a two-dimensional genome scan. Among the four QTL, one QTL with the largest effect on chromosome 4 (bin 4.06) can be suggested to be a new locus for resistance to Fusarium ear rot, which broadens the genetic base for resistance to the disease and can be used for further genetic improvement in maize-breeding programs.