RESUMO
One new bisabolane-type sesquiterpenoid, together with four known bisabolane-type sesquiterpenoid derivatives and seven phenolics, was isolated from the rhizomes of Curcuma longa. Their structures were elucidated by extensive spectroscopic (IR, HR-ESI-MS, and NMR) data analysis. The possible anti-Alzheimer's disease (AD) activities of the isolated compounds were also evaluated using Caenorhabditis elegans AD pathological model, and 1ß-hydroxybisabola-2,10-dien-4-one had the highest possible anti-AD activity.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Curcuma/química , Sesquiterpenos Monocíclicos/farmacologia , Fenóis/farmacologia , Rizoma/química , Animais , Caenorhabditis elegans , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estrutura Molecular , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Eupulcherol A (1), a novel triterpenoid with an unprecedented carbon skeleton, was isolated from Euphorbia pulcherrima. Its structure was determined by comprehensive analysis of spectroscopic data, including HRESIMS and 1D and 2D NMR, and the absolute configuration was defined by single crystal X-ray diffraction analysis. Biological studies showed that compound 1 possessed anti-Alzheimer's disease (AD) bioactivity, which could delay paralysis of transgenic AD Caenorhabditis elegans. A plausible biogenetic pathway for eupulcherol A (1) was also proposed.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Antiprotozoários/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Euphorbia/química , Triterpenos/farmacologia , Doença de Alzheimer/parasitologia , Animais , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Relação Dose-Resposta a Droga , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Nardochinins A-D (1-4), four novel sesquiterpenoids, along with four known ones were isolated from the underground parts of Nardostachys chinensis Batal in ethanol. Their structures were determined by extensive spectroscopic methods and single-crystal X-ray diffraction. Nardochinin A (1) possessed a norsesquiterpene skeleton with an unusual 3/6/5/5 tetracyclic ring system, which had not appeared in natural products. Nardochinins B (2) and C (3) were the first time found naturally occurring sesquiterpenoids with a 4,5-seco-nardosinane skeleton. Besides, compound 3 represented an unprecedented 4,5-seco-nardosinane type norsesquiterpenoid with losing an isopropenyl at C-6 compared with 2 in the structural framework. Nardochinin D (4) was a novel, highly oxygenated valerenane-type sesquiterpenoid possessing a rare 3,12-epoxy group and an unusual 9,11-epoxy group. The anti-Alzheimer's disease (AD) activities of 1-4 were also evaluated using the Caenorhabditis elegans AD pathological model, and nardochinin B (2) had the highest anti-AD activity.
RESUMO
A novel C16 tetranorditerpenoid, norcrassin A (1), and an unusual dimeric labdane-type diterpenoid, bicrotonol A (2), were isolated from the roots of Croton crassifolius. Norcrassin A (1) featured a new carbon skeleton with an unprecedented 5/5/5/6 tetracyclic system. Bicrotonol A (2) possessed an unusual tetrahydroxypyran ring linkage connecting two labdane diterpenoid monomers. The structures of all compounds, including the absolute configuration, were elucidated by the interpretation of their NMR spectroscopic data, high resolution mass spectrometry, and single-crystal X-ray diffraction. A plausible biosynthetic pathway of 1 is proposed. The anti-Alzheimer's Disease (AD) activities of 1 and 2 are also evaluated using the AD pathological model.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Croton/química , Diterpenos/química , Diterpenos/uso terapêutico , Raízes de Plantas/química , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Cristalografia por Raios X , Modelos Animais de Doenças , Diterpenos/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Modelos MolecularesRESUMO
A new eremophilane norsesquiterpenoid (1), together with a known eremophilane sesquiterpenoid (2), was isolated from the leaves of Ligularia virgaurea. The structure of 1 was elucidated by a combination of spectroscopic analysis (IR, 1D NMR, 2D NMR, and HR-ESI-MS), and its absolute configuration was determined by a single-crystal X-ray diffraction experiment (with copper radiation). The known compound 2 was identified by comparison of its physical and spectral data with those reported in the literature. Compound 1 was assayed for its cytotoxic activities against human cervical carcinoma cell (HeLa) and human small cell lung cancer cell (NCI-446) lines.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Asteraceae/química , Sesquiterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Salvia has been regarded as a beneficial healing herb in ancient Egypt, Rome and Greece, and is listed as an official medicine in the pharmacopoeias of many countries worldwide. Currently, Salvia is widely used to flavor and preserve food. Here, two undescribed norabietane-type diterpenoids, sadigitaloides A and B, two undescribed germacrane-type sesquiterpenoids, sadigitaloides C and D, five undescribed guaiane-type sesquiterpenoid lactones, sadigitaloides E-I, two undescribed noreudesmane-type sesquiterpenoids, sadigitaloides J and K, one known diterpenoid, three known sesquiterpenoids, and three other types of known compounds were isolated from the 95% ethanol extract of the whole plants of Salvia digitaloides. Their structures and absolute configurations were characterized using 1D and 2D NMR spectroscopic techniques, electronic circular dichroism (ECD) calculations, HRESIMS experiments, and single-crystal X-ray diffraction analysis. Some compounds were evaluated for their anti-inflammatory activities against lipopolysaccharide (LPS)-induced TNF-α production in rat macrophage NR8383 cells. Sadigitaloide A showed noticeable anti-inflammatory activity at a concentration of 100.0 µM. At a concentration of 60 µM, sadigitaloide B exhibited better protection of dopaminergic neurons than the positive control n-butylidenephthalide in the Caenorhabditis elegans model injured by 6-OHDA. The phytotoxic activities of some compounds were attributed to considerable inhibitory effects on the growth of the roots and hypocotyls of Raphanus sativus L seedlings, especially cis, trans-abscisic acid, whose inhibition rates were much higher than those of glyphosate at concentrations ranging from 50 to 400 ppm. These results indicated that abietane-type diterpenoids possessed excellent anti-inflammatory and neuroprotective activities and further suggested that the low-molecular-weight compounds exhibited outstanding phytotoxic activities.
Assuntos
Salvia , Animais , Ratos , Anti-Inflamatórios , GréciaRESUMO
Hydroxycinnamic acid derivatives (HCAs) are a group of naturally occurring polyphenolic compounds which possess various pharmacological activities. In this work, the interactions of bovine serum albumin (BSA) with six HCA derivatives, including chlorogenic acid (CHA), caffeic acid (CFA), m-coumaric acid (m-CA), p-coumaric acid (p-CA), ferulic acid (FA) and sinapic acid (SA) have been investigated by NMR spectroscopic techniques in combination with fluorescence and molecular modeling methods. Competitive STD NMR experiments using warfarin sodium and L-tryptophan as site-selective probes indicated that HCAs bind to site I in the subdomain IIA of BSA. From the analysis of the STD NMR-derived binding epitopes and molecular docking models, it was deduced that CHA, CFA, m-CA and p-CA show similar binding modes and orientation, in which the phenyl ring is in close contact with protein surface, whereas carboxyl group points out of the protein. However, FA and SA showed slightly different binding modes, due to the steric hindrance of methoxy-substituents on the phenyl ring. Relaxation experiments provided detailed information about the relationship between the affinity and structure of HCAs. The binding affinity was the strongest for CHA and ranked in the order CHA > CFA > m-CA ≥ p-CA > FA > SA, which agreed well with the results from fluorescence experiments. Based on our experimental results, we also conclude that HCAs bind to BSA mainly by hydrophobic interaction and hydrogen bonding. This study therefore provides valuable information for elucidating the mechanisms of BSA-HCAs interaction.
Assuntos
Ácidos Cumáricos/química , Ácidos Cumáricos/metabolismo , Soroalbumina Bovina/metabolismo , Animais , Sítios de Ligação , Bovinos , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Prótons , Soroalbumina Bovina/química , SoluçõesRESUMO
Viticis Fructus, known as "Man-jing-zi", are the fruits of the traditional Chinese medicine Vitex trifolia Linn. and its variant Vitex trifolia Linn. var. simplicifolia. These fruits are used as folk medicines to treat various diseases. Although V. trifolia is useful for treating diabetes, the antidiabetic effect of its purified constituents is still under investigation. The phytochemical investigation on the ethanol extract of the fruits of V. trifolia yielded four new labdane diterpenoids vitetrolins A-D (1-4), together with seven (5-11) known analogs. The structures of these compounds were elucidated by spectroscopy techniques and the absolute configuration of 4 was determined by electronic circular dichroism (ECD) calculations. The isolated diterpenoids were evaluated for their α-glucosidase inhibitory activities. Compounds 5, 6, 8, and 9 exhibited moderate inhibitory activities against α-glucosidase with IC50 values ranging from 44.9 ± 6.1 to 70.5 ± 5.5 µM.
Assuntos
Diterpenos , Inibidores de Glicosídeo Hidrolases , Vitex , Diterpenos/farmacologia , Frutas/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Estrutura Molecular , Vitex/química , alfa-GlucosidasesRESUMO
A new clerodane diterpenoid, crotolanin A (1), along with three known clerodane diterpenoids, crotoeurin B (2), teucvidin (3) and teucvin (4), was isolated from the ethanol extract of the leaves and twigs of Croton lachnocarpus Benth. Their structures were identified by extensive NMR spectroscopic and HRESIMS analyses. The dopaminergic neuroprotective activity of compounds 1-4 was tested by using transgenic Caenorhabditis elegans pathological model. Compound 2 alleviated dopaminergic neuron degeneration of worms induced by 6-hydroxydopamine (6-OHDA) that represented a potential therapy for Parkinson's disease (PD).
RESUMO
The ethanol extract of the roots of Codonopsis pilosula was subjected to chromatographic fractionation, which result in the isolation and characterization of two new aromatic derivatives 2,3-dihydroxypropyl 2,4-dihydroxy-3,6-dimethylbenzoate (1) and 2-oxopropyl 3-hydroxy-4-methoxybenzoate (2), along with three known compounds pilosulinene A (3), pollenfuran B (4) and (+)-pinoresinol (5). Their structures were demonstrated by HRESIMS and spectroscopic methods including NMR and IR. It is worth noting that compound 4 was isolated for the first time from the genus Codonopsis. The potential hypoglycemic properties of compounds 2-5 were evaluated by measuring their α-glucosidase inhibitory effects. As a result, compounds 2 and 3 showed weak α-glucosidase inhibitory activities with IC50 values of 154.8 ± 11.0 µM and 24.0 ± 2.2 µM, respectively.[Formula: see text].
Assuntos
Codonopsis , Codonopsis/química , Etanol , Hipoglicemiantes , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Triterpenos , alfa-GlucosidasesRESUMO
One novel diterpenoid lactone named caesalpinbondin A (1) that possesses an unprecedented tetracyclic ring system in which a 6/6/5-fused tricyclic ring and a 4,5-dimethyldihydrofuran-2(3H)-one were connected by a C-C single bond comprising a 5-(naphtho [2,3-b]furan-7-yl)dihydrofuran-2(3H)-one moiety was isolated from the seeds of Caesalpinia bonduc. Its chemical structure was established by extensive spectroscopic methods, and its absolute configuration was further determined by single-crystal X-ray diffraction analysis and electronic circular dichroism calculation. The biological evaluation suggested that compound 1 demonstrated potent anti-Alzheimer's disease (AD) bioactivity, which could delay paralysis of transgenic AD Caenorhabditis elegans. A possible biogenetic pathway of 1 was also proposed.
RESUMO
A new highly oxygenated germacranolide, carcerlane A (1), together with four known highly oxygenated germacranolides (2-5), was isolated from an ethanol extract of the whole plant of Carpesium nepalense var. lanatum (C.B.Clarke) Kitam. The structures were determined by HRESIMS and extensive analysis of their spectroscopic data including IR, 1 D and 2 D NMR spectra. To our best knowledge, it was the first time to report the phytochemical investigation on this plant. The anti-Alzheimer's disease (AD) activities of 1-5 were evaluated using Caenorhabditis elegans AD pathological model. All the tested compounds showed that they have the anti-AD bioactivities of delaying worms paralysis.
Assuntos
Antineoplásicos Fitogênicos , Asteraceae , Antineoplásicos Fitogênicos/química , Asteraceae/química , Estrutura Molecular , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologiaRESUMO
Salvia castanea (Family Labiatae), a perennial fragrant herb with castaneous flowers, is mainly distributed in areas with an altitude of 2500-3750 m. The roots of this plant were used as a tea drink by local residents to strengthen physical health. The aim of present study was to acquire secondary metabolites of the ethanol extract obtained from the whole plant of S. castanea and to evaluate their potential anti-Alzheimer's disease. Six new sesquiterpene lactones, salcastanins A-F (1-6), together with three known guaiane-type sesquiterpenoids nubiol (7), nubdienolide (8), and nubenolide (9), were separated from the whole plant of S. castanea. The structures of these compounds were determined by HRESIMS and NMR experiments. The absolute configurations of 1-6 were ascertained by electronic circular dichroism (ECD) experiments. The humanized Caenorhabditis elegans AD pathological model was used to evaluate anti-Alzheimer's disease (AD) activities of 1-9. The results showed the compounds 1-3 and 7 significantly delayed AD-like symptoms of worm paralysis phenotype, which could be used as novel anti-AD candidates.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Extratos Vegetais/química , Salvia/química , Sesquiterpenos/farmacologia , Animais , Caenorhabditis elegans/efeitos dos fármacos , China , Modelos Animais de Doenças , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Sesquiterpenos/isolamento & purificaçãoRESUMO
Commiphoins A-C (1-3), three new cadinane-type sesquiterpenes, together with two known cadinane-type sesquiterpenes (4 and 5) were isolated from the resinous exudates of Commiphora myrrha. Their structures and relative configurations were established on the basis of comprehensive spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses. Compounds 1 and 3-5 were screened for anti-Alzheimer's disease (AD) activities using the AD pathological model in Caenorhabditis elegans. The results showed that they all had significant anti-AD activities.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Commiphora/química , Sesquiterpenos Policíclicos/isolamento & purificação , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans , Avaliação Pré-Clínica de Medicamentos , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/uso terapêutico , Resinas Vegetais/químicaRESUMO
A general γ-C(sp2)-H iodination method directed by an aliphatic keto group has been developed under transition-metal-free conditions for the first time, generating iodoarenes in good to excellent yields with excellent site selectivity. This protocol features a wide range of aryl-substituted ketones, short reaction times, mild reaction conditions, and scalable synthetic procedures. A possible reaction mechanism was also proposed based on several control experiments.
RESUMO
A novel type of oxime phosphonate was synthesized and used in the intermolecular cascade radical addition reaction of alkenes to access ß-aminophosphonates via visible-light-driven N-centered iminyl radical-mediated and redox-neutral selective C-P single-bond cleavage in an active phosphorus radical route. The procedure is characterized by its ability to achieve the construction of Csp3-P and Csp3-N bonds without the requirement for oxidants and bases.
RESUMO
Narjatamanins A (1) and B (2), a pair of epimers possessing a novel 2,3-seco-iridoid skeleton with an unusual 1,10-oxygen bridge, were isolated from the whole plants of Nardostachys jatamansi. Their structures were elucidated by a combination of various spectroscopic methods, including HRESIMS, IR and 1D and 2D NMR techniques. The absolute configurations of 1 and 2 were established by electronic circular dichroism (ECD) calculations. The pharmacological activities of 1 and 2 to alleviate AD-like symptoms were also evaluated using the Caenorhabditis elegans Alzheimer's disease (AD) pathological model, and narjatamanins A (1) and B (2) showed statistically significant delay in the worm paralysis phenotype of AD-like symptoms.
RESUMO
A phytochemical study of the ethanolic extract of the leaves of Ligularia virgaurea led to the isolation of a new eremophilane-type sesquiterpene lactone, (4S,5R,6S,8S,lR)-6ß-angeloyloxy-eremophil-7(l l)-en-10ßH-8α,12-olide (1), along with a known eremophilane-type sesquiterpene, (4S,5R,6S,lOS)-6ß- angeloyloxy-10ßH-furanoeremophil-9-one (2). Their structures were elucidated by extensive spectroscopic methods, including ID and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry experiments, and the absolute configurations were confirmed by single-crystal X-ray diffraction analysis using the anomalous scattering of Cu Ka radiation.
Assuntos
Asteraceae/química , Folhas de Planta/química , Sesquiterpenos/química , Estrutura Molecular , Extratos Vegetais/químicaRESUMO
Three new iridoids, valejatanins A-C (1-3), and one new natrual iridoid (4), together with four known sesquiterpenoids (5-8), were isolated from the roots of Valeriana jatamansi Jones. Compounds 3 and 4 are C(4)-epimers. Their structures were elucidated by extensive spectroscopic analysis (IR, HRESIMS, 1D and 2D NMR) and by comparison of their NMR data with those of related compounds. The absolute configuration of 5 was determined for the first time by single-crystal X-ray diffraction analysis with Cu-Kα irradiation. The cytotoxic activities of all compounds were evaluated against HT29, K562 and B16 cancer cell lines in vitro by MTT assay. Valejatanin A (1) showed noteworthy cytotoxic activities with IC50 values of 22.17, 15.26, 3.53µg/mL against three cancer cell lines. The antibacterial activities of all compounds against bacteria were tested in vitro. Compound 6 exhibited antibacterial activities against Staphylococcus aureus and Pseudomonas aeruginosa.
Assuntos
Antibacterianos/química , Iridoides/química , Sesquiterpenos/química , Valeriana/química , Animais , Antibacterianos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Iridoides/isolamento & purificação , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Raízes de Plantas/química , Pseudomonas aeruginosa/efeitos dos fármacos , Sesquiterpenos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacosRESUMO
The fungus Clonostachys rosea is widely distributed all over the world. The destructive force of this fungus, as a biological control agent, is very strong to lots of plant pathogenic fungi. As part of the ongoing search for antibiotics from fungi obtained from soil samples, the secondary metabolites of C. rosea YRS-06 were investigated. Through efficient bioassay-guided isolation, three new bisorbicillinoids possessing open-ended cage structures, tetrahydrotrichodimer ether (1) and dihydrotrichodimer ether A and B (2 and 3), and 12 known compounds were obtained. Their structures were determined via extensive NMR, HR-ESI-MS, and CD spectroscopic analyses and X-ray diffraction data. Compounds 1-3 are rare bisorbicillinoids with a γ-pyrone moiety. The biological properties of 1-15 were evaluated against six different Gram-positive and Gram-negative bacteria. Bisorbicillinoids, 2-5, and TMC-151 C and E, 14 and 15, showed potent antibacterial activity.