RESUMO
Isogeopyxins A-C (1-3), three new diterpenoids with ent-kaurane, ent-pimarane, and ent-abietane scaffolds, respectively, along with six known ent-kauranoids, were isolated from the fermentation culture of Geopyxis sp. XY93 inhabiting the leaves of Isodon parvifolia. Their structures were elucidated by interpretation of spectroscopic data, and single crystal X-ray diffraction. It marks the first time that ent-kauranoids, characteristic metabolites of Isodon species, have been isolated from an associated endophytic fungus.
Assuntos
Antineoplásicos Fitogênicos , Ascomicetos , Diterpenos do Tipo Caurano , Diterpenos , Isodon , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Isodon/química , Estrutura MolecularRESUMO
Four new limonoids, named as trichiconlide G (1), 2-hydroxyltrijugin F (2), 23-oxo-21-hydroxyltrijugin F (3), 21-oxo-23-hydroxyltrijugin F (4), along with sixteen known analogues (5-20) were isolated from the leaves and twigs of Trichilia connaroides. Their structures and absolute configurations were determined by spectroscopic analyses, X-ray diffraction analysis, and TD-DFT-ECD calculations. Trichiconlide G (1) is one rare naturally occurring 1,2-seco phragmalin-type limonoid bearing a C-7/28 δ-lactone ring. Additionally, 2-hydroxyltrijugin F (2), 23-oxo-21-hydroxyltrijugin F (3), and 21-oxo-23-hydroxyltrijugin F (4) are three naturally occurring limonoids with a rare C-16/8 δ-lactone ring. All isolates were evaluated for their cytotoxic and anti-inflammatory activities. None of compounds exhibited cytotoxicity against five human cancer cell lines A-549, HepG2, 5-8F, Siha, and SCC-4 at the concentration of 40 µM. Compounds 16 and 17 showed moderate anti-inflammatory activity with IC50 values of 28.45 ± 2.51 and 22.66 ± 2.01 µM, respectively.
Assuntos
Anti-Inflamatórios/farmacologia , Limoninas/farmacologia , Meliaceae/química , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , China , Humanos , Limoninas/isolamento & purificação , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Células RAW 264.7RESUMO
Whole plants of Gentianella turkestanorum are commonly used as a traditional Uighur medicine. A phytochemical investigation led to the isolation of eight undescribed gentianellane-type sesterterpenoids (18-epi-nitidasin, gentianelloids D-F, and 18-epi-gentianelloids C-F), one undescribed 11,12-seco-gentianellane (18-epi-alborosin), and three known analogs (nitidasin, gentianelloid C and alborosin) among which gentianelloid C was found for the first time from a natural source. The structures of these compounds were elucidated by extensive spectroscopic analyses (including 1D and 2D NMR, HRMS, IR, and specific rotation) and in the case of 18-epi-gentianelloid C by the single-crystal X-ray diffraction analysis. A putative biosynthetic route for these sesterterpenoids was proposed. The immunosuppressive activity of the isolated compounds was also evaluated by their ability to inhibit the proliferation of T cells and T cell cytokine IFN-γ production. Nitidasin suppressed IFN-γ production with an IC50 value of 16.50 µM, while gentianelloid F and alborosin inhibited the proliferation of and IFN-γ production in T cells with IC50 values of 12.40-14.66 µM.
Assuntos
Gentianella , Espectroscopia de Ressonância Magnética , Medicina Tradicional , Estrutura Molecular , Compostos FitoquímicosRESUMO
Five new compounds, including a pair of diphenylcyclopentenone enantiomers (±)-phomopsisin A (1), a sesquiterpenoid 15-hydroxylithocarin A (2), a new diketopiperazine alkaloid prenylcyclotryprostatin A (3) and 7-hydroxy-cis-L(-)-3,6-dibenzyl-2,5-dioxopiperazine (6), along with five known compounds were isolated from the fungus Phomopsis asparagi. Their structures were elucidated on the basis of spectroscopic analyses (1D and 2D NMR), theoretical electronic circular dichroism (ECD) calculation, modified Mosher's method, and X-ray crystallography. The racemates of (±)-phomopsisin A showed inhibition on α-glucosidase with IC50 of 30.07 ± 0.75 µM (positive control acarbose, 121 ± 2.7 µM).
Assuntos
Alcaloides/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Phomopsis/química , Sesquiterpenos/farmacologia , Alcaloides/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Sesquiterpenos/isolamento & purificaçãoRESUMO
Eleven undescribed schinortriterpenoids (SNTs) and one known analogue (12) were isolated from the stems and leaves of Schisandra henryi. Their diverse structures included preschisanartane (1), 18-norschiartane (2-5, 12), schiartane (6 and 7), and schisanartane (8-11) skeletons, which were elucidated by comprehensive NMR, MS, electronic circular dichroism analyses, single crystal X-ray diffraction and biogenetic considerations. 1 was the first case of preschisanartane-type SNT with six-membered lactone ring, and 2 was one of the most highly oxygenated 18-norschiartane SNTs. Three types of the highly oxygenated SNTs, 1, 4, 10 and 11, effectively prevent apoptosis induced by corticosterone in PC12 cells. In addition, 11 showed neurite outgrowth-promoting activity.
Assuntos
Fármacos Neuroprotetores/química , Extratos Vegetais/química , Folhas de Planta/química , Caules de Planta/química , Schisandra/química , Triterpenos/química , Animais , Corticosterona/metabolismo , Avaliação Pré-Clínica de Medicamentos , Humanos , Lactonas/química , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Oxigênio/química , Células PC12 , Ratos , Triterpenos/farmacologiaRESUMO
Ganoderma resinaceum is a multi-purpose herbal medicine that is homologous to functional food that has long been used for enhancing health and treating chronic hepatopathy in Traditional Chinese Medicine. In a search program to discover the key bioactive composition of G. resinaceum, sixteen new lanostane-type triterpenoids (1-16), and twenty known analogues (17-36) were isolated from the fruiting bodies of G. resinaceum. Spectroscopic analyses and X-ray crystallography were used to determine the new structures. Furthermore, the spectroscopic properties of 15ß-hydroxy-4,4,14α- trimethyl-3,7,11,20-tetraoxo-5α-pregn-8-ene (15) and 15α-hydroxy-4,4,14α-trimethyl- 3,7,11,20-tetraoxo-5α-pregn-8-ene (34) indicated a potential structural misassignment of their analogues, lucidone E and lucidone H, reported previously. To probe this hypothesis, ROESY experiments and single-crystal X-ray diffraction analysis were conducted. These results undoubtedly reassigned the structure of lucidone E and lucidone H. Biological evaluation of the selected compounds disclosed that compounds 3, 4, 7/21, 11, 12, 13/14, 17, 18, 24/25, 27, 30, 31, and 35 had significant hepatoprotective activities, due to their remarkable in vitro inhibitory activities against the increase of ALT and AST levels in HepG2 cells induced by H2O2.
Assuntos
Ganoderma/química , Fígado/efeitos dos fármacos , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Cristalografia por Raios X , Células Hep G2 , Humanos , Peróxido de Hidrogênio/metabolismo , Fígado/citologia , Fígado/enzimologia , Fígado/metabolismo , Modelos Moleculares , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/isolamento & purificação , Triterpenos/isolamento & purificaçãoRESUMO
Six new ent-kaurane diterpenoids, isorugosiformins A-F (1-6), were isolated from the aerial parts of Isodon rugosiformis Hand.-Mazz. Hara. Their structures were elucidated by spectroscopic data interpretation, single crystal X-ray diffraction, and quantum chemical calculation of NMR parameters. The absolute configuration of 5 as 6R was the first case in the known 6,7:8,15-diseco-7,20-olide-6,8-cyclo-ent-kaurane diterpenoids.
Assuntos
Diterpenos do Tipo Caurano/isolamento & purificação , Isodon/química , Animais , Linhagem Celular Tumoral , Diterpenos do Tipo Caurano/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Células RAW 264.7RESUMO
Dactylicapnosines A (1) and B (2), two reconstructed aporphines with unprecedent five-membered carbon ring D, were isolated from Dactylicapnos scandens, in which dactylicapnosine A showed potent anti-inflammatory bioactivity in vitro. Inspired by its biosynthetic pathway, the total synthesis of dactylicapnosine A via 10 steps has been achieved and afforded enough material to prove its significant anti-inflammatory effect in vivo.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Aporfinas/farmacologia , Papaveraceae/química , Extratos Vegetais/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Aporfinas/química , Aporfinas/isolamento & purificação , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/biossíntese , Camundongos , Estrutura Molecular , Dor/tratamento farmacológico , Dor/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Receptores de Prostaglandina E/antagonistas & inibidores , Receptores de Prostaglandina E/biossíntese , Estereoisomerismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Nineteen preschisanartane-type schinortriterpenoids (SNTs), among which eleven ones were previously undescribed, were isolated from two Schisandra species, S. sphaerandra and S. rubriflora. Their structures were determined using 1D and 2D NMR spectroscopic analyses, NMR data comparison, quantum chemical calculation of NMR parameters, electronic circular dichroism (ECD), X-ray single crystal diffraction, and chemical derivation. Furthermore, structural re-examination of a few previously reported preschisanartane-type SNTs led to the structural revision of preschisanartanin J. Besides, it is suggested that the reported structures of arisanlactone D and schilancidilactone W should be re-checked. Finally, a few isolated SNTs were found to possess neurite outgrowth-promoting activities, and protective activities against neural injuries.
Assuntos
Schisandra/química , Triterpenos/química , Triterpenos/isolamento & purificação , China , Dicroísmo Circular , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Componentes Aéreos da Planta/químicaRESUMO
Flavipesines A and B (1 and 2) and asperchalasines E-H (3-6), two cytochalasans with an unusual ring system and four merocytochalasans possessing a 5/6/11/5/5/6 ring system, were isolated from Aspergillus flavipes, along with three related compounds (7-9). Their structures, including absolute configurations, were determined on the basis of data from HRESIMS, NMR, ECD, molecular modeling, and single-crystal X-ray diffraction. Flavipesines A and B (1 and 2) represent the first examples of cytochalasans possessing a 5/6/7/6 ring system with a C-18-O-C-21 bridge. Compounds 3, 7, and 9 show moderate inhibitory activities against isocitrate dehydrogenase 1 (IDH1). This is the first report on the IDH1 inhibitory activities of cytochalasans.
Assuntos
Aspergillus/química , Citocalasinas/química , Simulação por Computador , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Isocitrato Desidrogenase/antagonistas & inibidores , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Difração de Raios XRESUMO
Four new ent-abietane diterpenoids, isoforrethins A-D (1-4), were isolated from the aerial parts of Isodon forrestii var. forrestii by a variety of chromatographic techniques. Their structures were elucidated on the basis of spectroscopic data interpretation, single crystal X-ray diffraction, and quantum chemical calculation. All of these compounds were evaluated for their cytotoxicity against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and compound 4 showed significant inhibitory activities against SMMC-7721, A-549, MCF-7, and SW-480.
Assuntos
Abietanos/farmacologia , Isodon/química , Abietanos/isolamento & purificação , Antineoplásicos Fitogênicos , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/químicaRESUMO
Two new ent-clerodane diterpenoids, named isoscoparins R and S (1 and 2), were isolated from the aerial parts of Isodon scoparius. Their structures were characterized mainly by analyzing the NMR and HRESIMS data, and the relative configuration of compound 1 was determined by single-crystal X-ray diffraction. Compound 2 showed weak activity as an autophagic inhibitor.
Assuntos
Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/farmacologia , Isodon/química , Antineoplásicos Fitogênicos/química , Autofagia/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Células HEK293 , Células HeLa , Humanos , Imunossupressores/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Componentes Aéreos da Planta/química , Espectrometria de Massas por Ionização por Electrospray , Difração de Raios XRESUMO
Phytochemical investigation on Hemiphragma heterophyllum led to the isolation of two new compounds, heterophyllumin A (1) and heterophylliol (3), along with nine known compounds, (â)-sibiricumin A (2), iridolactone (4), jatamanin A (5), dihydrocatalpolgenin (6), 25-hydroperoxycycloart-23-en-3ß-ol (7), 24-methylenecycloartanol (8), (+)-pinoresinol (9), hexadec-(4Z)-enoic acid (10), and 9,12, 15-octadecatrienoic acid (11). Their structures were elucidated on the basis of detailed spectroscopic analyses and by comparison with literature data. Further, the structure of compound 3 was unambiguously confirmed by single-crystal X-ray analysis. Some of those compounds showed moderate activity in the α-glucosidase inhibition assay.
Assuntos
Iridoides/química , Lignanas/química , Scrophulariaceae/química , Compostos de Espiro/química , Medicamentos de Ervas Chinesas , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Iridoides/farmacologia , Lignanas/farmacologia , Modelos Moleculares , Estrutura Molecular , Extratos Vegetais/química , Compostos de Espiro/farmacologia , Difração de Raios XRESUMO
Fifteen new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforatones A-O (1-15), along with 3 structurally related analogues (16-18), were isolated from the stems and leaves of Hypericum perforatum. Their structures and absolute configurations were established by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD), modified Mosher's methods, Rh2(OCOCF3)4- and [Mo2(OAc)4]-induced ECD, X-ray crystallography, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Compound 5 was found to be the first PPAP decorated by a rare 2,2,4,4,5-(pentamethyltetrahydrofuran-3-yl)methanol moiety and an oxepane ring. Furthermore, the isolates were screened for their acetylcholinesterase (AChE) and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities. Compounds 5, 10, 11, and 15 showed desirable AChE inhibitory activities (IC50 6.9-9.2 µM) and simultaneously inhibited BACE1 (at a concentration of 5 µM) with inhibition rates of 50.3%, 34.3%, 47.2%, and 34.6%, respectively. Interestingly, compound 5 showed the most balanced inhibitory activities against both AChE and BACE1 of all the tested compounds, which means that 5 could serve as the first valuable dual-targeted PPAP for the treatment of Alzheimer's disease. Preliminary molecular docking studies of 5 with BACE1 and AChE were also performed.
Assuntos
Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Hypericum/química , Floroglucinol/química , Floroglucinol/farmacologia , Compostos Policíclicos/química , Prenilação , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/química , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Ácido Aspártico Endopeptidases/química , Ácido Aspártico Endopeptidases/metabolismo , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/uso terapêutico , Simulação de Acoplamento Molecular , Floroglucinol/metabolismo , Floroglucinol/uso terapêutico , Conformação ProteicaRESUMO
Nine new ent-kaurane diterpenoids, named scopariusols L-T (1-9), were isolated from the aerial parts of Isodon scoparius. Their structures were characterized mainly by analyzing the NMR and HR-ESI-MS data, and the absolute configuration of 1 was determined by single-crystal X-ray diffraction. Compound 1 was active against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with an IC50 value of 0.6 µmol·L-1.
Assuntos
Antineoplásicos Fitogênicos/química , Diterpenos do Tipo Caurano/química , Medicamentos de Ervas Chinesas/química , Isodon/química , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Cristalografia por Raios X , Diterpenos do Tipo Caurano/isolamento & purificação , Diterpenos do Tipo Caurano/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Células HL-60 , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Componentes Aéreos da Planta/química , Células RAW 264.7RESUMO
Pepluanols C and D (1 and 2), featuring unprecedented 5/5/10 with out,out-[7.2.1]bicylcododecane core and 6/6/7/3 fused-ring skeletons, respectively, were isolated from Euphorbia peplus. Their chemical structures and absolute configurations were determined by a series of extensive spectroscopic methods, and X-ray diffraction analysis. In addition, pepluanols C and D showed 31.6 ± 8.3% and 30.5 ± 2.8% peak current inhibition on the Kv1.3 potassium channel at 30 µM.
Assuntos
Euphorbia/química , Cristalografia por Raios X , Diterpenos , Medicamentos de Ervas Chinesas , Estrutura MolecularRESUMO
Three new cleistanthane diterpenoids, phyllanglins A-C (1-3), a new natural product, 4-acetyl-bergenin (4), and three known compounds (5-7) were isolated from the roots of Phyllanthus glaucus. Their structures were elucidated by extensive spectroscopic data analyses and single-crystal X-ray diffraction. Phyllanglins A-C were unusual cleistanthane diterpenoids with phenylacetylene moieties, and a plausible biogenetic pathway was proposed to discuss the origins of them. All of the isolates were evaluated for their anti-inflammatory activities.
Assuntos
Acetileno/análogos & derivados , Diterpenos/isolamento & purificação , Phyllanthus/química , Raízes de Plantas/química , Acetileno/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Cristalografia por Raios X , Diterpenos/farmacologia , Camundongos , Estrutura Molecular , Células RAW 264.7RESUMO
Four new indole alkaloids, melodinusines A-D (1, 2, 6, and 7), along with 26 known indole alkaloids, were isolated from Melodinus tenuicaudatus and Melodinus khasianus (Melodinus genus). Among them, 1 and 2 are aspidospermine-aspidospermine-type bisindole alkaloids while 7 is a novel melodinus-type alkaloid. Their structures were established on the basis of comprehensive spectroscopic data analysis and the structure of 7 was further confirmed by single-crystal X-ray diffraction analysis. Their cytotoxic activities against five human cancer cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW480 were also evaluated.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Apocynaceae/química , Alcaloides Indólicos/isolamento & purificação , Quinolinas/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Frutas/química , Humanos , Alcaloides Indólicos/farmacologia , Estrutura Molecular , Componentes Aéreos da Planta/química , Quinolinas/farmacologiaRESUMO
Five new schinortriterpenoids, propinqtrilactones A and B (1 and 2) with rare lancischiartane scaffold, and propindilactones V-X (3-5), were isolated from the stems and leaves of Schisandra propinqua var. propinqua. Their structures were elucidated on the basis of comprehensive spectroscopic and mass spectrometric analysis. The absolute configurations of 1-5 were determined by CD methods, X-ray diffraction analysis and theoretical calculations. 4 was tested for its cytotoxic activities against five human tumor cell lines.
Assuntos
Schisandra/química , Triterpenos/isolamento & purificação , Linhagem Celular Tumoral , Dicroísmo Circular , Cristalografia por Raios X , Humanos , Estrutura Molecular , Folhas de Planta/química , Caules de Planta/químicaRESUMO
Seven new polyoxygenated cyclohexenoids, namely, phomopoxides A-G (1-7), were isolated from the fermentation broth extract of an endophytic fungal strain Phomopsis sp. YE3250 from the medicinal plant Paeonia delavayi Franch. The structures of these compounds were established by spectroscopic interpretation. The absolute configurations of compounds 1 and 4 were confirmed by X-ray crystallographic analysis and chemical derivative approach. All isolated compounds showed weak cytotoxic activities toward three human tumor cell lines (Hela, MCF-7, and NCI-H460) and weak antifungal activities against five pathogenic fungi (Candida albicans, Aspergillus niger, Pyricularia oryzae, Fusarium avenaceum, and Hormodendrum compactum). In addition, compounds 1-7 showed a promising α-glycosidase inhibitory activity with IC50 values of 1.47, 1.55, 1.83, 2.76, 2.88, 3.16, and 2.94 mM, respectively, as compared with a positive control of acarbose (IC50 = 1.22 mM).