RESUMO
Six new 2α-hydroxy ursane triterpenoids, 3α-cis-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (1), 3α-trans-p-coumaroyloxy-2α,19α-dihydroxy-12-ursen-28-oic acid (2), 3α-trans-p-coumaroyloxy-2α-hydroxy-12-ursen-28-oic acid (3), 3ß-trans-p-coumaroyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (4), 3ß-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (5), and 3α-trans-feruloyloxy-2α-hydroxy-12,20(30)-ursadien-28-oic acid (6), along with eleven known triterpenoids (7-17), were isolated from the leaves of Diospyros digyna. Their chemical structures were elucidated by comprehensive analysis of UV, IR, HRESIMS, and NMR spectra. All the isolated compounds were evaluated for their PTP1B inhibitory activity. 3ß-O-trans-feruloyl-2α-hydroxy-urs-12-en-28-oic acid (13) showed the best inhibition activity with an IC50 value of 10.32 ± 1.21 µM. The molecular docking study found that the binding affinity of compound 13 for PTP1B was comparable to that of oleanolic acid (positive control).
Assuntos
Diospyros , Triterpenos , Simulação de Acoplamento Molecular , Folhas de Planta , Hidroxiácidos , Triterpenos/farmacologiaRESUMO
In this study, an extract of the leaves of Eremophila clarkei Oldfield & F.Muell. showed protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with an IC50 value of 33.0 µg/mL. The extract was therefore investigated by high-resolution PTP1B inhibition profiling to pinpoint the constituents responsible for the activity. Subsequent isolation and purification using analytical-scale HPLC led to identification of eight previously undescribed decipiene diterpenoids, eremoclarkanes A-H, as well as eremoclarkic acid, a biogenetically related new phenolic acid. In addition, one known decipiene diterpenoid and ten known O-methylated flavonoids were isolated. The structures of the isolated compounds were elucidated by extensive analysis of their HRMS and 1D and 2D NMR spectra. The absolute configuration of decipiene diterpenoids was determined by comparison of experimental and calculated ECD spectra. The flavonoid hispidulin (2b) and the four decipiene diterpenoids 13a, 13b, 13f, and 14b exhibited PTP1B inhibitory activity with IC50 values ranging from 22.8 to 33.6 µM. This is the first report of PTP1B inhibitory activity of decipienes, and enzyme kinetics revealed that 13a and 13b are competitive inhibitors of PTP1B, whereas 13f and 14b displayed mixed-type-mode inhibition of PTP1B. Finally, molecular docking indicated that 13a, 13b, 13f, and 14b showed comparable binding affinity towards the active and/or allosteric site of PTP1B enzyme. Structure-activity relationship (SAR) of the identified O-methylated flavonoids and decipiene diterpenoids towards PTP1B is discussed. Plausible enzymatic and photochemically driven routes for the formation of the decipienes and conversion products thereof are presented and discussed.
Assuntos
Diterpenos , Extratos Vegetais , Simulação de Acoplamento Molecular , Cinética , Extratos Vegetais/química , Flavonoides , Diterpenos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Inibidores Enzimáticos/químicaRESUMO
Two new polyketides, palitantins B and C (1 and 2), along with one known related compound (+)-palitantin (3) were obtained from the culture of the Antarctic fungus Geomyces sp. 3-1. The structures of the new compounds were elucidated by detailed analysis of HRESIMS, NMR, CD, and ECD data. Compound 3 showed potent PTP1B inhibitory activity with an IC50 value of 7.9 µM (ursolic acid as positive control, IC50 = 8.3 µM).
Assuntos
Ascomicetos , Policetídeos , Cicloexanóis , Cicloexanonas , Estrutura Molecular , Policetídeos/farmacologiaRESUMO
Nine undescribed monoterpene phenol dimers, bisbakuchiols D-L (1-9), were isolated from the fruits of Psoralea corylifolia L. Their structures were elucidated based on extensive spectral analysis. The absolute configurations of 1-9 were specified by experimental and quantum chemical calculations of ECD spectra, and that of 1 was further established by X-ray diffraction analysis using Cu Kα radiation. Bisbakuchiols (1-4) were composed of two bakuchiols, one of which was cyclized via a C-7'/ C-12' single bond to form a six-member ring, and connect to each other by C-4-O-C-13' bonds. Bisbakuchiols (7-9) had a pyran ring by linkage of C-8-O-C-12. In the enzyme assay, compounds 5 and 9 exhibited significant PTP1B inhibitory activities with IC50 values of 0.69 and 0.73 µM, and compounds 1 and 3 showed moderate PTP1B inhibitory activities. Furthermore, a molecular docking simulation of PTP1B and active compounds 5 and 9 showed that these active compounds possess low binding affinities ranging from -6.9 to -7.1 kcal/mol.
Assuntos
Inibidores Enzimáticos/farmacologia , Frutas/química , Monoterpenos/farmacologia , Fenóis/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Psoralea/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Monoterpenos/química , Monoterpenos/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-AtividadeRESUMO
The phytochemical investigation on the fruits of Clausena anisum-olens led to the isolation of 18 carbazole alkaloids (1-18), containing three new ones, clausenanisines A-C (1-3), and three new naturally occurring carbazole alkaloids, clausenanisines D-F (4-6), as well as 12 known analogues (7-18). The chemical structures of clausenanisines A-F (1-6) were elucidated by extensive spectroscopic methods. Notably, clausenanisine A (1) was a novel carbazole alkaloid with a unique five-membered cyclic ether, while clausenanisine E (5) is an unusual carbazole alkaloid owning an unprecedented naturally occurring carbon skeleton possessing 14 carbon atoms. The known carbazole alkaloids (7-18) were identified by the comparison of their spectral data with those data reported in the literature. All known carbazole alkaloids 7-18 were isolated from C. anisum-olens for the first time. Moreover, all isolated compounds 1-18 were assessed for their protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities in vitro. Compounds 1-18 exhibited remarkable PTP1B inhibitory activities with IC50 values in the range of 0.58 ± 0.05 to 38.48 ± 0.32 µM, meanwhile, compounds 1-18 displayed significant α-glucosidase inhibitory activities with IC50 values ranging from 3.28 ± 0.16 to 192.23 ± 0.78 µM. These research results imply that the separation and identification of these carbazole alkaloids showing notable PTP1B and α-glucosidase inhibitory activities from the fruits of C. anisum-olens can be very significant for discovering and developing new PTP1B inhibitors and α-glucosidase inhibitors for the treatment of diabetes mellitus.
Assuntos
Alcaloides/farmacologia , Carbazóis/farmacologia , Clausena/química , Inibidores Enzimáticos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Alcaloides/química , Alcaloides/isolamento & purificação , Carbazóis/química , Carbazóis/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Frutas/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-AtividadeRESUMO
Six undescribed polyhydroxy p-terphenyls, namely asperterphenyllins A-F, were isolated from an endophytic fungus Aspergillus candidus LDJ-5. Their structures were determined by NMR and MS data. Differing from the previously reported p-terphenyls, asperterphenyllin A represents the first p-terphenyl dimer connected by a C-C bond. Asperterphenyllin A displayed anti-influenza virus A (H1N1) activity and protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with IC50 values of 53 µM and 21 µM, respectively. The anti-influenza virus A (H1N1) activity and protein tyrosine phosphatase 1B (PTP1B) inhibitory activity of p-terphenyls are reported for the first time. Asperterphenyllin G exhibited cytotoxicity against nine cell lines with IC50 values ranging from 0.4 to 1.7 µM. Asperterphenyllin C showed antimicrobial activity against Proteus species with a MIC value of 19 µg/mL.
Assuntos
Aspergillus/efeitos dos fármacos , Endófitos/efeitos dos fármacos , Rhizophoraceae , Compostos de Terfenil/isolamento & purificação , Compostos de Terfenil/farmacologia , Aspergillus/fisiologia , Endófitos/fisiologia , Células HCT116 , Células HL-60 , Células HeLa , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/fisiologia , Células K562 , Células MCF-7 , Compostos de Terfenil/químicaRESUMO
The barks of Magnolia officinalis var. biloba, Magnoliae cortex, have been used as traditional Chinese medicines for several centuries. In this study, phytochemical investigation of M. officinalis var. biloba bark extract afforded five pairs of novel enantiomeric oligomeric neolignans, (±)-mooligomers A-E (1-5). (±)-1 and (±)-2 were two diastereomeric pairs of enantiomers with six C6-C3 subunits, and (±)-4 was a pair of previously unreported tetrameric neolignans bearing eight C6-C3 subunits. (±)-5 is the first example of a naturally occurring trilignan featuring an eight-membered ring with a magnolol moiety. The absolute configurations of (±)-1-(±)-5 were elucidated on the basis of HRESIMS, 1D and 2D NMR spectroscopy and electronic circular dichroism (ECD) calculations. Among the compounds tested for their PTP1B inhibitory activities, (±)-2, (±)-4 and (±)-5 displayed significant PTP1B inhibitory activities with IC50 values of 0.14-2.10 µM. Furthermore, a Molecular docking simulation of PTP1B and active compounds [(±)-2, (±)-4 and (±)-5] exhibited that these active compounds possess low binding affinities ranging from - 5.9 to - 7.7 kcal/mol.
Assuntos
Inibidores Enzimáticos/farmacologia , Lignanas/farmacologia , Magnolia/química , Casca de Planta/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-AtividadeRESUMO
Seven flavonoid dimers, biflavocochins A-G, together with six known compounds were isolated from the red resins of Dracaena cochinchinensis (Chinese dragon's blood). Their structures were elucidated based on extensive spectroscopic analysis. The absolute configurations of 1-7 was assigned by experimental and quantum chemical calculated ECD spectra, and that of 4 was further established by X-ray diffraction analysis using Cu Kα radiation. Compounds 1-3 are novel dimers of homoisoflavonoid and dihydrochalcone with a unique dibenzopyran ring. Compounds 2, 6, 7 exhibited moderate PTP1B inhibitory activities in an enzyme assay. Compound 1 showed neuroprotective effect on serum deficiency-induced cellular damage in PC12 cells.
Assuntos
Dracaena/química , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Animais , Cristalografia por Raios X , Dimerização , Inibidores Enzimáticos/química , Flavonoides/química , Humanos , Modelos Moleculares , Fármacos Neuroprotetores/química , Células PC12 , Extratos Vegetais/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , RatosRESUMO
In the course of studying the components from the roots of Sophora flavescens, eight new unusual biflavonoids consisting of a flavanone fused with a dihydrochalcone skeleton were isolated. These new chemical structures were elucidated by means of UV, IR, HRESIMS, NMR and ECD spectroscopic data and a comparison of experimental ECD spectra with calculated ECD spectra. Some compounds were subjected to an antidiabetic bioassay on human recombinant PTP1B inhibition, and showed strong inhibitory activity.
Assuntos
Monoterpenos Acíclicos/farmacologia , Biflavonoides/farmacologia , Inibidores Enzimáticos/farmacologia , Extratos Vegetais/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Sophora/química , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/isolamento & purificação , Biflavonoides/química , Biflavonoides/isolamento & purificação , Chalconas/química , Chalconas/isolamento & purificação , Chalconas/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteínas Recombinantes/metabolismo , Relação Estrutura-AtividadeRESUMO
Eight new meroterpenoids with different types of monoterpene units, namely, magmenthanes A-H (1-8), were identified from the bark of Magnolia officinalis var. biloba. Magmenthane A (1) possesses a 1,3-dioxabicyclo [4.3.01,5] nonane skeleton, 1-5 possess five pairs of enantiomers and 6 possesses a 1,1'-diallyl-biphenyl fragment. The structures of 1-8 were elucidated on the basis of 1D and 2D NMR, HRESIMS and electronic circular dichroism (ECD) calculations. Compounds 5 and 8 displayed significant PTP1B inhibitory activities with IC50 values of 4.38 and 3.88⯵M, respectively.
Assuntos
Inibidores Enzimáticos/farmacologia , Magnolia/química , Fármacos Neuroprotetores/farmacologia , Casca de Planta/química , Extratos Vegetais/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Terpenos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Ácido Glutâmico/farmacologia , Humanos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
A new prenyleudesmane type diterpene, sinupol (8), and a new capnosane type diterpenoid, sinulacetate (9), were isolated from the Xisha soft coral Sinularia polydactyla along with five known related diterpenes (4-7 and 10). Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, the comparison of their NMR data with those of related compounds, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Both new compounds (8 and 9) exhibited promising inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a potential drug target for the treatment of type II diabetes and obesity.
Assuntos
Antozoários/química , Diterpenos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Animais , Diterpenos/química , Modelos Moleculares , Estrutura MolecularRESUMO
Acorn leaves, which possess potential pharmacologic effects, are traditionally consumed as food in China. Phytochemical investigations of acorn leaves yielded one new and 25 known polyphenols, and their structures were identified by extensive spectroscopic analysis. Three antidiabetes assays were conducted. Compound 2 considerably increased the survival of pancreatic beta cells by reducing the production of reactive oxygen species and enhancing the activities of superoxide dismutase, catalase, and glutathione in MIN6 cells damaged by H2O2. The preliminary mechanism by which compound 2 protects pancreatic beta cells was through the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 HO-1 pathway. Most of the tested isolates showed strong inhibitory activity against α-glucosidase and protein tyrosine phosphatase 1B. The IC50 values of most compounds were much lower than those of the positive control. The results suggest that polyphenols from acorn leaves are potential functional food ingredients that can be used as antidiabetic agents.
Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Quercus/química , Antioxidantes/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Heme Oxigenase-1/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , alfa-GlucosidasesRESUMO
Minor metabolic components, six new cembranoids sarcophytrols G - L (1 - 6) along with two known related analogues 7 and 8, were isolated from the South China Sea soft coral Sarcophyton trocheliophorum. Their structures were elucidated by extensive spectroscopic analyses (1D-, 2D-NMR, and ESI-MS) as well as comparison with literature data. As part of our ongoing research project for discovering bioactive substances from Chinese marine invertebrates, compounds 1 - 8 were tested for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of Type-II diabetes and obesity. However, none of them exhibited potent PTP1B inhibitory activities.
Assuntos
Antozoários/metabolismo , Antineoplásicos/isolamento & purificação , Diterpenos/isolamento & purificação , Animais , Antozoários/química , Antineoplásicos/química , China , Diterpenos/química , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Análise EspectralRESUMO
The present study was designed to develop a concise synthetic route for macrolide, with the purpose of confirming the absolute configuration of natural dihydroresorcylide (1) and making it more easily accessible for biological evaluation. The absolute configuration of C-3 in natural 1 was revised to be R by comparison of the rotation sign of synthetic (R)- and (S)-1. The synthetic (R)-1 was found to be a novel highly specific PTP1B inhibitor with an IC50 value of 17.06 µM.
Assuntos
Macrolídeos/síntese química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Desenho de Fármacos , Macrolídeos/química , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
A new steroidal ketone (1), with an ergosta-22,25-diene side chain, was obtained from the South China Sea marine sponge Xestospongia testudinaria. The structure of 1 was determined on the basis of detailed spectroscopic analysis and by comparison with literature. Compound 1 exhibited significant inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of type II diabetes and obesity, with an IC50 value of 4.27 ± 0.55 µM, which is comparable with the positive control oleanolic acid (IC50 = 2.63 ± 0.22 µM).
Assuntos
Colestanóis/isolamento & purificação , Colestanóis/farmacologia , Xestospongia/química , Animais , Colestanóis/química , Diabetes Mellitus Tipo 2 , Cetonas , Estrutura Molecular , Oceanos e Mares , Ácido Oleanólico , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , EsteroidesRESUMO
Three diterpenoids, including a pair of epimers, racemobutenolids A and B (1 and 2), and 4',5'-dehydrodiodictyonema A (3), an α-tocopheroid, α-tocoxylenoxy (8), and an 28-oxostigmastane steroid, (23E)-3ß-hydroxy-stigmasta-5,23-dien-28-one (11), together with 12 known compounds, were isolated from the green alga Caulerpa racemosa. The structures of the new compounds were elucidated by detailed analysis of spectroscopic data, and by comparison with data for related known compounds. The epimers (1 and 2) are two unusual diterpenoid lactones bearing a ß-methyl-γ-substituted butenolide moiety, and 3 and 8 represent the first naturally occurring natural products with a hematinic acid ester group and 3,5-dimethylphenoxy functionality, respectively. The enzyme inhibitory activities of the isolated compounds were evaluated in vitro against PTP1B and related PTPs (TCPTP, CDC25B, LAR, SHP-1, and SHP-2). Compounds 3, 5, 6, and 9-14 exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 2.30 to 50.02µM. Of these compounds, 3, 9, and 11 showed the most potent inhibitory activities towards PTP1B with IC50 values of 2.30, 3.85, and 3.80µM, respectively. More importantly, the potent PTP1B inhibitors 3, 9, and 11 also displayed high selectivity over the highly homologous TCPTP and other PTPs. Also, the neuroprotective effects of the isolates against Aß25-35-induced cell damage in SH-SY5Y cells were investigated. Compounds 10, 11, and 14 exhibited significant neuroprotective effects against Aß25-35-induced SH-SY5Y cell damage with 11.31-15.98% increases in cell viability at 10µM. In addition, the cytotoxic activities of the isolated compounds were tested against the human cancer cell lines A-549 and HL-60.
Assuntos
Caulerpa/química , Diterpenos/química , Diterpenos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Produtos Biológicos , Células HL-60 , Humanos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Relação Estrutura-AtividadeRESUMO
A new brominated polyunsaturated lipid, methyl (E,E)-14,14-dibromo-4,6,13-tetradecatrienoate (1), along with three known related analogues (2-4), were isolated from the Et2O-soluble portion of the acetone extract of Chinese marine sponge Xestospongia testudinaria treated with diazomethane. The structure of the new compound was elucidated by detailed spectroscopic analysis and by comparison with literature data. Compound 3 exhibited significant inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of type II diabetes and obesity, with an IC50 value of 5.30 ± 0.61 µM, when compared to the positive control oleanolic acid (IC50 = 2.39 ± 0.26 µM).
Assuntos
Ácidos Graxos Insaturados/isolamento & purificação , Ácidos Graxos Insaturados/farmacologia , Hidrocarbonetos Bromados/isolamento & purificação , Hidrocarbonetos Bromados/farmacologia , Poríferos/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Xestospongia/química , Animais , Diabetes Mellitus Tipo 2 , Ácidos Graxos Insaturados/química , Hidrocarbonetos Bromados/química , Biologia Marinha , Estrutura Molecular , Países Baixos , Ácido Oleanólico/químicaRESUMO
A novel minor bisindole alkaloid, racemosin C (1), characterized by a naturally unprecedented 8-hydroxy-2,4,6-cyclooctatrienone ring fused with two indole systems, was isolated from the green alga Caulerpa racemosa, together with one known related metabolite, caulersin (2). The structure of 1 was elucidated on the basis of extensive spectroscopic analysis, and by comparison with the data of related known compounds. A plausible biosynthetic pathway of 1 was proposed. Compounds 1 and 2 exhibited significant PTP1B inhibitory activity with IC50 values of 5.86 ± 0.57 and 7.14 ± 1.00 µM, respectively, compared with the positive control oleanolic acid (IC50 = 3.03 ± 0.20 µM). On the basis of the data obtained, the Caulerpa bisindole alkaloids may be considered as a new class of PTP1B inhibitors.
Assuntos
Caulerpa/química , Alcaloides Indólicos/isolamento & purificação , Alcaloides Indólicos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Alcaloides Indólicos/química , Isoquinolinas , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oceanos e Mares , Ácido Oleanólico/químicaRESUMO
Eleven oleanane triterpenoids (1-11) including two new ones (1 and 2) were isolated from the roots and stems of Caulophyllum robustum. Their structures were established by extensive spectroscopic analysis, comparison with literature, and NMR calculations. Compounds 1 and 2 represent the first examples of 23-hydroxy-28-nor-oleanane and 21-hydroxy-olean-3-one triterpenoids, respectively. All isolates were evaluated for their PTP1B and α-glucosidase inhibitory activities in vitro. Among them, the triterpene aglycones 1-5 showed almost equivalent PTP1B inhibitory activities to oleanolic acid and ursolic acid, while 1, 2, and the triterpene saponins 6-11 showed significant α-glucosidase inhibitory activities. Furthermore, compounds 1 and 3 were proved to regulate the expression of proteins implicated the PTP1B/IRS-1/pIRS-1 signalling pathway to improve insulin resistance.
RESUMO
Five novel (9,10-dihydro) phenanthrene and bibenzyl trimers, as well as two previously identified biphenanthrenes and bibenzyls, were isolated from the tubers of Bletilla striata. Their structures were elucidated through comprehensive analyses of NMR and HRESIMS spectroscopic data. The absolute configurations of these compounds were determined by calculating rotational energy barriers and comparison of experimental and calculated ECD curves. Compounds 5b and 6 exhibited inhibitory effects on LPS-induced NO production in BV-2 cells, with IC50 values of 12.59 ± 0.40 and 15.59 ± 0.83 µmol·L-1, respectively. A mechanistic study suggested that these compounds may attenuate neuroinflammation by reducing the activation of the AKT/IκB/NF-κB signaling pathway. Additionally, compounds 3a, 6, and 7 demonstrated significant PTP1B inhibitory activities, with IC50 values of 1.52 ± 0.34, 1.39 ± 0.11, and 1.78 ± 0.01 µmol·L-1, respectively. Further investigation revealed that compound 3a might inhibit LPS-induced PTP1B overexpression and NF-κB activation, thereby mitigating the neuroinflammatory response in BV-2 cells.