RESUMO
Twelve previously undescribed ophiobolin-type sesterterpenoids, undobolins A-L (1-12), were isolated from Aspergillus undulatus, and their structures were elucidated by spectroscopic analysis, ECD calculations, and single-crystal X-ray diffraction experiments. Compound 1 was the second example of 20-nor-ophiobolin reported, while compounds 2-6 were notable for oxygenation of C-2, and compound 6 showed significant inhibitory activity against ConA-induced T lymphocyte proliferation with an IC50 value of 2.3 µM, which suggests a promising new direction in the quest for immunosuppressive agents.
Assuntos
Aspergillus , Sesterterpenos , Sesterterpenos/farmacologia , Sesterterpenos/química , Sesterterpenos/isolamento & purificação , Aspergillus/química , Estrutura Molecular , Animais , Linfócitos T/efeitos dos fármacos , Cristalografia por Raios X , Imunossupressores/farmacologia , Imunossupressores/química , Imunossupressores/isolamento & purificação , Camundongos , Proliferação de Células/efeitos dos fármacosRESUMO
Five undescribed leucosesterterpane sesterterpenoids, leucosceptrines A-E, two undescribed penta-nor-leucosesterterpane (C20) sesterterpenoids, nor-leucosceptrines A and B, and three known analogues, were obtained from the aerial parts of Leucosceptrum canum of Chinese origin. Leucosceptrines A-C are the first examples of leucosesterterpane-type sesterterpenoids with unclosed dihydropyran rings and reverse configurations at chiral centers C-4 and/or C-12. Nor-leucosceptrines A and B possesses an unusual penta-nor-leucosesterterpane skeleton. Their structures were unambiguously elucidated through comprehensive spectroscopic analyses and single-crystal X-ray diffraction. A plausible biogenetic pathway for these sesterterpenoids was proposed. The immunosuppressive effects of these isolates on the secretion of the cytokine IFN-γ by T cells stimulated with anti-CD3/CD28 monoclonal antibodies were observed with different potencies.
Assuntos
Imunossupressores , Sesterterpenos , Sesterterpenos/química , Sesterterpenos/farmacologia , Sesterterpenos/isolamento & purificação , Imunossupressores/farmacologia , Imunossupressores/química , Imunossupressores/isolamento & purificação , Estrutura Molecular , Humanos , Linfócitos T/efeitos dos fármacos , Relação Estrutura-Atividade , Conformação Molecular , Interferon gamaRESUMO
Two new sesterterpenoids, atractylodes japonica terpenoid acid I (1) and atractylodes japonica terpenoid aldehyde I (2), were isolated from the rhizomes of Atractylodes japonica Koidz. ex Kitam together with ten known compounds (3-12). Their structures were elucidated on the basis of comprehensive spectroscopic analysis (1D/2D NMR, HRESIMS and IR). In addition, all of these isolated compounds were evaluated for their cytotoxic activities against human gastric cancer cell MGC-803 and human hepatocellular cancer cell HepG-2. Most of them exhibited moderate to weak inhibitory effects with IC50 values in the range of 25.15-88.85 µM except for 9-12.
Assuntos
Atractylodes , Rizoma , Sesterterpenos , Atractylodes/química , Humanos , Estrutura Molecular , Linhagem Celular Tumoral , Sesterterpenos/química , Sesterterpenos/farmacologia , Sesterterpenos/isolamento & purificação , Rizoma/química , Células Hep G2 , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Biofilm formation by Staphylococcus aureus plays a critical role in the persistence of chronic infections due to its tolerance against antimicrobial agents. Here, we investigated the antibiofilm efficacy of six phorbaketals: phorbaketal A (1), phorbaketal A acetate (2), phorbaketal B (3), phorbaketal B acetate (4), phorbaketal C (5), and phorbaketal C acetate (6), isolated from the Korean marine sponge Phorbas sp. Of these six compounds, 3 and 5 were found to be effective inhibitors of biofilm formation by two S. aureus strains, which included a methicillin-resistant S. aureus. In addition, 3 also inhibited the production of staphyloxanthin, which protects microbes from reactive oxygen species generated by neutrophils and macrophages. Transcriptional analyses showed that 3 and 5 inhibited the expression of the biofilm-related hemolysin gene hla and the nuclease gene nuc1.
Assuntos
Antibacterianos/farmacologia , Poríferos/química , Sesterterpenos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/isolamento & purificação , Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genes Bacterianos , Sesterterpenos/isolamento & purificação , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Staphylococcus aureus/fisiologia , Xantofilas/metabolismoRESUMO
Oshimalides A (1) and B (2) were isolated from a Luffariella sp. marine sponge. The absolute configurations of the stereogenic centers in the cyclohexenone ring were determined by the modified Mosher's analysis of the reduction product. The absolute configuration of the stereogenic center in the dihydropyran ring was assigned by analysis of the 1H NMR data of the vicinal diols which were prepared by AD-mix reagents stereoselectively.
Assuntos
Poríferos/química , Sesterterpenos/química , Animais , Organismos Aquáticos/química , Japão , Estrutura Molecular , Sesterterpenos/isolamento & purificação , TerpenosRESUMO
Dysiscalarones A-E (1-5), five new scalarane-type bishomoscalarane sesterterpenoids, were isolated from marine sponge Dysidea granulosa collected from the South China Sea, together with two known ones, honulactone A (6) and phyllofolactone I (7). The new structures were determined by extensive spectroscopic analysis including HR-ESI-MS and 1D and 2D NMR data, and their absolute configurations were assigned by single crystal X-ray diffraction analyses. The inhibitory activity of all the seven isolates on the production of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages was evaluated. Of these metabolites, dysiscalarones A-B (1-2), honulactone A (6), and phyllofolactone I (7) showed inhibitory activities with respective IC50 values of 16.4, 18.5, 2.6, and 3.7 µM, which suggested that the γ-methylated α,ß-unsaturated γ-lactone might be the functional group. In addition, all the seven metabolites showed no significant cytotoxicity against lung cancer PC9 cell line at the concentration of 20 µM.
Assuntos
Dysidea/química , Óxido Nítrico/antagonistas & inibidores , Sesterterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Células RAW 264.7 , Sesterterpenos/química , Sesterterpenos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Eurysoloids A (1) and B (2), two novel diastereomeric sesterterpenoids possessing a pentacyclic 5/6/5/10/5 framework with an unusual macrocyclic ether system, were isolated from Eurysolen gracilis Prain. Their structures were unambiguously determined by spectroscopic, single-crystal X-ray diffraction and DP4+ analyses. A plausible biosynthetic pathway for compounds 1 and 2 was proposed. Both compounds exhibited immunosuppressive activity via inhibiting the production of cytokine IFN-γ of T cells, and compound 2 inhibited adipogenesis in 3T3-L1 adipocytes.
Assuntos
Adipócitos/química , Adipogenia/efeitos dos fármacos , Éter/metabolismo , Lamiaceae/química , Sesterterpenos/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Éter/química , Camundongos , Estrutura Molecular , Sesterterpenos/química , Sesterterpenos/isolamento & purificaçãoRESUMO
Thirteen new linear terpenes, including 11 rare acyclic manoalide derivatives (1-11), one polyprenylphenol derivative (12), and one polyprenylbenzaldehyde derivative (13), together with three known compounds (14-16) were isolated from the sponge Luffariella variabilis collected in the South China Sea. The planar structures were resolved by NMR and MS analyses, while the absolute configurations were fully elucidated by NOESY experiments, combined with experimental and calculated ECD spectra, acetal formation, empirical rules of 1H and 13C NMR shifts, DP4+ probability analyses, and Mosher's method. Compounds 1-7, 10, and 13 demonstrated cytotoxic activities against several human cancer cell lines with IC50 values ranging from 2 to 10 µM.
Assuntos
Antineoplásicos/farmacologia , Poríferos/química , Sesterterpenos/farmacologia , Terpenos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular , China , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Sesterterpenos/química , Sesterterpenos/isolamento & purificação , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Lychnophora trichocarpha and Lychnophora passerina are species used in folk medicine to treat inflammation, pain, and rheumatism. Previous studies have demonstrated the anti-inflammatory effect of ethanol extracts of these species and identified that sesquiterpene lactones contribute to this activity. AIM OF THE STUDY: Gout is an acute inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints. Inflammation in joints induces oxidative stress in defense cells, releasing pro-inflammatory mediators. This study has three objectives: (1) to demonstrate the effects of sesquiterpene lactones lychnopholide and eremantholide C isolated from L. trichocarpha and goyazensolide isolated from L. passerina on arthritis induced by MSU crystals in C57BL6 mice; (2) to determine whether or not these compounds can inhibit the migration of neutrophils and the release of TNF-α and IL-1ß cytokines in the inflammation region; and (3) to evaluate the effects of sesquiterpene lactones on the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the cartilage of C57BL/6 mice with gouty arthritis. MATERIALS AND METHODS: The anti-inflammatory, antinociceptive, and antioxidant activities of sesquiterpene lactones in C57BL/6 mice with MSU crystal-induced arthritis were evaluated. In our experimental model, the mice were injected with MSU crystals in the tibiofemoral joint to induce arthritis and then treated with indomethacin, vitamin C, and sesquiterpene lactones. Nociception was evaluated before and after inflammation induction and treatments, neutrophil migration, IL-1ß and TNF-α concentrations, and SOD and CAT activities. RESULTS: Sesquiterpene lactones exerted an anti-inflammatory effect by inhibiting neutrophil migration and TNF-α production. These compounds also demonstrated antinociceptive and antioxidant activities. CONCLUSION: Lychnopholide, eremantholide C, and goyazensolide improved the inflammation induced by MSU crystals by inhibiting the migration of neutrophils to the inflamed area and by blocking the release of the pro-inflammatory cytokine TNF-α. In addition, sesquiterpene lactones reduced oxidative stress by activating SOD and CAT. These results suggest that sesquiterpene lactones have anti-gout activity through the inflammation, pain, and oxidative stress pathways.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Artrite Gotosa/tratamento farmacológico , Asteraceae/química , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Artrite Gotosa/induzido quimicamente , Hidrocarbonetos Aromáticos com Pontes/isolamento & purificação , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Catalase/metabolismo , Furanos/isolamento & purificação , Furanos/farmacologia , Furanos/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Articulações/efeitos dos fármacos , Lactonas/isolamento & purificação , Lactonas/uso terapêutico , Masculino , Medicina Tradicional/métodos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/uso terapêutico , Sesterterpenos/isolamento & purificação , Sesterterpenos/farmacologia , Sesterterpenos/uso terapêutico , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ácido Úrico/toxicidadeRESUMO
Three new ophiobolin sesterterpenoids, (6R)-16,17,21,21-O-tetrahydroophiobolin G (1), (6R)-16,17-dihydroophiobolin H (2), and (5S,6S)-16,17-dihydroophiobolin H (3), and three new farnesylated phthalide derivatives farnesylemefuranones D-F (9-11), along with five known ophiobolin analogues (4-8), were isolated and identified from the culture extract of Aspergillus insuetus SD-512, a deep-sea-derived fungus obtained from cold seep sediments collected at a depth of 1331 m. Among them, compounds 9-11 are rare examples of phthalide derivatives linked with farnesyl moieties via ether bonds. Their structures were established on the basis of detailed interpretation of the NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis, ECD calculations, and DP4+ probability analysis were performed to confirm the structures and establish the relative and absolute configurations of compounds 1-4. Compounds 3 and 9-11 showed broad-spectrum antibacterial activities, and differences in potencies could be assigned to structural modifications. This is the first report of secondary metabolites obtained from a deep sea cold-seep-derived fungus.
Assuntos
Aspergillus/química , Benzofuranos/isolamento & purificação , Sesterterpenos/isolamento & purificação , Benzofuranos/química , Temperatura Baixa , Oceanos e Mares , Prenilação , Sesterterpenos/química , Análise Espectral/métodosRESUMO
Deep-sea fungi have become a new arsenal for the discovery of leading compounds. Here five new ophiobolins 1-5, together with six known analogues 6-11, obtained from a deep-sea derived fungus WHU0154. Their structures were determined by analyses of IR, HR-ESI-MS, and NMR spectra, along with experimental and calculated electronic circular dichroism (ECD) analysis. Pharmacological studies showed that compounds 4 and 6 exhibited obvious inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine macrophage RAW264.7 cells. Mechanical study revealed that compound 6 could inhibit the inducible nitric oxide synthase (iNOS) level in LPS-stimulated RAW264.7 cells. In addition, compounds 6, 9, and 10 could significantly inhibit the expression of cyclooxygenase 2 (COX 2) in LPS-induced RAW264.7 cells. Preliminary structure-activity relationship (SAR) analyses revealed that the aldehyde group at C-21 and the α, ß-unsaturated ketone functionality at A ring in ophiobolins were vital for their anti-inflammatory effects. Together, the results demonstrated that ophiobolins, especially for compound 6, exhibited strong anti-inflammatory effects and shed light on the discovery of ophiobolins as new anti-inflammatory agents.
Assuntos
Anti-Inflamatórios/farmacologia , Aspergillus/metabolismo , Macrófagos/efeitos dos fármacos , Sesterterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Ciclo-Oxigenase 2/metabolismo , Sedimentos Geológicos/microbiologia , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Metabolismo Secundário , Sesterterpenos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Two new bioactive ophiobolan sestertepenoids, named drophiobiolins A and B (1 and 2) were isolated from Drechslera gigantea, a fungus proposed as a mycoherbicide for biocontrol of Digitaria sanguinalis. They were isolated together with ophiobolin A, the main metabolite, 6-epi-ophiobolin A, 3-anhydro-6-epi-ophiobolin A, and ophiobolin I. Drophiobolins A and B were characterized by NMR, HRESIMS, and chemical methods as 7-hydroxy-7-(6-hydroxy-6-methylheptan-2-yl)-1,9a-dimethyl-3-oxo-3,3a,6,6a,7,8,9,9a,10,10a-decahydrodicyclopenta [a,d][8]annulene-4-carbaldehyde and 6-(hydroxymethyl)-3',9,10a-trimethyl-5'-(2-methylprop-1-en-1-yl)-3a,4,4',5',10,10a-hexahydro-1H,3'H-spiro[dicyclopenta[a,d] [8]annulene-3,2'-furan]-5,7(2H,9aH)-dione. The relative configuration of drophiobolins A and B, which did not afford crystals suitable for X-ray analysis, was determined by NOESY experiments, while the absolute configuration was assigned by comparison of their experimental and TDDFT calculated electronic circular dichroism (ECD) spectra. The phytotoxic activity of drophiobolins A and B was tested by leaf-puncture assay on cultivated (Lycopersicon esculentum L.), as well as on host (Digitaria sanguinalis L.) and nonhost (Chenopodium album L.) weed plants, compared to that of ophiobolin A. Both of the newly identified ophiobolins showed significant phytotoxicity. Drophiobolins A and B exhibited cytotoxicity against Hela B cells with an IC50 value of 10 µM. However, they had a lesser or no effect against Hacat, H1299, and A431 cells when compared to that of ophiobolin A.
Assuntos
Ascomicetos/química , Sesterterpenos/isolamento & purificação , Linhagem Celular , Cristalografia por Raios X , Humanos , Sesterterpenos/química , Sesterterpenos/farmacologia , Análise Espectral/métodos , Relação Estrutura-AtividadeRESUMO
Chemical investigation on a marine sponge, Dactylospongia elegans, yielded five new γ-oxygenated butenolide sesterterpene derivatives, dactylospenes A-E (1-5), as well as two known biosynthetically related compounds, luffariellolide (6) and furospinosulin B (7). The structures of these compounds were elucidated on the basis of their spectroscopic data, experimental and calculated electronic circular dichroism (ECD) analysis, as well as comparison of the NMR data with those of known analogs. These metabolites are the first γ-oxygenated butenolide sesterterpenes to be reported from this genus. These compounds were evaluated in antimicrobial, anti-inflammatory, and cytotoxic assays. Only compounds 1, 3, and 6 exhibited moderate cytotoxicity against DU145, SW1990, Huh7, and PANC-1 cancer cell lines with IC50 values in the range of 2.11-13.35 µM. Furthermore, compound 2, without cytotoxicity, exhibited significant inhibitory effects (inhibitory rate 77.5%) on nitric oxide production induced by lipopolysaccharide at 10 µM.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Antineoplásicos/isolamento & purificação , Poríferos/metabolismo , Sesterterpenos/isolamento & purificação , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Lipopolissacarídeos , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7 , Sesterterpenos/química , Sesterterpenos/farmacologia , Terpenos/isolamento & purificaçãoRESUMO
The biosynthetic gene cluster for the sesterterpenoids asperterpenols A and B from Aspergillus calidoustus CBS121601 is described. The cluster contains two genes, acldAS for a chimeric sesterterpene synthase and acldA-P450 for a cytochrome P450 monooxygenase. The cyclization mechanism of the asperterpenol A synthase, catalyzing the formation of a unique sesterterpene with a 6/6/8/5 tetracyclic ring system, was studied using isotopically labeled terpene precursors.
Assuntos
Alquil e Aril Transferases/química , Aspergillus/química , Sesterterpenos/farmacologia , Catálise , Estrutura Molecular , Família Multigênica , Sesterterpenos/química , Sesterterpenos/isolamento & purificação , Sesterterpenos/metabolismoRESUMO
Scalarane-type sesterterpenoids are known for their therapeutic potential in cancer treatments. However, the anti-inflammatory properties of this class of metabolites remain elusive. Our current work aimed to investigate the anti-inflammatory scalaranes from marine sponge Lendenfeldia sp., resulting in the isolation of six new 24-homoscalaranes, lendenfeldaranes E-J (1-6). The structures of the new metabolites were determined by extensive spectroscopic analyses, and the absolute configuration of 1 was established by electronic circular dichroism (ECD) calculations. Compounds 2 and 3 were discovered to individually reduce the generation of superoxide anions, and compound 1 displayed an inhibitor effect on the release of elastase. These three compounds were proven to be the first anti-neutrophilic scalaranes.
Assuntos
Anti-Inflamatórios/farmacologia , Neutrófilos/efeitos dos fármacos , Poríferos/química , Sesterterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Humanos , Elastase de Leucócito/metabolismo , Estrutura Molecular , Neutrófilos/metabolismo , Via Secretória , Sesterterpenos/química , Sesterterpenos/isolamento & purificação , Relação Estrutura-Atividade , Superóxidos/metabolismoRESUMO
A meroterpenoid, guanahanolide A (1), was purified from a fermentation extract of Streptomyces sp. RKBH-B7. The planar structure of guanahanolide A (1) was elucidated by NMR spectroscopy, revealing a meroterpenoid comprised of an unprecedented sesterterpene skeleton. Upon determination of the relative configuration of 1 through X-ray crystallography, its absolute configuration was unambiguously assigned using Mosher ester analysis. Guanahanolide A (1) showed moderate cytotoxicity against human cancer cell lines MCF-7, HTB-26, and HCT-116.
Assuntos
Antineoplásicos/farmacologia , Sesterterpenos/farmacologia , Streptomyces/química , Animais , Antozoários , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Cristalografia por Raios X , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Sesterterpenos/química , Sesterterpenos/isolamento & purificaçãoRESUMO
12-Deacetyl-12-epi-scalaradial, a scalarane sesterterpenoid from a marine sponge Hippospongia sp, has been reported to possess cytotoxic activity on HepG2, MCF-7, and HCT-116 cells. However, there is no research to indicate that 12-deacetyl-12-epi-scalaradial exhibited anticancer effect on cervical cancer HeLa cells. The aim of this study was to investigate the anticancer activity of 12-deacetyl-12-epi-scalaradial against HeLa cells and to explore the mechanism. The results from a methylthiazolyldiphenyl-tetrazolium (MTT) assay suggested that 12-deacetyl-12-epi-scalaradial suppressed the proliferation of HeLa cells and flow cytometry analysis showed 12-deacetyl-12-epi-scalaradial could induce the apoptosis of HeLa cells in dose- and time-dependent manner. Western blotting analysis demonstrated that 12-deacetyl-12-epi-scalaradial triggered apoptosis via mediating the extrinsic pathway and was found to suppress MAPK/ERK pathway which was associate with cancer cell death. Nur77, a critical number of orphan nuclear receptors, plays diverse roles in tumor development as a transcription factor and has been considered as a promising anticancer drug target. The dual-luciferase reporter assays suggested that 12-deacetyl-12-epi-scalaradial could selectively enhance the trans-activation activity of Nur77. Furthermore, Western blotting analysis and fluorescence quenching showed that 12-deacetyl-12-epi-scalaradial could induce the phosphorylation of Nur77 and interact with the ligand-binding domain (LBD) of Nur77. Our research confirmed 12-deacetyl-12-epi-scalaradial as a potential agent for cervical cancer therapy and provided a view that 12-deacetyl-12-epi-scalaradial may be a modulator of Nur77.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Poríferos/química , Sesterterpenos/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/isolamento & purificação , Proteínas Reguladoras de Apoptose/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Fosforilação , Sesterterpenos/isolamento & purificação , Transdução de Sinais , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologiaRESUMO
Five sesterterpenes (1-5) including two new compounds (1 and 2), as well as a new (6) and a known macrolide (7) were isolated from the endophytic fungus Aplosporella javeedii. The structures of the new compounds were elucidated by analysis of their 1D and 2D NMR and HRMS data as well as by comparison with the literature. Compound 4 and its acetyl derivatives 4a, 4b, 4c which were prepared by acetylation of 4 exhibited moderate cytotoxicity against the mouse lymphoma cell line L5178Y with IC50 values ranging from 6.2 to 12.8 µM, respectively. Moreover, 4a and 4c exhibited also cytotoxicity against human leukemia (Jurkat J16) and lymphoma (Ramos) cell lines. Compound 7 showed strong cytotoxicity against the L5178Y cell line, as well as against human Jurkat J16 and Ramos cells with IC50 values of 0.4, 5.8, and 4.4 µM, respectively. Mechanistic studies indicated that 7 induces apoptotic cell death. In addition, compounds 3, 4 and 7 showed low antibacterial activities against Mycobacterium tuberculosis H37Rv and compound 6 against Staphylococcus aureus, respectively, with MICs of 100 µM. Preliminary structure-activity relationships are discussed.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Ascomicetos/química , Macrolídeos/farmacologia , Sesterterpenos/farmacologia , Animais , Antibacterianos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Brassicaceae/microbiologia , Linhagem Celular Tumoral , China , Endófitos/química , Humanos , Macrolídeos/isolamento & purificação , Camundongos , Estrutura Molecular , Sesterterpenos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Granulosane A (1), a new C27 bishomoscalarane sesterterpenoid with a rare 6/6/6/8 tetracyclic skeleton, together with eight additional new C27 bishomoscalarane sesterterpenes (2, 8-14) and five new C26 20,24-bishomo-25-norscalarane sesterterpenes (3-7), were isolated from the marine sponge Dysidea granulosa collected in the South China Sea. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculation methods. Compound 4 showed antiproliferative activities against two cancer cell lines.
Assuntos
Antineoplásicos/isolamento & purificação , Dysidea/química , Sesterterpenos/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , China , Humanos , Estrutura Molecular , Polissacarídeos/química , Poríferos/química , Sesterterpenos/química , Sesterterpenos/farmacologiaRESUMO
In the current study, an NMR spectroscopic pattern-based procedure for probing scalarane derivatives was performed and four new 24-homoscalaranes, lendenfeldaranes A-D (1- 4), along with three known compounds, 12α-acetoxy-22-hydroxy-24-methyl-24-oxoscalar-16-en- 25-al (5), felixin F (6), and 24-methyl-12,24,25-trioxoscalar-16-en-22-oic acid (7) were isolated from the sponge Lendenfeldia sp. The structures of scalaranes 1-7 were elucidated on the basis of spectroscopic analysis. Scalaranes 1-7 were further evaluated for their cytotoxicity toward a series of human cancer cell lines and the results suggested that 5 and 7 dominated in the anti- proliferative activity of the extract. The 18-aldehyde functionality was found to play a key role in their activity.