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INTRODUCTION: Kamebakaurin is an active constituent of both Rabdosia japonica and Rabdosia excisa, which are utilized in Chinese traditional medicine for improving symptoms in patients with allergies. We investigated the molecular mechanisms of the anti-allergic effects of kamebakaurin using BMMCs. METHODS: The degranulation ratio, histamine release, and the interleukin (IL)-4, leukotriene B4 (LTB4), and cysteinyl leukotriene productions on antigen-triggered BMMC were investigated. Additionally, the effects of kamebakaurin on signal transduction proteins were examined by Western blot and binding to the Syk and Lyn kinase domain was calculated. The effects of kamebakaurin on antigen-induced hyperpermeability were investigated using mouse model. RESULTS: At 10 µ
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Natural polybrominated diphenyl ethers are generally isolated from sponges and possess a broad range of biological activities. Through screening of our marine natural product library, we discovered that polybrominated diphenyl ethers 5 and 6 exhibit considerable anti-inflammatory activity. In order to expand our repertoire of derivatives for further biological activity studies, we designed and synthesized a series of 5-related polybrominated diphenyl ethers. Importantly, compound 5a showed comparable anti-inflammatory activity while much lower cytotoxicity on lipopolysaccharide (LPS)-induced RAW264.7 cells. Additionally, western blotting analysis showed that 5a reduced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK). Besides, molecular docking experiments were conducted to predict and elucidate the potential mechanisms underlying the varying anti-inflammatory activities exhibited by compounds 5a, 5, and 6.
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Hepatitis B Virus (HBV) infection is a global public health challenge that seriously endangers human health. Soft coral, as a major source of terpenoids, contains many structurally novel and highly bioactive compounds. Sixteen cembranoids (1-16), including a new one named sinupedunol B (16), were isolated from the South China Sea Soft coral Sinularia pedunculata. The structure of the sinupedunol B (16) was determined through a combination of spectroscopic analysis and X-ray single-crystal diffraction. In this study, cembranoids isolated from Sinularia pedunculata were found of anti-HBV activity for the first time. Among them, flexilarin D (6) showed significant anti-HBV activity with an IC50 value of 5.57â µM without cytotoxicity. We then analyzed the structure-activity relationship (SAR). Furthermore, it is demonstrated that flexilarin D (6) can accelerate the formation of capsid, inhibit HBeAg, HBV core particle DNA, HBV total RNA and pregenomic RNA in a dose dependent manner. We also confirmed the anti-HBV activity of 6 in HepG2-NTCP infection system. Finally, we demonstrated the anti-HBV mechanism of these compounds by inhibiting the ENI/Xp enhancer/promoter.
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Covering: 2011-2021Marine mollusks, which are well known as rich sources of diverse and biologically active natural products, have attracted significant attention from researchers due to their chemical and pharmacological properties. The occurrence of some of these marine mollusk-derived natural products in their preys, predators, and associated microorganisms has also gained interest in chemical ecology research. Based on previous reviews, herein, we present a comprehensive summary of the recent advances of interesting secondary metabolites from marine mollusks, focusing on their structural features, possible chemo-ecological significance, and promising biological activities, covering the literature from 2011 to 2021.
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Produtos Biológicos , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Moluscos/químicaRESUMO
A detailed chemical investigation of the Sanya Bay nudibranch Hexabranchus sanguineus yielded thirteen new sesquiterpenoids, namely sanyagunins A-H, sanyalides A-C, and sanyalactams A and B, along with eleven known related ones. Sanyalactams A and B feature an unprecedented hexahydrospiro[indene-2,3'-pyrrolidine] core. The structures of new compounds were established by a combination of extensive spectroscopic data analysis, quantum mechanical-nuclear magnetic resonance methods, the modified Mosher's method, and X-ray diffraction analysis. Based on analysis of NOESY correlations and the modified Mosher's method, the stereochemistry of two known furodysinane-type sesquiterpenoids were revised. A plausible biogenetic relationship between these sesquiterpenoids wasproposed and discussed, and a chemo-ecological relationship of the title animal and its possible sponge preys has been analyzed. In bioassays, sanyagunin B showed moderate antibacterial activity, whereas 4α-formamidogorgon-11-ene exhibited potent cytotoxicity with IC50 values ranging from 0.87 to 1.95â µM.
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Baías , Sesquiterpenos , Animais , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Espectroscopia de Ressonância Magnética , Cristalografia por Raios X , Estrutura MolecularRESUMO
A series of 1-O-acyl- and 1-oxo-kamebanin analogues were prepared from kamebanin, isolated from Rabdosia excisa and their cytotoxicity was assayed on HL60 promyelocytic leukemia cells and HCT116 human colon cancer cells. The structure-activity relationship study showed that the presence of 1-O-acyl groups of a C3-C5 carbon chain increased the cytotoxic activity.
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Antineoplásicos , Isodon , Humanos , Antineoplásicos/farmacologia , Relação Estrutura-Atividade , Células HL-60 , Células HCT116RESUMO
Two new glycerolipids, syngaculipids A and B (1 and 2), one first naturally occurring metabolite (8), together with five known compounds (3-7) were isolated from the AcOEt fraction of Syngnathus acus L. (Hai-Long). Their structures were elucidated by comprehensive spectral analyses involving UV, IR, MS, 1D and 2D NMR spectra and ECD calculations. All the isolated compounds were evaluated for their cytotoxicity against A549 and HCT-116â cell lines. Compound 8 exhibited moderate cytotoxicity with IC50 values of 34.5 and 38.9â µM on the A549 and HCT-116â cell lines, respectively.
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Medicina Tradicional Chinesa , Humanos , Estrutura Molecular , Células HCT116RESUMO
A new cembranolide, namely, sinupendunculide A (1), along with eight known related compounds (2-9), was isolated from the South China Sea Soft coral Sinularia pendunculata. The structure of sinupendunculide A (1) was established by extensive spectroscopic analysis and X-ray diffraction experiments. In a bioassay, anti-colorectal cancer (CRC) activity was performed, and the results showed that several compounds exhibited cytotoxicity against RKO cells, and a preliminary structure-activity relationship was analysed. Meanwhile, the most effective compound 7 was proven to increase reactive oxygen species levels, which promoted cell apoptosis and inhibited cell proliferation.
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Antozoários , Antineoplásicos , Diterpenos , Neoplasias , Animais , Antozoários/química , China , Diterpenos/farmacologia , Diterpenos/química , Estrutura Molecular , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/prevenção & controleRESUMO
Phidianidines A and B are novel marine indole alkaloids with various biological activities. Based on their potential anti-inflammatory properties, a series of phidianidine derivatives were designed, synthesized, and tested for their effects on IL-17A production in PMA/ionomycin-stimulated T-cell-lymphoma EL-4 cells. Compounds 9a and 22c exhibited excellent anti-inflammatory activity and low toxicity, with IC50 values of 7.7 µM and 5.3 µM for IL-17A production in PMA/ionomycin-stimulated EL-4 cells, respectively. Further mechanistic study showed that 9a could decrease the STAT3 phosphorylation at Y705 to inhibit IL-17A production in EL-4 cells, indicating its ability of preventing the differentiation of Th17 cells and their possible function. This research may give an insight for the discovery of marine indole alkaloid derived anti-inflammatory drug leads for the treatment of T cell-mediated diseases.
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Alcaloides Indólicos , Interleucina-17 , Anti-Inflamatórios/farmacologia , Ionomicina , Relação Estrutura-AtividadeRESUMO
Natural product dimers have intriguing structural features and often have remarkable pharmacological activities. We report here two uncommon marine gorgonian-derived symmetric dimers, weizhouochrones A (1) and B (2), with indenone-derived monomers, that were isolated from the coral Anthogorgia ochracea collected from the South China Sea. These dimers are difficult targets for structure elucidation that solely relies upon conventional NMR data such as NOEs and J-couplings. Here, to explore the application of emerging methods on the structure elucidation of challenging molecules, we explored a number of different anisotropic and computational NMR approaches. The measurements of anisotropic NMR parameters of weizhouochrone A, including residual dipolar couplings (RDCs) and residual chemical shift anisotropy (RCSA), allowed us to successfully determine the planar structure and its relative configuration. This result was corroborated by a computational NMR analysis based on DP4+ probability and computer-assisted 3D structure elucidation (CASE-3D).
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Antozoários , Produtos Biológicos , Animais , Anisotropia , Antozoários/química , Produtos Biológicos/química , Espectroscopia de Ressonância Magnética/métodos , ProbabilidadeRESUMO
Natural polybrominated diphenyl ethers, often isolated from marine sponges, have been reported to possess various biological activities, such as antibacterial, antioxidant and antidiabetic effects. Via a high throughput screening of our marine natural product library, the polybrominated diphenyl ether 3 was found to display a KCNQ potassium channel activation effect. To obtain more compound 3 related natural products and their derivatives for further bioactivity study, a diversity-oriented synthesis was conducted, leading to the successful synthesis of five polybrominated diphenyl ether natural products (1-4, 6) and 30 new derivatives. Compound 3 was found to preferentially potentiate KCNQ1 potassium channel, whereas 17h relatively activated KCNQ2 potassium channel. The structure-activity relationship was analyzed assisted by molecular docking and 17h was further conducted for its agonistic mechanism study on KCNQ2 channel. This research work may give an insight for the discovery of marine polybrominated diphenyl ether derived new drug leads.
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Produtos Biológicos , Poríferos , Animais , Produtos Biológicos/farmacologia , Éteres Difenil Halogenados/farmacologia , Canais de Potássio KCNQ , Simulação de Acoplamento MolecularRESUMO
Two new cladiellin-type diterpenoids (1 and 2) and four known related compounds 3-6, were isolated from the South China Sea soft coral Cladiella krempfi. Compound 2 is the third example of cladiellins of an unusual peroxy group in the C-6 position in C. krempfi. The structures and absolute configurations of the new compounds were established by extensive spectroscopic analysis, X-ray diffraction, and/or chemical correlation. In bioassay, all the compounds were evaluated for cytotoxicity and epidermal growth factor receptor (EGFR) inhibitory activity. A molecular docking experiment was conducted to study the structure-activity relationship of cladiellin-type diterpenoids on EGFR inhibitory activity.
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Antozoários , Diterpenos , Animais , Antozoários/química , China , Diterpenos/química , Receptores ErbB , Simulação de Acoplamento Molecular , Estrutura Molecular , EsteroidesRESUMO
Three complex polyoxygenated diterpenoids possessing uncommon tetradecahydro-2,13:6,9-diepoxybenzo[10]annulene scaffold, namely ximaoornatins A-C (1-3), one new eunicellin-type diterpene, litophynin K (4), and a related known compound, litophynol B (5) were isolated from the South China Sea soft coral Sinularia ornata. The structures and absolute configurations of 1-4 were established by extensive spectroscopic analysis, X-ray diffraction analysis, and/or modified Mosher's method. A plausible biosynthetic relationship of 1 and its potential precursor 4 was proposed. In a bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF-α release in RAW264.7 macrophages and PTP1B inhibitory effects.
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Antozoários/química , Produtos Biológicos , Diterpenos , Animais , Antozoários/metabolismo , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/metabolismo , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Modelos Moleculares , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/química , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Chemical investigation of the Hainan soft coral Sinularia hirta resulted in the isolation and identification of a library of sixteen structurally diverse terpenoids, including a dinorditerpenoid with an uncommon 17,19-dinorxeniaphyllane skeleton, namely sinuhirtone A (7), six new xeniaphyllane-type diterpenoids (1-6), one new norxeniaphyllanoid (8), two new norcaryophyllene-type sesquiterpenoids (9 and 10), together with six known related compounds (11-16). Compounds 1-3 are three new furanone-containing xeniaphyllane-type diterpenoids. The structures of the new compounds, including their absolute configurations, were determined by extensive spectroscopic analysis and a series of quantum chemical calculations, including quantum mechanical-nuclear magnetic resonance (QM-NMR), time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD), and optical rotatory dispersion (ORD) methods. A plausible biosynthetic connection between new compounds 1-9 was also proposed. New compounds 2-4, 7, and 8 were evaluated for in vitro cytotoxicity against four cancer cell lines.
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Antozoários , Diterpenos , Sesquiterpenos , Animais , Antozoários/química , Teoria da Densidade Funcional , Diterpenos/química , Diterpenos/farmacologia , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Terpenos/química , Terpenos/farmacologiaRESUMO
Six new pairs of γ-pyrone polypropionate enantiomers with an unusual peroxyl bridge at the side chain, namely (±)-ocellatuperoxides A-F (1-6), were isolated and characterized from the South China Sea photosynthetic mollusk Placobranchus ocellatus. Extensive spectroscopic analysis, single crystal X-ray diffraction analysis, ECD- (electronic circular dichroism) comparison, and TDDFT (time-dependent density functional theory) ECD computation were used to determine the structures and absolute configurations of new compounds. In a cell viability assay, several compounds showed considerable anti-tumoral effects on human non-small cell lung cancer cells A549 with Gefitinib (7.4 µM) and Erlotinib (2.1 µM) as positive controls. Further RNA-sequencing analysis and gene expression evaluation indicated that the anti-tumoral activity of the most effective compound 3 was associated with the regulation of several important genes, such as FGFR1 and HDAC5.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Humanos , Pironas/química , Estrutura Molecular , Peróxidos , Cloridrato de Erlotinib , Gefitinibe , Moluscos/química , Dicroísmo Circular , RNARESUMO
The chemical investigation of the South China Sea soft coral Sinularia humilis has resulted in the isolation of a library of diverse diterpenoids, including four new cembranoids, namely, humilisins A-D (1-4), two new uncommon diterpenoids possessing a tetradecahydrocyclopenta[3',4']cyclobuta[1',2':4,5]cyclonona[1,2-b]oxirene ring system, namely, humilisins E and F (5 and 6), and eight known related compounds (7-14). Humilisin A (1) is the first cembranoid with an ether linkage between C-3 and C-7. The structures and absolute configurations of 1-8 were determined by extensive spectroscopic data analyses, chemical reactions, and a series of quantum chemical calculations including quantum mechanical-nuclear magnetic resonance (QM-NMR), time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD), and optical rotatory dispersion (ORD) methods. In bioassay, compound 6 displayed anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.
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Antozoários , Diterpenos , Animais , China , Diterpenos/farmacologia , Lipopolissacarídeos/farmacologia , Estrutura MolecularRESUMO
A novel diterpenoid, sinueretone A (1), featuring an unprecedented tricyclo[12.1.0.05,9]pentadecane carbon framework, along with two new (2 and 3) and one known (4) casbane diterpenoids were isolated from the South China Sea soft coral Sinularia erecta. The structures of the new compounds, especially their absolute stereochemistry, were established by extensive spectroscopic analysis, various quantum chemical calculations, and/or X-ray diffraction analyses. A plausible biogenetic relationship of 1-4 was proposed, which gave an insight for future biomimetic synthesis of the novel compounds. In a bioassay, compounds 1 and 2 displayed interesting anti-inflammatory activity by the inhibition of lipopolysaccharide-induced tumor necrosis factor-α protein release.
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Antozoários , Diterpenos , Alcanos , Animais , Carbono , Estrutura MolecularRESUMO
Eleven novel cembranoid derivatives were designed, synthesized, and evaluated for their inflammation related activities on the basis of our isolated and previously reported anti-inflammatory marine cembranoids. In bioassay, compound 11 displayed the most promising inhibitory effects with IC50 value of 1.1 µM for the TNF-α inhibitory activity. The further mechanism study of 11 on the inflammatory signaling transduction of RAW264.7 cells was also performed. This research may give an insight for the discovery of marine cembranoid derived anti-inflammatory drug leads.
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Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Células Cultivadas , Diterpenos/síntese química , Diterpenos/química , Relação Dose-Resposta a Droga , Camundongos , Modelos Moleculares , Estrutura Molecular , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
A further systematically chemical investigation of the South China Sea soft coral Sinularia erecta led to the discovery of two rare casbane diterpenoids with an uncommon 8,10-peroxide bridge, sinuereperoxides B (1) and C (2), five new casbanes with other oxygenated patterns (3-7), and seven known casbanes (8-14). The structures and absolute configurations of 1-7 were established by extensive spectroscopic data analyses, X-ray diffraction analysis, and/or quantum chemical calculations. In bioassay, compounds 2, 7, 11 and 12 exhibited considerable anti-inflammatory activity by the inhibition of TNF-α release, with IC50 values of 33.8 µM, 5 µM, 9.9 µM and 8 µM.
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Antozoários/química , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Peróxidos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Camundongos , Peróxidos/química , Peróxidos/isolamento & purificação , Células RAW 264.7 , EstereoisomerismoRESUMO
Eight new dammarane-type triterpenoids (1-8), together with a related known analogue (9), were isolated from the roots of Rhus chinensis, a traditional Chinese medicine for treating coronary artery heart disease, guided by LC-MS analysis. Their structures were elucidated based on extensive spectroscopic analysis and quantum chemical calculations. Notably, compounds 1-7 and 9 possess an unusual 17α-side chain, and 1-4, 6, and 9 contain an uncommon 3-methyl-5,6-dihydro-2H-pyran-2-one moiety in the side chain. Compounds 1-5 and 9 have a 3,19-hemiketal bridge in the A ring. In an in vivo bioassay, 1, 2, and 4-6 exhibited significant preventive effects on zebrafish heart failure at 0.5 µg/mL, improving heart dilatation, venous congestion, cardiac output, blood flow velocity, and heart rate. Compound 5, displaying the most promising heart failure preventive activities, showed even better effects on increasing cardiac output (72%) and blood flow velocity (83%) than six first-line heart failure therapeutic drugs. Moreover, 1, 2, and 6 prevented the formation of thrombosis in zebrafish at 0.5 µg/mL. The present investigation suggests that the new dammarane triterpenoids might be partially responsible for the utility of R. chinensis in treating coronary artery heart disease.