RESUMO
Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1â³-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.
Assuntos
Aspergillus , Imunossupressores , Aspergillus/química , Humanos , Imunossupressores/farmacologia , Imunossupressores/química , Imunossupressores/isolamento & purificação , Estrutura Molecular , Cristalografia por Raios X , Interleucina-6/metabolismo , Antraquinonas/farmacologia , Antraquinonas/química , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Linfócitos T/efeitos dos fármacos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacosRESUMO
Twelve new austalide meroterpenoids (1-12) were isolated from the endophytic fungus Diaporthe sp. XC1211. Their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of compounds 1, 3, 4, and 6 were established by single-crystal X-ray diffraction, whereas those for the others were established by experimental electronic circular dichroism (ECD) data analysis. Compounds 1-12 represent a rare class of austalides with a 24α-CH3. Compounds 2 and 5 demonstrated potent proliferation inhibitory effects against LPS-induced B cells with IC50 values of 6.7 (SI = 3.6) and 3.8 (SI > 13) µM, respectively. Compounds 2 and 5 decreased the secretion of IL-6 in LPS-induced B cells in a dose-dependent manner.
Assuntos
Fungos , Lipopolissacarídeos , Estrutura Molecular , Lipopolissacarídeos/farmacologia , Cristalografia por Raios X , Dicroísmo CircularRESUMO
Podomycins A-L (1-12), 12 undescribed hypothemycin-type resorcylic acid lactones (RALs), were characterized from Podospora sp. G214, an endophyte harbored in the roots of Sanguisorba officinalis L. Their structures were addressed by spectroscopic data, X-ray crystallography, the modified Mosher's method, together with Mo2(OAc)4- and Rh2(OCOCF3)4-induced electronic circular dichroism (ICD) experiments. Podomycins A-C (1-3) represent the first class of natural RALs with a 13-membered macrolactone ring, while 4-12 are rearranged methoxycarbonyl substituted RALs. Biologically, compounds 2, 6, 8, 10, and 12 displayed immunosuppressive activities against T cell proliferation with IC50 values of 14.5-21.9 µM, and B cell proliferation with IC50 values of 22.3-36.5 µM, respectively. Further mechanism of action research demonstrated that podomycin F (6) distinctly induced apoptosis in activated T cells via MAPKs/AKT pathway.
Assuntos
Apoptose/efeitos dos fármacos , Imunossupressores/farmacologia , Lactonas/farmacologia , Podospora/química , Linfócitos T/efeitos dos fármacos , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Imunossupressores/química , Imunossupressores/isolamento & purificação , Lactonas/química , Lactonas/isolamento & purificação , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Proteínas Proto-Oncogênicas c-akt , Relação Estrutura-Atividade , Linfócitos T/metabolismoRESUMO
Eleven previously undescribed radicicol-type resorcylic acid lactones (RALs), namely ilyomycins A - K (1-9, 10a and 10b), were isolated and identified from the fermented rice culture of a soil-derived fungus, Ilyonectria sp. (strain sb65). Their gross structures were determined by extensive spectroscopic data, and the absolute configurations were elucidated by single-crystal X-ray diffraction, the modified Mosher's method, and Rh2(OCOCF3)4-induced electronic circular dichroism (ICD) experiment. Among them, 10a and 10b were a pair of inseparable regioisomers via intramolecular transacetylation. Compounds 3, 7, 8 and 10a/10b displayed immunosuppressive activities against T cell proliferation with IC50 values ranging from 1.2 to 21.7 µM, and against B cell proliferation with IC50 values ranging from 1.1 to 20.1 µM, which suggested that the α, ß-unsaturated ketone from C-8 to C-10 was an important pharmacophore. Further study revealed that ilyomycin C (3) exerted anti-proliferative effect on T lymphocytes through Hsp90 inhibition.
Assuntos
Hypocreales , Lactonas , Imunossupressores/farmacologia , Lactonas/química , Lactonas/farmacologia , Macrolídeos , Estrutura Molecular , SoloRESUMO
Fourteen new [11]-chaetoglobosins (1-14), along with two known congeners, cytochalasins X and Y (15 and 16), were isolated from the cultures of an endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures incorporating absolute configurations were elucidated based on the comprehensive analyses of one- and two-dimensional NMR data, HRESIMS spectrometry, chemical methods, and single-crystal X-ray diffraction analysis (Cu Kα). All isolates were evaluated for their cytotoxic activities and chaetopseudeurin M (1) displayed significant cytotoxic effects against seven human cancer cell lines, with IC50 values ranging from 5.1 ± 0.9 to 10.8 ± 0.1 µM. Western blot experiments exhibited that compound 1 exerted its cytotoxic effect in MCF-7 cells by inducing G2/M cell cycle arrest and apoptosis via downregulating the expression of cyclin B1 and Cdk1, and activating Bcl-2/caspase-3/PARP pathway, respectively.
Assuntos
Antineoplásicos , Ascomicetos , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Pontos de Checagem da Fase G2 do Ciclo Celular , Humanos , Alcaloides IndólicosRESUMO
Twelve new [11]-chaetoglobosins, chaetopseudeurins A-L (1-12), were identified from the fermentation of the endophytic fungus Pseudeurotium bakeri P1-1-1. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. Compounds 2 and 5-7 exhibited significant cytotoxicities against seven human cancer cell lines, with IC50 values ranging from 4.7 ± 1.0 to 12.2 ± 0.7 µM, and induced G2/M cell cycle arrest and apoptosis in MCF-7 and A427 cells dose dependently. Western blot analysis showed that compound 2 induced apoptosis of MCF-7 cells via the Bcl-2/caspase-3/PARP pathway.
Assuntos
Apoptose/efeitos dos fármacos , Ascomicetos/química , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Linhagem Celular Tumoral , China , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Alcaloides Indólicos/isolamento & purificação , Células MCF-7 , Estrutura MolecularRESUMO
Twelve new hypothemycin-type resorcylic acid lactones, three 10-membered (1-3) and nine 14-membered (4-12), together with seven known analogues (13-19), were obtained from the solid rice-based culture of Podospora sp. G214. Their structures were elucidated utilizing spectroscopic analysis, and the absolute configurations were determined by modified Mosher's method, Mo2(OAc)4-induced electronic circular dichroism experiments, and single-crystal X-ray diffraction. Compounds 1, 5, 10, and 12-19 exhibited potent immunosuppressive activities against concanavalin A-induced T cell proliferation with IC50 values ranging from 6.0 to 25.1 µM and lipopolysaccharide-induced B cell proliferation with IC50 values ranging from 6.2 to 29.1 µM. Further studies revealed that 1 induced apoptosis in activated T cells through the JNK-mediated mitochondrial pathway.
Assuntos
Linfócitos B/efeitos dos fármacos , Imunossupressores/farmacologia , Lactonas/farmacologia , Podospora/química , Linfócitos T/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , China , Imunossupressores/isolamento & purificação , Lactonas/isolamento & purificação , Masculino , Camundongos Endogâmicos BALB C , Estrutura Molecular , Raízes de Plantas/microbiologia , Sanguisorba/microbiologia , Baço/citologia , Zearalenona/análogos & derivados , Zearalenona/isolamento & purificação , Zearalenona/farmacologiaRESUMO
Fifteen new highly oxygenated eremophilane sesquiterpenoids, parasubolides A-O (1-15), were obtained from the whole plant of Parasenecio albus. The structures of 1-15 were elucidated based on the interpretation of NMR and HRESIMS data, along with experimental electronic circular dichroism (ECD) and single-crystal X-ray diffraction analysis. Compounds 1-6, and 9-14 represent the first class of 1,2,10-trioxygenated eremophilane lactones. Selected isolates were evaluated for their immunosuppressive activities. Compounds 4, 5, and 12 exhibited moderate inhibition against LPS-induced B-cell proliferation with IC50 values of 23.1, 33.8, and 26.6 µM, respectively.
Assuntos
Asteraceae/química , Linfócitos B/efeitos dos fármacos , Imunossupressores/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Imunossupressores/química , Imunossupressores/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/isolamento & purificação , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Twelve new resorcylic acid lactones (RALs) including three new 16-membered RALs (1a, 1b and 2), eight new 14-membered RALs (3-10), and one new 12-membered RAL (11), along with five known 14-membered RALs (12-16), were identified from the fermentation of the soil-derived fungus Ilyonectria sp. sb65. Their structures were established by detailed analyses of 1D and 2D NMR, HRESIMS, and X-ray diffraction crystallography. All new compounds were evaluated for their cytotoxic effects against three human cancer cell lines, along with their potential as TRAIL sensitizers in TRAIL-resistant A549 human lung adenocarcinoma cells and their in vitro immunosuppressive effects against ConA-induced T-cell and LPS-induced B-cell proliferation.
Assuntos
Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Hypocreales/química , Lactonas/química , Lactonas/farmacologia , Resorcinóis/química , Animais , Linhagem Celular Tumoral , Cristalografia por Raios X , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fermentação , Células HeLa , Humanos , Imunossupressores/farmacologia , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Resorcinóis/farmacologiaRESUMO
Ten new alkaloids (1-10), including two pairs of enantiomeric mixtures (5a,b and 6a,b), and 15 known analogues (11-25) were obtained from the bark of Pausinystalia yohimbe. The structures of 1-25 were established by spectroscopic methods, and the absolute configurations of compounds 1-10 were resolved by X-ray diffraction and ECD data analyses. The in vitro immunosuppressive activities of selected isolates were tested. Compounds 11 and 16 exhibited moderate inhibition with IC50 values of 16.8 and 27.6 µM against ConA-induced T lymphocyte proliferation and 13.5 and 40.5 µM against LPS-induced B lymphocyte proliferation, respectively.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Imunossupressores/química , Imunossupressores/farmacologia , Pausinystalia/química , Casca de Planta/química , Animais , Linfócitos B/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dicroísmo Circular , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Difração de Raios XRESUMO
Nine new lignans (1-9) and ten known analogues (10-19) were isolated from the fruits of Schisandra bicolor var. tuberculata. The structures of compounds 1-9 were established on the basis of spectroscopic data analysis. The absolute configuration of compound 1 was determined by single-crystal X-ray diffraction analysis with Cu Kα irradiation techniques, and the absolute configurations of compounds 2-9 were deduced by comparing their experimental ECD spectra and optical rotations with those of compound 1 or similar compounds. All isolates were evaluated for their neuroprotective activities against CoCl2, H2O2, and Aß25-35-induced SH-SY5Y cell injury, and were found to exhibit different degrees of neuroprotective effects. At a low concentration of 3.2 nM, compounds 3, 8, 9, and 14-19 in CoCl2-induced, compounds 7, 8, 13, 17, and 18 in H2O2-induced, and compounds 2, 6, 7, 9, 10, and 12-19 in Aß25-35-induced SH-SY5Y cell injury models, showed statistically significant neuroprotective activities, when compared with each negative control group.
Assuntos
Frutas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Schisandra/química , Peptídeos beta-Amiloides/efeitos dos fármacos , Peróxido de Hidrogênio/análise , Lignanas/química , Conformação Molecular , Estrutura Molecular , Fármacos Neuroprotetores/química , Fragmentos de Peptídeos/efeitos dos fármacos , Difração de Raios XRESUMO
A family of nonlinear optical materials that contain the halide, oxide, and oxyhalide polar units simultaneously in a single structure, namely ABi2 (IO3 )2 F5 (A=K (1), Rb (2), and Cs (3)), have been designed and synthesized. They crystallize in the same polar space group (P21 ) with a two-dimensional double-layered framework constructed by [BiF5 ]2- and [BiO2 F4 ]5- units connected to each other by four F atoms, in which two [IO3 ]- groups are linked to [BiO2 F4 ]5- unit on the same side. A hanging Bi-F bond of [BiF5 ]2- unit is located on the other side via ionic interaction with the layer-inserted alkali metal ions to form three-dimensional structure. The well-ordered alignments of these polar units lead to a very strong second-harmonic generation response of 12 (1), 9.5 (2), and 7.5 (3) times larger than that of potassium dihydrogen phosphate under 1064â nm laser radiation. All of them exhibited a wide energy bandgap over 3.75â eV, suggesting that they will have a high laser damage threshold.
RESUMO
The synthesis and characterization of a series of biphenyl-derived binuclear ruthenium complexes with terminal {RuCl(CO)(PMe3)3} moieties and different structural arrangements of the phenyl rings are reported. Electrochemical studies revealed that the two metal centers of the binuclear ruthenium complexes interact with each other through the biphenyl bridge, and the redox splittings ΔE1/2 show a strong linear correlation with cos(2) Ï, where Ï is the torsion angle between the two phenyl rings. A combination of electrochemical, UV/Vis/NIR, and in situ IR differential spectroelectrochemical analysis clearly showed that: 1)â the intramolecular electronic couplings in the binuclear ruthenium complexes could be modulated by changing Ï; 2)â the electronic ground state of the mixed-valent cations changes from delocalized to localized through the biphenyl bridge with increasing torsion angle Ï, that is, the redox processes of these complexes change from significant involvement of the bridging ligand to an oxidation behavior with less participation of the bridge.
RESUMO
This paper described a decarboxylative deaminative dual-coupling reaction of amino acids with indoles to afford BIM scaffolds and its further application to the one-pot total synthesis of natural products. This method featured a stimulating example of activating amino acids in one pot as multi-carbon building blocks for transformation into final targets which are equipped with amino acid side chain backbones.
Assuntos
Acetatos/química , Acetatos/síntese química , Aminoácidos/química , Produtos Biológicos/química , Produtos Biológicos/síntese química , Butiratos/química , Butiratos/síntese química , Indóis/química , Indóis/síntese química , Técnicas de Química SintéticaRESUMO
This paper describes the synthesis, crystal structure, and photophysical properties of a new compound Rb2CdBr2I2. It crystallizes in the noncentrosymmetric space group Ama2. In the crystal, all the distorted tetrahedron [CdBr2I2](2-) groups are arranged in a way such that all the Cd-I bonds are located in the same side of the Cd atoms resulting in a net polarization. Rb2CdBr2I2 showed a powder second harmonic generation (SHG) response 4 times that of KH2PO4 (KDP). The preliminary measurement indicated that it exhibits a large laser-induced damage threshold (LDT) of 190 MW/cm(2) which is 6 times that of AgGaS2. It also exhibits a wide transparent region (0.37-14 µm) with a relatively high (up to 490 °C) thermal stability. All these indicate that Rb2CdBr2I2 is a new promising candidate for NLO materials in the IR region.
RESUMO
A novel TPE-based expanded oxacalixarene with typical aggregation-induced emission properties was synthesized by the SNAr reaction of dihydroxytetraphenylethylene with 2,6-dichloropyrazine. The conformation of the oxacalixarene is adjusted by the encapsulated guests (benzene or THF), which results in different supramolecular grid structures in the solid state.
Assuntos
Calixarenos/síntese química , Etilenos/química , Corantes Fluorescentes/química , Substâncias Macromoleculares/síntese química , Calixarenos/química , Cristalografia por Raios X , Substâncias Macromoleculares/química , Estrutura Molecular , Pirazinas/síntese química , Pirazinas/químicaRESUMO
Imide-modified polycyclic aromatic hydrocarbons can be widely applied in the field of optoelectronic materials. In this work, we have synthesized four novel functionalized benzopicenes and characterized their solid structures and optoelectronic properties. The fluorescence of the four functionalized benzopicenes showed red shifts with increasing solvent polarity; the quantum yields are high in the solution state and moderate in the solid state. The single crystal structures show that the benzopicenes adopt a lamellar motif π-stacking. Their good solubility and optoelectronic properties make them potential solution-processable candidates for organic devices, bioimaging and biolabeling.
Assuntos
Técnicas Eletroquímicas , Imidas/química , Hidrocarbonetos Policíclicos Aromáticos/química , Estrutura Molecular , Hidrocarbonetos Policíclicos Aromáticos/síntese químicaRESUMO
Ten previously unreported [11]-chaetoglobosins, chaepseubakerins A-J (1-10), were characterized from the solid rice-based culture of Pseudeurotium bakeri P1-1-1, an endophyte harbored in the roots of Macrocoma tenue subsp. sullivantii Vitt. (Orthotrichaceae). Their structures were determined by spectroscopic analysis, single-crystal X-ray diffraction (Cu Kα radiation), and chemical methods. Chaepseubakerin A (1) exhibited significant cytotoxic effects against seven human cancer cell lines, A549, A427, HCT116, HT-29, HeLa, HepG2, and MCF-7, with IC50 values of 2.9, 3.0, 4.0, 4.4, 7.1, 6.7, and 8.9 µM, respectively. Mechanistically, 1 induced G2/M cell cycle arrest and apoptosis in A549, Hela, and HCT116 cells in a dose dependent manner.
Assuntos
Antineoplásicos , Ascomicetos , Alcaloides Indólicos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Células HeLa , Apoptose , Estrutura MolecularRESUMO
In the pursuit of advancing materials for methane storage, a critical consideration arises given the prominence of natural gas (NG) as a clean transportation fuel, which holds substantial potential for alleviating the strain on both energy resources and the environment in the forthcoming decade. In this context, a novel approach is undertaken, employing the rigid triptycene as a foundational building block. This strategy is coupled with the incorporation of dichloromethane and 1,3-dichloropropane, serving as rigid and flexible linkers, respectively. This combination not only enables cost-effective fabrication but also expedites the creation of two distinct triptycene-based hypercrosslinked polymers (HCPs), identified as PTN-70 and PTN-71. Surprisingly, despite PTN-71 manifesting an inferior Brunauer-Emmett-Teller (BET) surface area when compared to the rigidly linked PTN-70, it showcases remarkably enhanced methane adsorption capabilities, particularly under high-pressure conditions. At a temperature of 275 K and a pressure of 95 bars, PTN-71 demonstrates an impressive methane adsorption capacity of 329 cm3 g-1. This exceptional performance is attributed to the unique flexible network structure of PTN-71, which exhibits a pronounced swelling response when subjected to elevated pressure conditions, thus elucidating its superior methane adsorption characteristics. The development of these advanced materials not only signifies a significant stride in the realm of methane storage but also underscores the importance of tailoring the structural attributes of hypercrosslinked polymers for optimized gas adsorption performance.