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1.
J Nat Prod ; 83(6): 1804-1809, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32539381

RESUMO

Hypersonins A-D (1-4), four 1,2-seco-homoadamantane type polycyclic polyprenylated acylphloroglucinols (PPAPs) possessing a new bicyclo[4.3.1]decane-3-methoxycarbonyl architecture, were obtained from Hypericum wilsonii. The structures of hypersonins A-D were identified by spectroscopic data, electronic circular dichroism comparison, and X-ray crystallographic data. Hypersonins A-D are the first seco-homoadamantane-type PPAPs with cleavage at the C-1-C-2 bond. Hypersonin A (1) showed moderate inhibitory activity to anti-CD3/anti-CD28 monoclonal antibody-induced proliferation of murine splenocytes, with an IC50 value of 8.3 ± 0.2 µM.

2.
Bioorg Chem ; 99: 103816, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32305693

RESUMO

Three previously undescribed compounds, including a meroterpenoid, guignardone T (1), and two ophiobolin-type sesterterpenoids, maydispenoids A and B (2 and 3), along with four known compounds (4-7), were isolated from the phytopathogenic fungus Bipolaris maydis collected from Anoectochilus roxburghii (Wall.) Lindl leaves. The structures of all undescribed compounds were elucidated by spectroscopic analysis, electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction. Structurally, maydispenoids A was characterized by a fascinating decahydro-3-oxacycloocta[cd]pentalene fragment. It is notable that the compounds 2 and 3 exhibited potential inhibitory activity in anti-CD3/anti-CD28 monoclonal antibodies (mAbs) stimulated murine splenocytes proliferation, with IC50 values of 5.28 and 9.38 µM, respectively, and also suppress the murine splenocytes proliferation activated by lipopolysaccharide (LPS), with IC50 values of 7.25 and 16.82 µM, respectively. This is the first report of ophiobolin-type sesterterpenoids as immunosuppressor, and may provide new chemical templates for the development of new immunosuppressive drugs for autoimmune disease treatment.

3.
Phytochemistry ; 175: 112374, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32315839

RESUMO

Seven undescribed alkaloids, namely fischeramides A and B, 5,6-dimethoxycircumdatin C, 6-hydroxyacetylaszonalenin, 3-methoxyglyantrypine, 9-methoxyfumitremorgin C, and spirotryprostatin M, one undescribed natural product, namely 11-deacetyl pyripyropene A, together with nine known congeners, were isolated from the solid cultures of fungus Neosartorya fischeri, which was separated from a medicinal insect Cryptotympana atrata. Their structures were elucidated by extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analyses. Structurally, fischeramides A and B represented a pair of rare geometric isomers of the benzodiazepinedione derivatives with a highly conjugated feature. Fischeramide A showed potential immunosuppressive activity in LPS and anti-CD3/anti-CD28 mAbs activated murine splenocytes proliferation with IC50 values of 7.08 and 6.31 µM, respectively, and also showed anti-inflammatory activity against the lipopolysaccharide-induced nitric oxide production with an IC50 value of 25 ± 1 µM. In addition, 5,6-dimethoxycircumdatin C showed remarkable antibacterial activity against ESBL-producing E. coli with an MIC value of 2.0 µg/mL.


Assuntos
Alcaloides , Neosartorya , Animais , Aspergillus , Escherichia coli , Insetos , Camundongos
4.
Phytochemistry ; 173: 112295, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32113065

RESUMO

Four undescribed bioxanthracene derivatives, dongtinganthracenes A-D, along with a previously reported analog, ES-242-3, were obtained from the solid culture broth of the fungus Penicillium sp. DT10, which was isolated from wetland soil obtained from Dongting Lake. Their structures and absolute configurations were elucidated based on extensive NMR analyses, mass spectroscopic analyses, and ECD calculations. Dongtinganthracene A represents the first 7',8'-seco-bioxanthracene produced via oxidation, and dongtinganthracenes A-D show a much higher degree of oxidation in aromatic rings compared with normal naturally occurring bioxanthracene derivatives. Dongtinganthracenes B and D and ES-242-3 exhibit cytotoxic activity, while dongtinganthracene A shows inhibitory activity against LPS-induced NO production.


Assuntos
Penicillium , Lagos , Estrutura Molecular , Solo , Áreas Alagadas
5.
Fitoterapia ; 143: 104532, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32151636

RESUMO

Six new compounds, including two new isochromane lactones, versicoisochromanes A and B (1 and 2), two new benzolactones, versicobenzos A and B (3 and 4), one furancarboxylic derivate, asperfuran A (6) and one ergosterol-type steroid, asperergoster A (7), along with five known steroids (8-12), were isolated from the Anoectochilus roxburghii endophytic fungus Aspergillus versicolor. The structures of these new compounds were determined by extensive spectroscopic techniques and electronic circular dichroism (ECD) calculations. It is notable that the new compound 7 exhibited obvious IL-1ß, NO and TNF-α inhibitory activity in LPS-stimulated RAW264.7 macrophages, with IC50 values of 35.5, 33.9 and 31.3 µM, respectively. Furthermore, compounds 7 and 8 displayed potential inhibitory effects on murine splenocytes proliferation stimulated by anti-CD3/anti-CD28 monoclonal antibodies (mAbs), meanwhile suppress the lipopolysaccharide (LPS) irritated murine splenocytes proliferation.

6.
J Nat Prod ; 82(10): 2925-2930, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31490677

RESUMO

A pyridone alkaloid, asperpyridone A (1), which possesses an unusual pyrano[3,2-c]pyridine scaffold, was isolated from solid cultures of the endophytic fungus Aspergillus sp. TJ23. Its structure, including its absolute configuration, was determined using a combination of nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, quantum chemical calculations (electronic circular dichroism), and X-ray crystallography. In vitro bioassays demonstrated that asperpyridone A (1) could function as a potential hypoglycemic agent, which exhibited pronounced glucose uptake effect in liver HepG2 cells, under both normal and insulin-resistant conditions, with higher efficacy than metformin. The underlying mechanism of asperpyridone A was elucidated by analyzing the genes expressed, the Gene Ontology (GO) function enrichment, the protein interaction network, and real-time quantitative reverse transcription polymerase chain reaction, which suggested that asperpyridone A exhibits hypoglycemic activity by activating the insulin signaling pathway. Moreover, on the basis of the hypoglycemic potency, fibroblast growth factor 21 (FGF21) was determined to be a potential target for asperpyridone A.

7.
Cell Commun Signal ; 17(1): 111, 2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470862

RESUMO

BACKGROUND: Distinctive from their normal counterparts, cancer cells exhibit unique metabolic dependencies on glutamine to fuel anabolic processes. Specifically, pancreatic ductal adenocarcinoma (PDAC) cells rely on an unconventional metabolic pathway catalyzed by aspartate transaminase 1 (GOT1) to rewire glutamine metabolism and support nicotinamide adenine dinucleotide phosphate (NADPH) production. Thus, the important role of GOT1 in energy metabolism and Reactive Oxygen Species (ROS) balance demonstrates that targeting GOT1 may serve as an important therapeutic target in PDAC. METHODS: To assay the binding affinity between Aspulvinone O (AO) and GOT1 proteins, the virtual docking, microscale thermophoresis (MST), cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) methods were employed. GOT1 was silenced in several PDAC cell lines. The level of OCR and ECR were assayed by seahorse. To evaluate the in vivo anti-tumor efficacy of AO, the xenograft model was built in CB17/scid mouse. RESULTS: Screening of an in-house natural compound library identified the AO as a novel inhibitor of GOT1 and repressed glutamine metabolism, which sensitizes PDAC cells to oxidative stress and suppresses cell proliferation. Virtual docking analysis suggested that AO could bind to the active site of GOT1 and form obvious hydrophobic interaction with Trp141 together with hydrogen bonds with Thr110 and Ser256. Further in vitro validation, including MST, CETSA and DARTS, further demonstrated the specific combining capacity of AO. We also show that the selective inhibition of GOT1 by AO significantly reduces proliferation of PDAC in vitro and in vivo. CONCLUSIONS: Taken together, our findings identify AO as a potent bioactive inhibitor of GOT1 and a novel anti-tumour agent for PDAC therapy.

8.
Org Biomol Chem ; 17(35): 8234-8242, 2019 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-31441489

RESUMO

Chemical investigation of the extracts of the aerial parts of Hypericum przewalskii Maxim. resulted in the isolation and identification of six new epoxychromene-containing polycyclic polyprenylated acylphloroglucinols (PPAPs), named przewalcyrones A-F (1-6), and one known analogue (7). All of the structures were determined based on extensive spectroscopic analyses, X-ray crystallographic analysis, modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD, and electronic circular dichroism (ECD) comparison. Structurally, przewalcyrones A-F represent the first examples of PPAPs containing an unexpected 8,8-dimethyl-3,9-epoxychromene moiety. All these compounds were evaluated for the immunosuppressive activity in anti-CD3/anti-CD28 monoclonal antibody (mAb)-stimulated human T cells. Among them, przewalcyrones C and D exhibited potential in vitro immunosuppressive activity, with IC50 values of (5.01 ± 0.52) µM and (5.26 ± 0.56) µM, respectively, highlighting those compounds as a promising starting point for the development of new immunosuppressive agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Hypericum/química , Imunossupressores/farmacologia , Floroglucinol/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Voluntários Saudáveis , Humanos , Imunossupressores/química , Imunossupressores/isolamento & purificação , Leucócitos Mononucleares/efeitos dos fármacos , Conformação Molecular , Floroglucinol/análogos & derivados , Floroglucinol/química , Estereoisomerismo , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
9.
Phytochemistry ; 164: 184-191, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158603

RESUMO

Eleven highly oxygenated meroterpenoids, named terreustoxins A-K, along with five known analogues, were isolated from the Antarctic fungus Aspergillus terreus. The structures and absolute configurations of these undescribed compounds were characterized by NMR spectroscopy, single-crystal X-ray crystallography, and ECD experiments. Terreustoxins A-D are the first examples of meroterpenoids with two ortho-hydroxy groups at C-6 and C-7 in the terretonins family. Terreustoxin C and terretonin inhibited the proliferation of Con A-induced murine T cells at the concentration of 10 µM.


Assuntos
Aspergillus/química , Oxigênio/farmacologia , Terpenos/farmacologia , Animais , Aspergillus/metabolismo , Proliferação de Células/efeitos dos fármacos , Concanavalina A , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Camundongos , Modelos Moleculares , Conformação Molecular , Oxigênio/química , Oxigênio/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Terpenos/química , Terpenos/metabolismo
10.
Phytochemistry ; 165: 112041, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31203103

RESUMO

Spiroterreusnoids A-F, six undescribed spiro-dioxolane-containing adducts bearing 3,5-dimethylorsellinic acid-based meroterpenoid and 2,3-butanediol moieties were isolated from the endophytic fungus Aspergillus terreus Thom from Tripterygium wilfordii Hook. f. (Celastraceae). The structures of these adducts were established by spectroscopy, single-crystal X-ray diffraction, and experimental electronic circular dichroism (ECD) measurements. Spiroterreusnoids A-F represent the first examples of adducts composed of 3,5-dimethylorsellinic acid-based meroterpenoids. It is noteworthy that spiroterreusnoids A-F possessing a spiro-dioxolane moiety exhibited potential abilities in inhibiting BACE1 (IC50 values ranging from 5.86 to 27.16 µM) and AchE (IC50 values ranging from 22.18 to 32.51 µM), while the other analogues without this fragment displayed no such activities. Taken together, spiroterreusnoids A-F represent the first multitargeted natural adducts that could inhibit BACE1 and AchE, and might provide a new template for the development of new anti-Alzheimer's disease drugs.


Assuntos
Acetilcolinesterase/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Dioxolanos/farmacologia , Inibidores Enzimáticos/farmacologia , Compostos de Espiro/farmacologia , Terpenos/farmacologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Aspergillus/química , Celastraceae/microbiologia , Dioxolanos/química , Dioxolanos/isolamento & purificação , Enguias , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Compostos de Espiro/química , Compostos de Espiro/isolamento & purificação , Terpenos/química , Terpenos/isolamento & purificação
11.
Org Biomol Chem ; 16(46): 9046-9052, 2018 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-30430177

RESUMO

Chemical investigation of the extracts of Aspergillus terreus resulted in the identification of terreusterpenes A-D (1-4), four new 3,5-dimethylorsellinic acid-based meroterpenoids. The structures and absolute configurations of 1-4 were elucidated by spectroscopic analyses including HRESIMS and 1D- and 2D-NMR, chemical conversion, and single crystal X-ray diffraction. Terreusterpenes A (1) and B (2) featured 2,3,5-trimethyl-4-oxo-5-carboxy tetrahydrofuran moieties. Terreusterpene D (4) was characterized by a 4-hydroxy-3-methyl gamma lactone fragment that was generated by accident from the rearrangement of 3 in a mixed tetrahydrofuran-H2O-MeOH solvent. All these compounds were evaluated for the ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AchE) inhibitory activities. Among them, compounds 1 and 2 showed potentially significant BACE1 inhibitory activity, with IC50 values of 5.98 and 11.42 µM, respectively. Interestingly, compound 4 exhibited promising BACE1 and AchE inhibitory activities, with IC50 values of 1.91 and 8.86 µM, respectively, while 3 showed no such activity. Taken together, terreusterpenes A and B could be of great importance for the development of new BACE1 inhibitors, while terreusterpene D could serve as the first dual-targeted 3,5-dimethylorsellinic acid-based meroterpenoid for the treatment of Alzheimer's disease.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Aspergillus/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Resorcinóis/química , Resorcinóis/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Inibidores da Colinesterase/síntese química , Cristalografia por Raios X , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/metabolismo , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Resorcinóis/síntese química
12.
Bioorg Med Chem ; 26(22): 5903-5910, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30392953

RESUMO

Chemical study on the extract of a marine-derived fungus Aspergillus terreus yielded twelve butenolide derivatives, including three new compounds, namely asperlides A-C (1-3) and nine known butenolides (4-12). The structures of 1-3 were confirmed by comprehensive spectroscopic analysis, including HRESIMS, NMR spectroscopy, and calculated electronic circular dichroism (ECD). The cytotoxicity of the compounds was evaluated using PANC-1, HCC1806, HepG2, BEAS-2B and HT-29 cancer cells. The results showed that (+)-3',3'-di-(dimethylallyl)-butyrolactone II (4) and versicolactone B (6) exhibited the most potent cytotoxin of PANC-1 cell line, with the IC50 values of 5.3 and 9.4 µM, respectively. Morphological features of apoptosis were observed in 4 and 6-treated PANC-1 cells, including apoptotic body formation, membrane blebbing, cell shrinkage and nuclear condensation. Cell cycle analysis with propidium iodide staining exhibited that 4 inhibits proliferation of PANC-1 cells via the induction of G2/M and S phase arrest, while 6 could retard the PANC-1 cells via the induction of S phase arrest. Flow cytometric analysis suggested that treatment with 4 and 6 significantly induced PANC-1 cells apoptosis. These findings indicated that 4 and 6 might serve as a starting point for the development of an anticancer drug for the treatment of pancreatic ductal adenocarcinoma.


Assuntos
4-Butirolactona/análogos & derivados , Antineoplásicos/farmacologia , Aspergillus/química , Carcinoma Ductal Pancreático/tratamento farmacológico , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carcinoma Ductal Pancreático/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Neoplasias Pancreáticas , Relação Estrutura-Atividade
13.
Org Biomol Chem ; 16(45): 8751-8760, 2018 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-30398284

RESUMO

Altering the cultivation conditions, such as temperature, media compositions, illumination, aeration, the shape of the culturing flask, etc., is regarded as a useful strategy for the exploitation of structurally novel and bioactive secondary metabolites, which inspired us to explore the chemical and pharmacological diversities from the genetically powerful fungus Alternaria brassicicola. As a result, twelve fusicoccane-type diterpenoids, including eight new ones, termed brassicicenes Q-X (1-8), were isolated from a modified rice medium. Biosynthetically, all these compounds were derived from the mevalonic acid (MVA) pathway, and their structures incorporating absolute configurations were assigned by the interpretation of spectroscopic (HRESIMS and 1D and 2D NMR) analyses, chemical conversion, a modified Mosher's method, 13C NMR calculation, and single-crystal X-ray diffraction (Cu Kα). Structurally, compound 1 was an unusual 16-nor-dicyclopenta[a,d]cyclooctane diterpenoid bearing a fused cyclopent-2-en-1-one moiety. In addition, compound 3 was found to show significant anti-inflammatory activity against the production of NO, TNF-α, and IL-1ß at 10 µM. Further western blot and immunofluorescence experiments found the mechanism of action to be that 3 inhibited the NF-κB-activated pathway, highlighting it as a promising starting point for the development of new anti-inflammatory agents.


Assuntos
Alternaria/química , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Diterpenos/química , Relação Dose-Resposta a Droga , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Camundongos , Modelos Moleculares , Conformação Molecular , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Fator de Transcrição RelA/metabolismo
14.
Front Chem ; 6: 422, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271773

RESUMO

Nine novel butenolide derivatives, including four pairs of enantiomers, named (±)-asperteretones A-D (1a/1b-4a/4b), and a racemate, named asperteretone E (5), were isolated and identified from the coral-associated fungus Aspergillus terreus. All the structures were established based on extensive spectroscopic analyses, including HRESIMS and NMR data. The chiral chromatography analyses allowed the separation of (±)-asperteretones A-D, whose absolute configurations were further confirmed by experimental and calculated electronic circular dichroism (ECD) analysis. Structurally, compounds 2-5 represented the first examples of prenylated γ-butenolides bearing 2-phenyl-3-benzyl-4H-furan-1-one motifs, and their crucial biogenetically related metabolite, compound 1, was uniquely defined by an unexpected cleavage of oxygen bridge between C-1 and C-4. Importantly, (±)-asperteretal D and (4S)-4-decarboxylflavipesolide C were revised to (±)-asperteretones B (2a/2b) and D (4), respectively. Additionally, compounds 1a/1b-4a/4b and 5 were evaluated for the α-glucosidase inhibitory activity, and all these compounds exhibited potent inhibitory potency against α-glucosidase, with IC50 values ranging from 15.7 ± 1.1 to 53.1 ± 1.4 µM, which was much lower than that of the positive control acarbose (IC50 = 154.7 ± 8.1 µM), endowing them as promising leading molecules for the discovery of new α-glucosidase inhibitors for type-2 diabetes mellitus treatment.

15.
J Nat Prod ; 81(9): 1937-1945, 2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-30207465

RESUMO

Sixteen 3,5-dimethylorsellinic acid-based (DMOA-based) meroterpenoids, including 10 new compounds, asperterpenes D-M (1-10), were obtained from Aspergillus terreus. The structures and absolute configurations of the new compounds were confirmed by extensive spectroscopy, single-crystal X-ray diffraction analysis, and experimental electronic circular dichroism (ECD) measurements. Compounds 2, 3, and 7 are the first 3,5-dimethylorsellinic acid-based meroterpenoids possessing a unique cis-fused A/B ring system. These new compounds were evaluated for their inhibitory activity against ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1). Compounds 2, 3, and 7, the first 3,5-dimethylorsellinic acid-based meroterpenoids possessing cis-fused A/B rings, exhibited significant inhibitory activities against BACE1 with IC50 values of 3.3, 5.9, and 31.7 µM, respectively.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Terpenos/isolamento & purificação , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Terpenos/química , Terpenos/farmacologia
16.
Fitoterapia ; 130: 134-139, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30165179

RESUMO

Terrusnolides A-D (1-4), four butenolides were isolated from an endophytic Aspergillus from Tripterygium wilfordii. The structures of 1-4 were established by comprehensive spectroscopic analyses and electronic circular dichroism (ECD) calculation. It is interesting that 1 was a butenolide derived by a triple decarboxylation, while 2-4 were the metabolites with 4-benzyl-3-phenyl-5H-furan-2-one motif possessing an isopentene group fused to the benzene ring. In vitro anti-inflammatory effects of these isolates were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. 1-4 exhibited excellent inhibitory effects on the production of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) in LPS-induced macrophages, comparable with the positive control (indomethacin). Those results indicated that, terrusnolides A-D might serve as new potential natural remedies for the treatment of inflammation.


Assuntos
4-Butirolactona/análogos & derivados , Anti-Inflamatórios/farmacologia , Aspergillus/química , Tripterygium/microbiologia , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , China , Endófitos/química , Interleucina-1beta/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Raízes de Plantas/microbiologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
17.
Curr Med Sci ; 38(1): 11-18, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30074146

RESUMO

Kinsenoside is a main active component isolated from plants of the genus Anoectochilus, and exhibits many biological activities and pharmacological effects, including hepatoprotective, anti-hyperglycemic, anti-hyperliposis, anti-inflammatory, vascular protective and anti-osteoporosis effects and so on, which is contributing to its promising potency in disease treatments. This review aims to recapitulate the pharmacological functions of kinsenoside, as well as its source, extraction, identification, quantitative analysis, pharmacokinetics, synthesis and patent information. The data reported in this work can confirm the therapeutic potential of kinsenoside and provide useful information for further new drug development.


Assuntos
4-Butirolactona/análogos & derivados , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/farmacocinética , Hipoglicemiantes/farmacologia , Monossacarídeos/farmacologia , Orchidaceae/química , 4-Butirolactona/química , 4-Butirolactona/farmacocinética , 4-Butirolactona/farmacologia , Animais , Conservadores da Densidade Óssea/química , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Fígado/efeitos dos fármacos , Monossacarídeos/química , Monossacarídeos/farmacocinética
18.
Bioorg Chem ; 80: 525-530, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30014920

RESUMO

Three new compounds, including a prenylated tryptophan derivative, luteoride E (1), a butenolide derivative, versicolactone G (2), and a linear aliphatic alcohol, (3E,7E)-4,8-dimethyl-undecane-3,7-diene-1,11-diol (3), together with nine known compounds (4-12), were isolated and identified from a coral-associated fungus Aspergillus terreus. Their structures were elucidated by HRESIMS, one- and two-dimensional NMR analysis, and the absolute configuration of 2 was determined by comparison of its electronic circular dichroism (ECD) spectrum with the literature. Structurally, compound 1 featured an unusual (E)-oxime group, which occurred rarely in natural products. Compounds 1-3 were evaluated for the α-glucosidase inhibitory activity, and compound 2 showed potent inhibitory potency with IC50 value of 104.8 ±â€¯9.5 µM, which was lower than the positive control acarbose (IC50 = 154.7 ±â€¯8.1 µM). Additionally, all the isolated compounds were evaluated for the anti-inflammatory activity against NO production, and compounds 1-3, 5-7, and 10 showed significant inhibitory potency with IC50 values ranging from 5.48 to 29.34 µM.


Assuntos
Antozoários/microbiologia , Anti-Inflamatórios/química , Aspergillus/química , Produtos Biológicos/química , Inibidores de Glicosídeo Hidrolases/química , 4-Butirolactona/análogos & derivados , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Aspergillus/metabolismo , Bactérias/efeitos dos fármacos , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Óxido Nítrico/antagonistas & inibidores , Células RAW 264.7 , Saccharomyces cerevisiae/enzimologia , Metabolismo Secundário , Sesquiterpenos
19.
J Org Chem ; 83(15): 8483-8492, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-30016097

RESUMO

Asperversiamides A-H (1-8), eight linearly fused prenylated indole alkaloids featuring an unusual pyrano[3,2- f]indole unit, were isolated from the marine-derived fungus Aspergillus versicolor. The structures and absolute configurations of these compounds were elucidated by extensive spectroscopic analyses, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and optical rotation (OR) calculations. The relative configuration of C-21 of iso-notoamide B was herein revised, and a new methodology for preliminarily determining if the relative configuration of the bicyclo[2.2.2]diazaoctane moiety of a spiro-bicyclo[2.2.2]diazaoctane-type indole alkaloid is syn or anti was developed. The anti-inflammatory activities of the isolated compounds were all tested, and of these compounds, 7 exhibited a potent inhibitory effect against iNOS with an IC50 value of 5.39 µM.


Assuntos
Organismos Aquáticos/microbiologia , Aspergillus/química , Alcaloides Indólicos/química , Prenilação , Modelos Moleculares , Conformação Molecular
20.
Mar Drugs ; 16(6)2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29882867

RESUMO

Asperversins A (1) and B (2), two novel meroterpenoids featuring an uncommon 5/6/6/6 ring system, along with five new analogues (3⁻7) and a known compound asperdemin (8), were obtained from the marine-derived fungus Aspergillus versicolor. Their structures and absolute configurations were confirmed by extensive spectroscopic analyses, single-crystal X-ray diffraction studies, and electronic circular dichroism (ECD) calculation. All new compounds were tested for their acetylcholinesterase enzyme (AChE) inhibitory activities and cytotoxic activities, of which compound 7 displayed moderate inhibitory activity against the AChE with an IC50 value of 13.6 μM.


Assuntos
Organismos Aquáticos/metabolismo , Aspergillus/metabolismo , Inibidores da Colinesterase/química , Terpenos/química , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Dicroísmo Circular , Cristalografia por Raios X , Concentração Inibidora 50 , Estrutura Molecular , Análise Espectral , Terpenos/isolamento & purificação , Terpenos/farmacologia
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