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1.
Phytochemistry ; 170: 112198, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31765875

RESUMO

Fungal endophytes from plants are an important source for discovery of novel bioactive natural products. In this study, five undescribed harziane diterpenoids with a 4/7/5/6 tetracyclic scaffold, harzianols F‒J and three known derivatives, were obtained from the liquid fermentation of an endophytic fungus Trichoderma atroviride B7, which was isolated from the healthy flower of a Lamiaceae plant Colquhounia coccinea var. mollis. Their structures were elucidated by comprehensive spectroscopic analyses and X-ray crystallographic diffraction in the case of harzianol F. Harzianol I exhibited significant antibacterial effect against the growth of Staphylococcus aureus (EC50 = 7.7 ± 0.8 µg/mL), Bacillus subtilis (EC50 = 7.7 ± 1.0 µg/mL), and Micrococcus luteus (EC50 = 9.9 ± 1.5 µg/mL). Meanwhile, cytotoxic activity of harzianol I against three cancer cell lines was also observed. A plausible biosynthetic pathway for harziane diterpenoids was proposed.

2.
Org Lett ; 22(1): 257-260, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31860319

RESUMO

Dactylicapnosines A (1) and B (2), two reconstructed aporphines with unprecedent five-membered carbon ring D, were isolated from Dactylicapnos scandens, in which dactylicapnosine A showed potent anti-inflammatory bioactivity in vitro. Inspired by its biosynthetic pathway, the total synthesis of dactylicapnosine A via 10 steps has been achieved and afforded enough material to prove its significant anti-inflammatory effect in vivo.

3.
Chin J Nat Med ; 17(12): 970-981, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31882053

RESUMO

Nineteen preschisanartane-type schinortriterpenoids (SNTs), among which eleven ones were previously undescribed, were isolated from two Schisandra species, S. sphaerandra and S. rubriflora. Their structures were determined using 1D and 2D NMR spectroscopic analyses, NMR data comparison, quantum chemical calculation of NMR parameters, electronic circular dichroism (ECD), X-ray single crystal diffraction, and chemical derivation. Furthermore, structural re-examination of a few previously reported preschisanartane-type SNTs led to the structural revision of preschisanartanin J. Besides, it is suggested that the reported structures of arisanlactone D and schilancidilactone W should be re-checked. Finally, a few isolated SNTs were found to possess neurite outgrowth-promoting activities, and protective activities against neural injuries.

4.
J Nat Prod ; 82(11): 2994-3001, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31674782

RESUMO

Flavipesines A and B (1 and 2) and asperchalasines E-H (3-6), two cytochalasans with an unusual ring system and four merocytochalasans possessing a 5/6/11/5/5/6 ring system, were isolated from Aspergillus flavipes, along with three related compounds (7-9). Their structures, including absolute configurations, were determined on the basis of data from HRESIMS, NMR, ECD, molecular modeling, and single-crystal X-ray diffraction. Flavipesines A and B (1 and 2) represent the first examples of cytochalasans possessing a 5/6/7/6 ring system with a C-18-O-C-21 bridge. Compounds 3, 7, and 9 show moderate inhibitory activities against isocitrate dehydrogenase 1 (IDH1). This is the first report on the IDH1 inhibitory activities of cytochalasans.

5.
Drug Des Devel Ther ; 13: 3021-3028, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692523

RESUMO

Background: Neolaxiflorin B is derived from ent-kaurane like laxiflorin J and eriocalyxin B with a relatively low potency as an antitumor agent. During preliminary structure-activity relationship studies, the α,ß-unsaturated ketone (enone) system is an important active group. Methods: Seven neolaxiflorin B derivatives containing α,ß-unsaturated ketone moieties were synthesized. In vitro, activity was evaluated against three human tumor cell lines and a rat myogenic cell line (HepG2, NSCLC-H292, SNU-1040, and L6, respectively) by MTT assay. Results: Compound 15 appeared a promising antitumor lead due to its cytotoxic potency and relatively high selectivity, with an SI value of 13.14. Flow cytometry analysis was conducted to show that NSCLC-H292 cells were blocked in the G0/G1 phase in the presence of compound 15, thus inhibiting the proliferation of tumor cells. Conclusion: This study has revealed that compound 15 is a promising antitumor lead due to the cytotoxic potencies and the high selectivity it displayed when compared to natural counterparts.

6.
J Nat Prod ; 82(12): 3221-3226, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31736307

RESUMO

Nine new alkaloids, (+)-1, (-)-1, 2, (+)-3, (-)-3, and 4-7, along with five known compounds (8-12), were obtained from the branches and leaves of Elaeocarpus angustifolius. The alkaloids were structurally characterized by NMR and MS data. The absolute configurations of (+)-1, (-)-1, (+)-3, and (-)-3 were determined by comparing their experimental and computed electronic circular dichroism spectra. (±)-8,9-Dehydroelaeocarpine (5), (±)-9-epielaeocarpine cis-N-oxide trifluoroacetate (6), and (±)-elaeocarpine trifluoroacetate (9) exerted weak inhibitory activities against butyrylcholinesterase with IC50 values of 39, 29, and 35 µM, respectively, while that of tacrine, the positive control, was 0.07 ± 0.01 µM. This is the first report of the cholinesterase inhibitory activities of Elaeocarpus alkaloids.

7.
Org Lett ; 21(20): 8353-8357, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31573213

RESUMO

Alterbrassinoids A-D (1-4), the first examples of fusicoccane-derived diterpenoid dimers furnished by forming an undescribed C-12-C-18' linkage, were isolated from modified cultures of Alternaria brassicicola. Compounds 1 and 2 represent unprecedented heterodimers, whereas 3 and 4 represent unprecedented homodimers, and 4 also features an undescribed anhydride motif. Their structures were assigned via spectroscopic methods, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Putative biosynthetic pathways and a bioactivity evaluation for 1-4 were discussed.

8.
J Nat Prod ; 82(10): 2925-2930, 2019 Oct 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.

9.
J Nat Prod ; 82(9): 2419-2429, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31503490

RESUMO

Eight new limonoids, toononoids A-H (1-8), eight new B-seco-29-norlimonoids, toonanoronoids A-H (9-16), and seven known analogues were obtained from the EtOAc extract of the twigs and leaves of Toona ciliata. Compounds 2, 4, 8, and 16 are rare lactam-bearing limonoids. Compounds 1, 14, and 15 possess an unusual γ-methoxybutenolide moiety at C-17, while compounds 9, 10, and 15 have a rare 3ß-hydroxy group. Their 2D structure and relative configurations were identified using spectroscopic data. The absolute configurations of 1, 9, 14, and 15 were established via X-ray diffraction crystallography or comparison of experimental and calculated ECD data. The cytotoxicity of the compounds was assessed toward five human tumor cell lines, and their anti-inflammatory activity was assessed based on NO production using LPS-stimulated RAW264.7 macrophages. Compounds 11 and 12 exerted inhibition toward two tumor cell lines (MCF-7, SW-480) with IC50 values between 2.1 and 3.7 µM, while 18-22 inhibited the proliferation of HL-60, MCF-7, and SW-480 cells (IC50 0.6-4.0 µM). Only compound 4 exhibited weak anti-inflammatory activity with an IC50 value of 28.3 µM.

10.
Org Lett ; 21(16): 6499-6503, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31343888

RESUMO

Here we provide an unprecedented biofactory where fluorescent dye-like complex xanthenes could be produced in an engineered Escherichia coli. Feeding the strain with toluquinol or hydroquinones resulted in production of novel "unnatural" natural products including four arthrocolins embedded with indolyltriphenyl quaternary carbons. Arthrocolins A-C potently inhibited various human cancer cell lines including paclitaxel-resistant cell line A549/Taxol and methicillin-resistant Staphylococcus aureus and immensely restored the sensitivity of intractable fluconazole-resistant human pathogen Candida albicans to fluconazole.

11.
Phytochemistry ; 166: 112065, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31362147

RESUMO

Ten undescribed neo-clerodane diterpenoids, named hispanins A-J, together with six known ones, were isolated from the aerial parts of Salvia hispanica L. Their structures were established by extensive spectroscopic analysis. The absolute configurations of the undescribed compounds were determined by the ECD data and single crystal X-ray diffraction analysis. Hispanins B and C represented the first neo-clerodane diterpenoids with a unique oxygen bridge between C-19 and C-20. All isolated compounds were evaluated for their protective effects against H2O2-induced cardiomyocyte injury. Five of these compounds showed significant cardioprotective effects.


Assuntos
Cardiotônicos/química , Cardiotônicos/farmacologia , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/farmacologia , Componentes Aéreos da Planta/química , Salvia/química , Animais , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos
12.
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
13.
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
14.
Org Lett ; 21(13): 5091-5095, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31247789

RESUMO

Emeriones A-C (1-3), three highly methylated polyketides with bicyclo[4.2.0]octene and 3,6-dioxabicyclo[3.1.0]hexane functionalities, were isolated from Emericella nidulans. An additional peroxide bridge in compound 3 led to the construction of an unexpected 7,8-dioxatricyclo[4.2.2.02,5]decene scaffold. The structures of 1-3 were elucidated by comprehensive spectroscopic techniques, and their absolute configurations were confirmed by single-crystal X-ray crystallographic analyses and ECD calculations. Compound 1 shows weak inhibitory effects on NO production in LPS-induced RAW264.7 cells.

15.
Molecules ; 24(12)2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31212847

RESUMO

Four new triterpenoids, 3ß,12ß,16ß,21ß,22-pentahydroxyhopane (1), 12ß,16ß,21ß,22-tetrahydroxyhopan-3-one (2), 3-oxo-olean-12-ene-28,30-dioic acid (3), and 3ß-hydroxyoleana-11,13(18)-diene-28,30-dioic acid 30-methyl ester (4); 21 new triterpenoid saponins, glinusopposides A-U (5-25); and 12 known compounds (26-37) were isolated from the whole plants of Glinus oppositifolius. The structures of the new compounds were elucidated based on the analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and mass spectrometry (MS) data. All compounds from the plants were measured for antifungal activities against Microsporum gypseum and Trichophyton rubrum. Glinusopposide B (6), glinusopposide Q (21), glinusopposide T (24), and glinusopposide U (25) showed strong inhibitory activities against M. gypseum (MIC50 7.1, 6.7, 6.8, and 11.1 µM, respectively) and T. rubrum (MIC50 14.3, 13.4, 11.9, and 13.0 µM, respectively). For those active compounds with an oleanane skeleton, glycosylation (21-26) or oxidation (3) of 3-OH was helpful in increasing the activity; replacement of the 30-methyl group (29) by a carboxymethyl group (26) enhanced the activity; the presence of 11,13(18) double bonds (20) decreased the activity.


Assuntos
Antifúngicos/farmacologia , Glicosídeos/farmacologia , Microsporum/efeitos dos fármacos , Molluginaceae/química , Trichophyton/efeitos dos fármacos , Triterpenos/farmacologia , Antifúngicos/química , Glicosídeos/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Triterpenos/química
16.
J Org Chem ; 84(9): 5483-5491, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-30997804

RESUMO

Amiaspochalasins A-H (1-8), eight undescribed aspochalasins, and trichalasin D (9), a known analogue, were isolated from the solid culture of Aspergillus micronesiensis. Compounds 1-9 are aspochalasins with a C-21 ester carbonyl, and their structures were determined by spectroscopic data, X-ray crystallographic analyses, electronic circular dichroism calculations, and chemical methods. The CH3-25 in compound 1 is located at C-16 rather than C-14 in the previously reported aspochalasins, endowing 1 with an unexpected carbon skeleton. Compounds 2 and 3 are the first examples of aspochalasins with an unprecedented 5/6/6/8 tetracyclic ring system. Compounds 4 and 5 are diastereomers of aspochalasins I and J, respectively. Compounds 6 and 7 are the first aspochalasins featuring a long open-chain system, and their absolute configurations were discussed by comparing the NMR data of the hydrolysis and methyl esterification products of 4 and 5. Compound 8 is an isomeride of 9. The cytotoxic and antimicrobial effects of 1-9 were tested.

17.
Org Lett ; 21(7): 2290-2293, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30865467

RESUMO

Niduterpenoids A (1) and B (2), two sesterterpenoids with a highly congested hexacyclic 5/5/5/5/3/5 carbon skeleton but no unsaturated functional group, were isolated from Aspergillus nidulans. Their structures were determined by a combination of spectroscopic data and single-crystal X-ray diffraction analyses. Compounds 1 and 2 present the first examples of sesterterpenoids with a hexacyclic carbon ring system. Compound 1 showed no cytotoxicity but abolished 17-estradiol-induced cell proliferation (IC50 = 11.42 ± 0.85 µM).


Assuntos
Aspergillus nidulans/química , Carbono/química , Sesterterpenos/química , Cristalografia por Raios X , Estrutura Molecular , Sesterterpenos/isolamento & purificação , Análise Espectral
18.
Fitoterapia ; 134: 158-164, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30825576

RESUMO

Four new ent-abietane diterpenoids, isoforrethins A-D (1-4), were isolated from the aerial parts of Isodon forrestii var. forrestii by a variety of chromatographic techniques. Their structures were elucidated on the basis of spectroscopic data interpretation, single crystal X-ray diffraction, and quantum chemical calculation. All of these compounds were evaluated for their cytotoxicity against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and compound 4 showed significant inhibitory activities against SMMC-7721, A-549, MCF-7, and SW-480.


Assuntos
/farmacologia , Isodon/química , /isolamento & purificação , Antineoplásicos Fitogênicos , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química
19.
J Nat Prod ; 82(4): 735-740, 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-30767530

RESUMO

The enantiomers (+)- and (-)-alternarilactone A (1), the first examples of dibenzo-α-pyrones bearing a diepoxy-cage-like moiety, were isolated from the endophytic fungus Alternaria sp. hh930. The deficiency in 1H-1H COSY and HMBC correlations caused by the highly oxidized caged system of 1 and the deceptive and ambiguous signals such as "W" couplings in NMR data increased the risk of structure misassignment of 1. By performing a quantum chemical calculation of the NMR chemical shifts together with a DP4+ probability analysis and single-crystal X-ray crystallographic experiment, their structures were unambiguously determined, and their absolute configurations were determined by ECD calculations.

20.
Org Lett ; 21(3): 771-775, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640477

RESUMO

Isopenicins A-C (1-3), three novel meroterpenoids possessing two types of unprecedented terpenoid-polyketide hybrid skeletons, were isolated from the cultures of Penicillium sp. sh18. Their structures were determined through synergetic use of extensive spectroscopic analysis, quantum-chemical calculation with ANN-PRA analysis, and X-ray crystallographic analysis. Additionally, the inhibitory activities of these compounds on the Wnt/ß-catenin signaling pathway were evaluated, and 1 was identified as a potent inhibitor of the Wnt signaling pathway.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Endófitos/química , Penicillium/química , Terpenos/química , Terpenos/farmacologia , Células HEK293 , Humanos , Modelos Moleculares , Conformação Molecular , Via de Sinalização Wnt/efeitos dos fármacos
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