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1.
Prog Chem Org Nat Prod ; 111: 81-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32114663

RESUMO

Marine-derived fungi play an important role in the search for structurally unique secondary metabolites, some of which show promising pharmacological activities that make them useful leads for drug discovery. Marine natural product research in China in general has made enormous progress in the last two decades as described in this chapter on fungal metabolites. This contribution covers 613 new natural products reported from 2001 to 2017 from marine-derived fungi obtained from algae, sponges, corals, and other marine organisms from Chinese waters. The genera Aspergillus (170 new natural products, 28%) and Penicillium (70 new natural products, 11%) were the main fungal producers of new natural products during the time period covered, whereas sponges (184 new natural products, 30%) were the most abundant source of new natural products, followed by corals (154 new natural products, 25%) and algae (130 new natural products, 21%). Close to 40% of all natural products covered in this contribution displayed various bioactivities. The major bioactivities reported were cytotoxicity against different cancer cell lines, antimicrobial (mainly antibacterial) activity, and antiviral activity, which accounted for 13%, 9%, and 3% of all natural products reported. In terms of structural classes, polyketides (188 new natural products, 31%) play a dominant role, and if prenylated polyketides and nitrogen-containing polyketides (included in meroterpenes and alkaloids in this contribution) are taken into account, their total number even exceeds 50%. Nitrogen-containing compounds including peptides (65 new natural products, 10%) and alkaloids (103 new natural products, 17%) are the second largest group.


Assuntos
Produtos Biológicos/farmacologia , Fungos/química , Policetídeos/farmacologia , Animais , Antozoários/microbiologia , Anti-Infecciosos , Antineoplásicos , Organismos Aquáticos/microbiologia , Aspergillus/química , Produtos Biológicos/química , China , Penicillium/química , Policetídeos/química , Poríferos/microbiologia , Metabolismo Secundário
2.
Phytochemistry ; 170: 112191, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31731236

RESUMO

Seven undescribed polyketides javanicols A-E, 5-epi-citreoviridin and 5-epi-isocitreoviridin, together with five known compounds, were isolated from the endolichenic fungus Eupenicillium javanicum. The structures of these polyketides were determined by means of extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations and gauge-independent atomic orbital (GIAO) NMR shift calculations. These compounds were evaluated for potential anti-inflammatory activity against LPS-activated RAW 264.7 cells. Javanicol E and (+)-terrein displayed moderate inhibitory effects on NO production, with IC50 values of 17.00 and 13.46 µM, respectively.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Eupenicillium/química , Óxido Nítrico/antagonistas & inibidores , Policetídeos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Compostos Fitoquímicos , Policetídeos/química , Policetídeos/isolamento & purificação , Células RAW 264.7
3.
J Agric Food Chem ; 67(51): 14102-14109, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31790231

RESUMO

Herbicidal activity-guided isolation from the fermentation extract of Penicillium viridicatum had obtained two herbicidal series of polyketides (1-7) and diketopiperazine derivatives (8-11), especially including three novel polyketides (1-3). The structures and absolute configurations of new polyketides 1-3 were elucidated by extensive spectroscopic analyses, as well as comparisons between measured and calculated ECD spectra. Novel polyketides 1-3 and known 4, all bearing the heptaketide skeleton with a trans-fused decalin ring of 8-CH3 substitution, could significantly inhibit the radicle growth of Echinochloa crusgalli seedlings with a dose-dependent relationship. Especially at the concentration of 10 µg/mL, 1-4 exhibited the inhibition rates with 81.5% ± 2.0, 76.4% ± 0.8, 79.6% ± 1.1, and 80.0 ± 1.8%, respectively, even better than the commonly used synthetic herbicide of acetochlor with 76.1 ± 1.4%. Further greenhouse bioassay revealed that 4 showed pre-emergence herbicidal activity against E. crusgalli with the fresh-weight inhibition rate of 74.1% at a dosage of 400 g ai/ha, also better than acetochlor, while the other isolated metabolites (5-11) exhibited moderate herbicidal activities. The structure-activity differences of isolated polyketides indicated that the heptaketide skeleton, characterized by a trans-fused decalin ring with 8-CH3 substitution, should be the key factor of their herbicidal activities, which could give new insights for the bioherbicide developments.


Assuntos
Dicetopiperazinas/farmacologia , Herbicidas/farmacologia , Penicillium/química , Policetídeos/farmacologia , Dicetopiperazinas/metabolismo , Echinochloa/efeitos dos fármacos , Echinochloa/crescimento & desenvolvimento , Herbicidas/metabolismo , Estrutura Molecular , Penicillium/metabolismo , Policetídeos/metabolismo
4.
Mar Drugs ; 17(10)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614563

RESUMO

Four new compounds were isolated from the Vietnamese marine sediment-derived fungus Aspergillus flocculosus, one aspyrone-related polyketide aspilactonol G (2), one meroterpenoid 12-epi-aspertetranone D (4), two drimane derivatives (7,9), together with five known metabolites (1,3,5,6,8,10). The structures of compounds 1-10 were established by NMR and MS techniques. The absolute stereoconfigurations of compounds 1 and 2 were determined by a modified Mosher's method. The absolute configurations of compounds 4 and 7 were established by a combination of analysis of ROESY data and coupling constants as well as biogenetic considerations. Compounds 7 and 8 exhibited cytotoxic activity toward human prostate cancer 22Rv1, human breast cancer MCF-7, and murine neuroblastoma Neuro-2a cells.


Assuntos
Antineoplásicos/farmacologia , Organismos Aquáticos/metabolismo , Aspergillus/metabolismo , Produtos Biológicos/farmacologia , Fungos/metabolismo , Animais , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Sedimentos Geológicos/microbiologia , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética/métodos , Biologia Marinha/métodos , Camundongos , Policetídeos/farmacologia , Sesquiterpenos/farmacologia
5.
Fitoterapia ; 139: 104369, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31626911

RESUMO

Five new polyketides, colletotric B (2), 3-hydroxy-5-methoxy-2,4,6-trimethylbenzoic acid (3), colletotric C (4), chaetochromone D (6) and 8-hydroxy-pregaliellalactone B (9), together with four known analogues (1, 5 and 7-8) were isolated from the mangrove endophytic fungus Phoma sp. SYSU-SK-7. Their structures were elucidated by analysis of extensive spectroscopic data and mass spectrometric data. Compounds 1-2 showed strong antimicrobial activity against the P. aeruginosa, MRSA and C. albicans with the MIC values in the range of 1.67-6.28 µg/ml. Furthermore, Compounds 1-5 also exhibited significant α-glucosidase inhibitory activity with the IC50 values in the range of 36.2-90.6 µM. Compound 7 was found to inhibited radical scavenging activity against DPPH with the EC50 value of 11.8 µM.


Assuntos
Anti-Infecciosos/farmacologia , Ascomicetos/química , Depuradores de Radicais Livres/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Policetídeos/farmacologia , Rhizophoraceae/microbiologia , Anti-Infecciosos/isolamento & purificação , China , Endófitos/química , Depuradores de Radicais Livres/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Policetídeos/isolamento & purificação
6.
Molecules ; 24(18)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533358

RESUMO

Drug-like molecules are known to contain many different building blocks with great potential as pharmacophores for drug discovery. The continued search for unique scaffolds in our laboratory led to the isolation of a novel Ghanaian soil bacterium, Streptomyces sp. MA37. This strain produces many bioactive molecules, most of which belong to carbazoles, pyrrolizidines, and fluorinated metabolites. Further probing of the metabolites of MA37 has led to the discovery of a new naphthacene-type aromatic natural product, which we have named accramycin A 1. This molecule was isolated using an HPLC-photodiode array (PDA) guided isolation process and MS/MS molecular networking. The structure of 1 was characterized by detailed analysis of LC-MS, UV, 1D, and 2D NMR data. Preliminary studies on the antibacterial properties of 1 using Group B Streptococcus (GBS) produced a minimum inhibitory concentration (MIC) of 27 µg/mL. This represents the first report of such bioactivity amongst the naphthacene-type aromatic polyketides, and also suggests the possibility for the further development of potent molecules against GBS based on the accramycin scaffold. A putative acc biosynthetic pathway for accramycin, featuring a tridecaketide-specific type II polyketide synthase, was proposed.


Assuntos
Policetídeos/química , Policetídeos/isolamento & purificação , Microbiologia do Solo , Streptomyces/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Vias Biossintéticas , Genes Bacterianos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Família Multigênica , Policetídeos/metabolismo , Policetídeos/farmacologia , Streptomyces/genética , Streptomyces/metabolismo
7.
Fitoterapia ; 137: 104282, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381956

RESUMO

Four new polyketides, alternatains A-D (1-4), along with 17 known compounds (5-21) were obtained from the solid substrate fermentation cultures of Alternaria alternata MT-47, an endophytic fungus isolated from the medicinal plant of Huperzia serrata. Their structures were elucidated by extensive spectroscopic and spectrometric techniques (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) method. Compounds 4, 6, 15, and 21 exhibited inhibitory activities on ATP release of thrombin-activated platelets with IC50 values in the range of 18.2-68.8 µM.


Assuntos
Alternaria/química , Anticoagulantes/farmacologia , Plaquetas/efeitos dos fármacos , Huperzia/microbiologia , Policetídeos/farmacologia , Acetilcolinesterase , Trifosfato de Adenosina , Anticoagulantes/isolamento & purificação , Butirilcolinesterase , China , Inibidores da Colinesterase , Endófitos/química , Humanos , Estrutura Molecular , Plantas Medicinais/microbiologia , Policetídeos/isolamento & purificação
8.
Molecules ; 24(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443573

RESUMO

Two new chromone-derived polyketides phaseolorins, G and H (1 and 2), and one new anthraquinone derivative, phaseolorin I (3), together with three known compounds (4-6), were isolated from the deep-sea sediment-derived fungus Diaporthe phaseolorum FS431. The structures of the new compounds were determined by comprehensive analysis of their spectroscopic data, and the absolute configuration of 1 was established by quantum chemical calculations of electron capture detection (ECD). All the isolated compounds (1-6) were tested for their in vitro cytotoxic activities against four human tumor cell lines, of which compound 4 exhibited significant effect against MCF-7, HepG-2, and A549 tumor cell lines with IC50 values of 2.60, 2.55, and 4.64 µM, respectively.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Microbiologia Ambiental , Fungos/química , Sedimentos Geológicos/microbiologia , Policetídeos/química , Policetídeos/farmacologia , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Oceanos e Mares , Policetídeos/isolamento & purificação , Relação Estrutura-Atividade
9.
Mar Drugs ; 17(7)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284448

RESUMO

The sponge-derived fungus Penicillium sp. SCSIO41015 cultured on solid rice medium yielded twenty-one compounds (1-21), including two new alkaloids (1 and 2) and one new pyrone derivative (3). Their structures were elucidated by analysis of 1D/2D NMR data and HR-ESI-MS. Their absolute configurations were established by single-crystal X-ray diffraction analysis and comparison of the experimental with reported specific rotation values. Compound 16 exhibited selective cytotoxic activity against the human gastric cancer cells MGC803, with IC50 value of 5.19 µM. Compounds 9 and 18 showed weak antibacterial activity against Staphylococcus aureus and Acinetobacter baumannii, respectively, both with MIC values of 57 µg/mL. Furthermore, compound 16 displayed potent antibacterial activity against S. aureus with an MIC value of 3.75 µg/mL.


Assuntos
Alcaloides/química , Organismos Aquáticos/química , Fungos/química , Penicillium/química , Policetídeos/química , Poríferos/microbiologia , Células A549 , Alcaloides/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Testes de Sensibilidade Microbiana/métodos , Policetídeos/farmacologia , Pironas/química , Pironas/farmacologia
10.
Molecules ; 24(14)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31336683

RESUMO

Four new compounds, including two new polyketides, heterocornols M and N (1, 2), and a pair of epimers, heterocornols O and P (3, 4), were isolated from the fermentation broth of the marine sponge-derived fungus Pestalotiopsis heterocornis XWS03F09, together with three known compounds (5-7). The new chemical structures were established on the basis of a spectroscopic analysis, optical rotation, experimental and calculated electronic circular dichroism (ECD). All of the compounds (1-7) were evaluated for their cytotoxic activities, and heterocornols M-P (1-4) exhibited cytotoxicities against four human cancer cell lines with IC50 values of 20.4-94.2 µM.


Assuntos
Organismos Aquáticos/microbiologia , Ascomicetos/química , Produtos Biológicos/farmacologia , Policetídeos/farmacologia , Poríferos/microbiologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Estrutura Molecular , Policetídeos/química , Policetídeos/isolamento & purificação , Análise Espectral
11.
Mar Drugs ; 17(7)2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31336899

RESUMO

Six new polyketides, including one coumarin (1), two isocoumarins (2 and 3), dihydroradicinin (4), and two benzofuranone derivatives (7 and 8), together with seven known analogues (5-6 and 9-13) were isolated from the culture of the mangrove endophytic fungus Epicoccum nigrum SCNU-F0002. The structures were elucidated on the interpretation of spectroscopic data. The absolute configuration of Compounds 2 and 3 were determined by comparison of their ECD spectra with the data of their analogue dihydroisocoumarins described in the literature. The absolute configuration of 4 was determined by single-crystal X-ray diffraction. All the compounds were screened for their antioxidant, antibacterial, anti-phytopathogenic fungi and cytotoxic activities. Using a DPPH radical-scavenging assay, Compounds 10-13 showed potent antioxidant activity with IC50 values of 13.6, 12.1, 18.1, and 11.7 µg/mL, respectively. In addition, Compounds 6 and 7 showed antibacterial effects against Bacillus subtilis (ATCC 6538), Escherichia coli (ATCC 8739), and Staphylococcus aureus (ATCC 6538), with MIC values in the range of 25-50 µg/mL.


Assuntos
Organismos Aquáticos/química , Ascomicetos/química , Endófitos/química , Policetídeos/farmacologia , Acanthaceae/microbiologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Linhagem Celular Tumoral , Escherichia coli/efeitos dos fármacos , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Policetídeos/química , Policetídeos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Áreas Alagadas
12.
Mar Drugs ; 17(7)2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31252576

RESUMO

Due to the unique biodiversity and the physical-chemical properties of their environment, marine microorganisms have evolved defense and signaling compounds that often have no equivalent in terrestrial habitats. The aim of this study was to screen extracts of the dinoflagellate Amphidinium carterae for possible bioactivities (i.e., anticancer, anti-inflammatory, anti-diabetes, antibacterial and antifungal properties) and identify bioactive compounds. Anticancer activity was evaluated on human lung adenocarcinoma (A549), human skin melanoma (A2058), human hepatocellular carcinoma (HepG2), human breast adenocarcinoma (MCF7) and human pancreas carcinoma (MiaPaca-2) cell lines. Antimicrobial activities were evaluated against Gram-positive bacteria (Staphylococcus aureus MRSA and MSSA), Gram-negative bacteria (i.e., Escherichia coli and Klebsiella pneumoniae), Mycobacterium tuberculosis and the fungus Aspergillus fumigatus. The results indicated moderate biological activities against all the cancer cells lines and microorganisms tested. Bioassay-guided fractionation assisted by HRMS analysis allowed the detection of one new and two known amphidinols that are potentially responsible for the antifungal and cytotoxic activities observed. Further isolation, purification and structural elucidation led to a new amphidinol, named amphidinol 22. The planar structure of the new compound was determined by analysis of its HRMS and 1D and 2D NMR spectra. Its biological activity was evaluated, and it displayed both anticancer and antifungal activities.


Assuntos
Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Dinoflagelados/química , Policetídeos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Aspergillus fumigatus/efeitos dos fármacos , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Policetídeos/química , Policetídeos/isolamento & purificação , Relação Estrutura-Atividade
13.
PLoS One ; 14(6): e0218190, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31181122

RESUMO

Diaphorin is a polyketide produced by Candidatus Profftella armatura (Betaproteobacteria), an organelle-like defensive symbiont harbored by a plant sap-sucking insect, Asian citrus psyllid Diaphorina citri (Hemiptera: Liviidae). Diaphorin belongs to the pederin family, a group of compounds that share much of their core structure with that of pederin, which is characterized by two dihydropyran rings bridged by an N-acyl aminal. Most members of this family have potent antitumor activity, making them promising anticancer drug candidates. The present study assessed the therapeutic potential of diaphorin for its antitumor activity against 39 human cancer cell lines including those from breast, brain, colon, lung, skin, ovary, kidney, stomach, and prostate. The results showed that diaphorin had inhibitory activity against all 39 cancer cell lines tested. The GI50, TGI, and LC50 values ranged from 0.28 µM- 2.4 µM, 1.6 µM -11 µM, and 7.5 µM-> 100 µM, respectively. These values are among the highest in the pederin family, indicating that the anticancer activity of diaphorin is milder than those of other pederin congeners. The inhibitory effects of diaphorin significantly differed among the distinct cancer types. The maximum difference was about 10-fold, which was similar to those of most other pederin congeners.


Assuntos
Betaproteobacteria/metabolismo , Hemípteros/química , Policetídeos/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Hemípteros/microbiologia , Humanos , Concentração Inibidora 50 , Policetídeos/farmacologia , Simbiose
14.
World J Microbiol Biotechnol ; 35(6): 92, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31187317

RESUMO

Polyketides and peptides obtained from actinobacteria are important therapeutic compounds which include front line antibiotics and anticancer drugs. Many screening programs are directed towards isolation of bioactive compounds from these organisms but the chances of finding novel antimicrobial leads among common actinobacteria are fast dwindling. As a result, the focus has shifted to the members of less exploited genera of rare actinobacteria. Three isolates, MMS8, MMS16 and KCR3 found to be potent polyketide and peptide producers were identified by 16S rRNA gene sequencing and their sequences deposited in the GenBank under the accession numbers MG407702, MG372012 and MG430204 respectively. MMS8 identified as Micromonospora auratinigra, yielded one potent compound determined to be chloroanthraquinone with an minimum inhibitory concentration (MIC) of 8 µg/ml against Bacillus subtilis and an IC50 value of 10 µg/ml and 4 µg/ml against HeLa and IMR cell lines respectively. This is the first report of the production of chloroanthraquinone by M. auratinigra. MMS16, identified as a member of the family Micromonosporaceae, yielded a potent compound MMS16B analyzed to be a novel bafilomycin analogue. The MIC of the compound was found to be 7 µg/ml against B.subtilis and IC50 value against HeLa and IMR was observed to be 9 µg/ml and 14 µg/ml respectively. MMS16B was also found to exhibit anti-quorum sensing (AQS) activity at sublethal concentrations. KCR3 identified as Kocuria kristinae yielded a novel antimicrobial peptide with antibacterial, antifungal and AQS activity. To the best of our knowledge, no antimicrobial activity has ever been reported from K. kristinae.


Assuntos
Actinobacteria/metabolismo , Peptídeos/metabolismo , Policetídeos/metabolismo , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Animais , Antibacterianos/metabolismo , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Antineoplásicos/metabolismo , Bacillus subtilis/efeitos dos fármacos , Linhagem Celular , Testes de Sensibilidade Microbiana , Micromonospora/genética , Micromonospora/isolamento & purificação , Micromonospora/metabolismo , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Policetídeos/isolamento & purificação , Policetídeos/farmacologia , RNA Ribossômico 16S/genética
15.
Fitoterapia ; 137: 104187, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31153951

RESUMO

Four new compounds: diaporthichalasins A-C (1-3) and biatriosporin N (7), along with six known compounds (4-6 and 8-10) were separated from the culture of the fungus Diaporthe sp. GZU-1021. The absolute configurations of 1-3 were determined by quantum chemical calculations, X-ray diffraction, and spectroscopic analysis. The structure of 4 was analyzed by X-ray crystallography analysis for the first time. All of the isolates were evaluated on the production of nitric oxide in lipopolysaccharide-induced microglial cells (RAW 264.7 cells). Compounds 5-10 exhibited significant inhibitory effects against nitric oxide production with IC50 values from 1.94 to 16.5 µM than positive control (indomethacin, IC50 = 29.7 µM). This is the first time tetrahydroxanthone dimer (10), as a novel carbon skeleton possessing NO inhibitory activity, was reported.


Assuntos
Anti-Inflamatórios/farmacologia , Ascomicetos/química , Citocalasinas/farmacologia , Microglia/efeitos dos fármacos , Policetídeos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Braquiúros/microbiologia , China , Citocalasinas/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Policetídeos/isolamento & purificação , Células RAW 264.7
16.
Molecules ; 24(12)2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31208056

RESUMO

The strain Streptomyces osmaniensis CA-244599 isolated from the Comoros islands was submitted to liquid-state fermentation coupled to in situ solid-phase extraction with amberlite XAD-16 resin. Elution of the trapped compounds on the resin beads by ethyl acetate afforded seven metabolites, osmanicin (1), streptazolin (2), streptazone C (3), streptazone B1 (4), streptenol C (5), nocardamine (6) and desmethylenylnocardamine (7). Osmanicin (1) is a newly reported unusual scaffold combining streptazolin (2) and streptazone C (3) through a Diels-Alder type reaction. Experimental evidence excluded the spontaneous formation of 1 from 2 and 3. The isolated compounds were evaluated for their ability to inhibit elastase using normal human diploid fibroblasts. Compound 1 exhibited the most potent activity with an IC50 of 3.7 µM.


Assuntos
Alcaloides/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Elastase Pancreática/antagonistas & inibidores , Policetídeos/farmacologia , Streptomyces/química , Alcaloides/biossíntese , Alcaloides/química , Alcaloides/isolamento & purificação , Vias Biossintéticas , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fermentação , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Policetídeos/química , Policetídeos/isolamento & purificação , Policetídeos/metabolismo , RNA Ribossômico 16S/genética , Streptomyces/classificação , Streptomyces/genética
17.
Mar Drugs ; 17(5)2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31108946

RESUMO

Five new polyketides, namely, 5R-hydroxyrecifeiolide (1), 5S-hydroxyrecifeiolide (2), ent-cladospolide F (3), cladospolide G (4), and cladospolide H (5), along with two known compounds (6 and 7), were isolated from the endophytic fungal strain Cladosporium cladosporioides MA-299 that was obtained from the leaves of the mangrove plant Bruguiera gymnorrhiza. The structures of these compounds were established by extensive analysis of 1D/2D NMR data, mass spectrometric data, ECDs and optical rotations, and modified Mosher's method. The structures of 3 and 6 were confirmed by single-crystal X-ray diffraction analysis and this is the first time for reporting the crystal structures of these two compounds. All of the isolated compounds were examined for antimicrobial activities against human and aquatic bacteria and plant pathogenic fungi as well as enzymatic inhibitory activities against acetylcholinesterase. Compounds 1-4, 6, and 7 exhibited antimicrobial activity against some of the tested strains with MIC values ranging from 1.0 to 64 µg/mL, while 3 exhibited enzymatic inhibitory activity against acetylcholinesterase with the IC50 value of 40.26 µM.


Assuntos
Cladosporium/química , Policetídeos/química , Acetilcolinesterase/metabolismo , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Cristalografia por Raios X , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Fungos/efeitos dos fármacos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Policetídeos/isolamento & purificação , Policetídeos/farmacologia , Rhizophoraceae/microbiologia
18.
PLoS One ; 14(5): e0216319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31048920

RESUMO

The Asian citrus psyllid Diaphorina citri Kuwayama (Hemiptera: Sternorrhyncha: Psylloidea: Liviidae) is an important pest of citrus species worldwide because it transmits Candidatus Liberibacter spp. (Alphaproteobacteria), the causative agents of an incurable citrus disease known as huanglongbing or greening disease. Diaphorina citri possesses a vertically-transmitted intracellular symbiont, Candidatus Profftella armatura (Betaproteobacteria), which produces diaphorin, a polyketide that is significantly toxic to mammalian cells. Diaphorin is an analog of pederin, a defensive polyketide in the body fluid of Paederus rove beetles (Coleoptera: Staphylinidae) that deters predators. In the present study, as a first step to assess the possibility that diaphorin is toxic to biological control agents, we assayed diaphorin activities against insects and fungi. The target cells and organisms were (a) the Sf9 cell line derived from the fall armyworm moth Spodoptera frugiperda (Lepidoptera: Noctuidae), (b) the pea aphid Acyrthosiphon pisum (Hemiptera: Sternorrhyncha: Aphidoidea: Aphididae), a phloem sap-sucking insect that is closely related to psyllids, (c) the Asian lady beetle Harmonia axyridis (Coleoptera: Coccinellidae), one of the major predators of D. citri, and (d) the budding yeast Saccharomyces cerevisiae (Ascomycota: Saccharomycetes) as a model of fungal pathogens. For a comparison, we also evaluated pederin activities. The results of our analyses revealed the following: (1) Diaphorin and pederin are significantly toxic to the tested insects and yeast; (2) Their toxicities vary widely among the target cells and organisms; (3) Diaphorin is generally less toxic than pederin; (4) The toxicities of diaphorin and pederin are considerably different in the Sf9 insect cell line and S. cerevisiae, but similar in A. pisum and H. axyridis; and (5) The amount of diaphorin contained in D. citri is toxic to all of the tested cells and organisms, suggesting that this polyketide is potentially harmful for biological control agents.


Assuntos
Anti-Infecciosos , Betaproteobacteria/metabolismo , Citotoxinas , Hemípteros/microbiologia , Controle Biológico de Vetores , Policetídeos , Simbiose , Células A549 , Animais , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Citotoxinas/metabolismo , Citotoxinas/farmacologia , Células HCT116 , Humanos , Células MCF-7 , Células PC-3 , Policetídeos/metabolismo , Policetídeos/farmacologia
19.
Mar Drugs ; 17(4)2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30959907

RESUMO

Lymphangiogenesis is an important biological process associated with cancer metastasis. The development of new drugs that block lymphangiogenesis represents a promising therapeutic strategy. Marine fungus-derived compound phomaketide A, isolated from the fermented broth of Phoma sp. NTOU4195, has been reported to exhibit anti-angiogenic and anti-inflammatory effects. However, its anti-lymphangiogenic activity has not been clarified to date. In this study, we showed that phomaketide A inhibited cell growth, migration, and tube formation of lymphatic endothelial cells (LECs) without an evidence of cytotoxicity. Mechanistic investigations revealed that phomaketide A reduced LECs-induced lymphangiogenesis via vascular endothelial growth factor receptor-3 (VEGFR-3), protein kinase Cδ (PKCδ), and endothelial nitric oxide synthase (eNOS) signalings. Furthermore, human proteome array analysis indicated that phomaketide A significantly enhanced the protein levels of various protease inhibitors, including cystatin A, serpin B6, tissue factor pathway inhibitor (TFPI), and tissue inhibitor matrix metalloproteinase 1 (TIMP-1). Importantly, phomaketide A impeded tumor growth and lymphangiogenesis by decreasing the expression of LYVE-1, a specific marker for lymphatic vessels, in tumor xenograft animal model. These results suggest that phomaketide A may impair lymphangiogenesis by suppressing VEGFR-3, PKCδ, and eNOS signaling cascades, while simultaneously activating protease inhibitors in human LECs. We document for the first time that phomaketide A inhibits lymphangiogenesis both in vitro and in vivo, which suggests that this natural product could potentially treat cancer metastasis.


Assuntos
Inibidores da Angiogênese/farmacologia , Antinematódeos/farmacologia , Ascomicetos/química , Linfangiogênese/efeitos dos fármacos , Policetídeos/farmacologia , Células A549 , Inibidores da Angiogênese/isolamento & purificação , Inibidores da Angiogênese/uso terapêutico , Animais , Antinematódeos/isolamento & purificação , Antinematódeos/uso terapêutico , Organismos Aquáticos/química , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Metástase Linfática , Vasos Linfáticos/citologia , Masculino , Camundongos , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Óxido Nítrico Sintase Tipo III/metabolismo , Policetídeos/isolamento & purificação , Policetídeos/uso terapêutico , Proteína Quinase C-delta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Mar Drugs ; 17(4)2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31010150

RESUMO

Spirotetronates are actinomyces-derived polyketides that possess complex structures and exhibit potent and unexplored bioactivities. Due to their anticancer and antimicrobial properties, they have potential as drug hits and deserve further study. In particular, abyssomicin C and tetrocarcin A have shown significant promise against antibiotic-resistant S. aureus and tuberculosis, as well as for the treatment of various lymphomas and solid tumors. Improved synthetic routes to these compounds, particularly the class II spirotetronates, are needed to access sufficient quantities for structure optimization and clinical applications.


Assuntos
Aminoglicosídeos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Policetídeos/química , Compostos de Espiro/química , Aminoglicosídeos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Descoberta de Drogas , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Policetídeos/metabolismo , Policetídeos/farmacologia , Compostos de Espiro/metabolismo , Compostos de Espiro/farmacologia
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