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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.
Nat Commun ; 11(1): 80, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900404

RESUMO

To harness the synthetic power of modular polyketide synthases (PKSs), many aspects of their biochemistry must be elucidated. A robust platform to study these megadalton assembly lines has not yet been described. Here, we in vitro reconstitute the venemycin PKS, a short assembly line that generates an aromatic product. Incubating its polypeptides, VemG and VemH, with 3,5-dihydroxybenzoic acid, ATP, malonate, coenzyme A, and the malonyl-CoA ligase MatB, venemycin production can be monitored by HPLC and NMR. Multi-milligram quantities of venemycin are isolable from dialysis-based reactors without chromatography, and the enzymes can be recycled. Assembly line engineering is performed using pikromycin modules, with synthases designed using the updated module boundaries outperforming those using the traditional module boundaries by over an order of magnitude. Using combinations of VemG, VemH, and their engineered derivatives, as well as the alternate starter unit 3-hydroxybenzoic acid, a combinatorial library of six polyketide products is readily accessed.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Policetídeo Sintases/química , Policetídeo Sintases/genética , Streptomyces/enzimologia , Proteínas de Bactérias/metabolismo , Macrolídeos/química , Policetídeo Sintases/metabolismo , Policetídeos/química , Engenharia de Proteínas , Streptomyces/química , Streptomyces/genética , Especificidade por Substrato
3.
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
4.
Chem Commun (Camb) ; 55(79): 11956-11959, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31531455

RESUMO

Verucopeptin is an inhibitor of hypoxia-inducible factor 1 (HIF-1), which is a promising target for cancer chemotherapy. Here, we report the first total synthesis of verucopeptin via condensation of the depsipeptide core and the polyketide side chain unit including three branched methyl groups after the synthesis of each segment.


Assuntos
Depsipeptídeos/síntese química , Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Alquinos/química , Depsipeptídeos/química , Imidazóis/química , Estrutura Molecular , Policetídeos/química
5.
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
6.
Nat Commun ; 10(1): 3918, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477708

RESUMO

Polyketides produced by modular type I polyketide synthases (PKSs) play eminent roles in the development of medicines. Yet, the production of structural analogs by genetic engineering poses a major challenge. We report an evolution-guided morphing of modular PKSs inspired by recombination processes that lead to structural diversity in nature. By deletion and insertion of PKS modules we interconvert the assembly lines for related antibiotic and antifungal agents, aureothin (aur) and neoaureothin (nor) (aka spectinabilin), in both directions. Mutational and functional analyses of the polyketide-tailoring cytochrome P450 monooxygenases, and PKS phylogenies give contradictory clues on potential evolutionary scenarios (generalist-to-specialist enzyme evolution vs. most parsimonious ancestor). The KS-AT linker proves to be well suited as fusion site for both excision and insertion of modules, which supports a model for alternative module boundaries in some PKS systems. This study teaches important lessons on the evolution of PKSs, which may guide future engineering approaches.


Assuntos
Cromonas/metabolismo , Oxigenases/metabolismo , Policetídeo Sintases/metabolismo , Policetídeos/metabolismo , Streptomyces/metabolismo , Sequência de Aminoácidos , Antibacterianos/química , Antibacterianos/metabolismo , Cromonas/química , Engenharia Genética/métodos , Modelos Químicos , Estrutura Molecular , Mutação , Filogenia , Policetídeo Sintases/classificação , Policetídeo Sintases/genética , Policetídeos/química , Streptomyces/genética
7.
J Microbiol Biotechnol ; 29(10): 1570-1579, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31474098

RESUMO

The fungal products dibenzodioxocinones promise a novel class of inhibitors against cholesterol ester transfer protein (CEPT). Knowledge as to their biosynthesis is scarce. In this report, we characterized four more dibenzodioxocinones, which along with a previously described member pestalotiollide B, delimit the dominant spectrum of secondary metabolites in P. microspora. Through mRNA-seq profiling in gα1Δ, a process that halts the production of the dibenzodioxocinones, a gene cluster harboring 21 genes including a polyketide synthase, designated as pks8, was defined. Disruption of genes in the cluster led to loss of the compounds, concluding the anticipated role in the biosynthesis of the chemicals. The biosynthetic route to dibenzodioxocinones was temporarily speculated. This study reveals the genetic basis underlying the biosynthesis of dibenzodioxocinone in fungi, and may facilitate the practice for yield improvement in the drug development arena.


Assuntos
Família Multigênica , Policetídeos/metabolismo , Xylariales/genética , Vias Biossintéticas , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Endófitos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Perfilação da Expressão Gênica , Família Multigênica/genética , Mutação , Paclitaxel/biossíntese , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Policetídeos/química , Xylariales/química , Xylariales/metabolismo
8.
Science ; 365(6457)2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31395743

RESUMO

Colibactin is a complex secondary metabolite produced by some genotoxic gut Escherichia coli strains. The presence of colibactin-producing bacteria correlates with the frequency and severity of colorectal cancer in humans. However, because colibactin has not been isolated or structurally characterized, studying the physiological effects of colibactin-producing bacteria in the human gut has been difficult. We used a combination of genetics, isotope labeling, tandem mass spectrometry, and chemical synthesis to deduce the structure of colibactin. Our structural assignment accounts for all known biosynthetic and cell biology data and suggests roles for the final unaccounted enzymes in the colibactin gene cluster.


Assuntos
Adutos de DNA/química , Peptídeos/química , Policetídeos/química , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Marcação por Isótopo , Mutação , Peptídeo Hidrolases/genética , Peptídeos/genética , Peptídeos/metabolismo , Policetídeos/metabolismo , Conformação Proteica , Metabolismo Secundário , Espectrometria de Massas em Tandem
9.
Chem Biodivers ; 16(9): e1900326, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31368179

RESUMO

Chromatographic separation of the AcOEt extract of the fermented cultures of the deep-sea-derived fungus Graphostroma sp. resulted in the isolation of 11 new chained polyketides, namely graphostromols A-K (1-11). The structures of the new compounds were established by the extensive analyses of their NMR and HR-ESI-MS data. The absolute configuration at C-11 in 1 was determined on the basis of the modified Mosher's method. Compounds 1-5, bearing a 2,2,10,10-tetramethyldodecane skeleton, were discovered for the first time from nature. All isolates were evaluated for their cytotoxicities against five different cancer cell lines (HeLa, Eca-109, Biu-87, Bel-7402, and PANC-1). However, none showed positive effects.


Assuntos
Policetídeos/química , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Policetídeos/isolamento & purificação
10.
J Appl Microbiol ; 127(6): 1727-1740, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31454455

RESUMO

AIMS: To identify and assess the biological activities of the crude extract of a Streptomyces isolate from a salty wetland, an extreme environment likely to induce secondary metabolism of micro-organisms. METHODS AND RESULTS: The crude extract from the isolate Streptomyces lanatus strain AR2 displayed antibacterial activity against Gram-positive bacteria (MICs ranging from 5 to 50 µg ml-1 ) and antioxidant activity as revealed in DPPH (2,2-diphenyl-1-picrylhydrazyl) assay (IC50 of 0·74 mg ml-1 ), ferric reducing antioxidant power (IC50 of 1·12 mg ml-1 ) and metal-chelating power (IC50 of 1·84 mg ml-1 ) assays. Accordingly, the extract attenuated the H2 O2 -induced oxidative stress in the eukaryotic cell model Saccharomyces cerevisiae, assessed by flow cytometry. The profiling of secondary metabolites by HPLC-PDA-ESI-MS/MS revealed the presence of 17 compounds, some of which reported in Streptomyces for the first time to the best of our knowledge: genistein-7-O-glucuronide, naringenin-7-O-rutinoside and resveratrol. CONCLUSIONS: Streptomyces lanatus AR2 produced unique polyketides and phenolic compounds with noticeable bioactivities, allowing adaptation to the extreme environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Sabkhat Seijoumi salty wetland represents a potential niche for Streptomyces yielding useful natural products for biotechnological, pharmaceutical and medical applications.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Streptomyces/química , Antibacterianos/química , Antioxidantes/química , Testes de Sensibilidade Microbiana , Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Policetídeos/química , Metabolismo Secundário , Streptomyces/isolamento & purificação , Streptomyces/metabolismo , Áreas Alagadas
11.
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
12.
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
13.
PLoS Biol ; 17(7): e3000347, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31318855

RESUMO

Polyketides are a class of specialised metabolites synthesised by both eukaryotes and prokaryotes. These chemically and structurally diverse molecules are heavily used in the clinic and include frontline antimicrobial and anticancer drugs such as erythromycin and doxorubicin. To replenish the clinicians' diminishing arsenal of bioactive molecules, a promising strategy aims at transferring polyketide biosynthetic pathways from their native producers into the biotechnologically desirable host Escherichia coli. This approach has been successful for type I modular polyketide synthases (PKSs); however, despite more than 3 decades of research, the large and important group of type II PKSs has until now been elusive in E. coli. Here, we report on a versatile polyketide biosynthesis pipeline, based on identification of E. coli-compatible type II PKSs. We successfully express 5 ketosynthase (KS) and chain length factor (CLF) pairs-e.g., from Photorhabdus luminescens TT01, Streptomyces resistomycificus, Streptoccocus sp. GMD2S, Pseudoalteromonas luteoviolacea, and Ktedonobacter racemifer-as soluble heterodimeric recombinant proteins in E. coli for the first time. We define the anthraquinone minimal PKS components and utilise this biosynthetic system to synthesise anthraquinones, dianthrones, and benzoisochromanequinones (BIQs). Furthermore, we demonstrate the tolerance and promiscuity of the anthraquinone heterologous biosynthetic pathway in E. coli to act as genetically applicable plug-and-play scaffold, showing it to function successfully when combined with enzymes from phylogenetically distant species, endophytic fungi and plants, which resulted in 2 new-to-nature compounds, neomedicamycin and neochaetomycin. This work enables plug-and-play combinatorial biosynthesis of aromatic polyketides using bacterial type II PKSs in E. coli, providing full access to its many advantages in terms of easy and fast genetic manipulation, accessibility for high-throughput robotics, and convenient biotechnological scale-up. Using the synthetic and systems biology toolbox, this plug-and-play biosynthetic platform can serve as an engine for the production of new and diversified bioactive polyketides in an automated, rapid, and versatile fashion.


Assuntos
Antraquinonas/metabolismo , Proteínas de Bactérias/metabolismo , Escherichia coli/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Policetídeo Sintases/metabolismo , Policetídeos/metabolismo , Proteínas Recombinantes/metabolismo , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/classificação , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/genética , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Antraquinonas/química , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Vias Biossintéticas , Escherichia coli/genética , Modelos Químicos , Estrutura Molecular , Filogenia , Hidrocarbonetos Policíclicos Aromáticos/química , Policetídeo Sintases/química , Policetídeo Sintases/genética , Policetídeos/química , Proteínas Recombinantes/química
14.
Nat Chem Biol ; 15(8): 795-802, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31308531

RESUMO

Glycosylation is a common modification reaction in natural product biosynthesis and has been known to be a post-assembly line tailoring process in glycosylated polyketide biosynthesis. Here, we show that in pactamycin biosynthesis, glycosylation can take place on an acyl carrier protein (ACP)-bound polyketide intermediate. Using in vivo gene inactivation, chemical complementation and in vitro pathway reconstitution, we demonstrate that the 3-aminoacetophenone moiety of pactamycin is derived from 3-aminobenzoic acid by a set of discrete polyketide synthase proteins via a 3-(3-aminophenyl)3-oxopropionyl-ACP intermediate. This ACP-bound intermediate is then glycosylated by an N-glycosyltransferase, PtmJ, providing a sugar precursor for the formation of the aminocyclopentitol core structure of pactamycin. This is the first example of glycosylation of a small molecule while tethered to a carrier protein. Additionally, we demonstrate that PtmO is a hydrolase that is responsible for the release of the ACP-bound product to a free ß-ketoacid that subsequently undergoes decarboxylation.


Assuntos
Proteínas de Transporte/metabolismo , Pactamicina/biossíntese , Streptomyces/metabolismo , Proteínas de Bactérias , Proteínas de Transporte/química , Clonagem Molecular , Regulação Bacteriana da Expressão Gênica , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Policetídeos/química , Ligação Proteica
15.
Nat Chem Biol ; 15(8): 813-821, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31308532

RESUMO

Bacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) are among the most complex known enzymes from secondary metabolism and are responsible for the biosynthesis of highly diverse bioactive polyketides. However, most of these metabolites remain uncharacterized, since trans-AT PKSs frequently occur in poorly studied microbes and feature a remarkable array of non-canonical biosynthetic components with poorly understood functions. As a consequence, genome-guided natural product identification has been challenging. To enable de novo structural predictions for trans-AT PKS-derived polyketides, we developed the trans-AT PKS polyketide predictor (TransATor). TransATor is a versatile bio- and chemoinformatics web application that suggests informative chemical structures for even highly aberrant trans-AT PKS biosynthetic gene clusters, thus permitting hypothesis-based, targeted biotechnological discovery and biosynthetic studies. We demonstrate the applicative scope in several examples, including the characterization of new variants of bioactive natural products as well as structurally new polyketides from unusual bacterial sources.


Assuntos
Bactérias/enzimologia , Policetídeo Sintases/metabolismo , Policetídeos/metabolismo , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Produtos Biológicos , Modelos Químicos , Filogenia , Policetídeo Sintases/genética , Policetídeos/química , Poríferos/microbiologia , Domínios Proteicos , Especificidade por Substrato
16.
Mar Drugs ; 17(8)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344982

RESUMO

Advances in whole-genome sequencing of many fungal species has revealed the presence of numerous "silent" biosynthetic genes, highlighting their potential to produce a wide variety of natural products. These silent biosynthetic genes are regulated in part by their highly condensed chromatin structure, which can be modified to allow transcription in response to external stimuli. In this study, Asteromyces cruciatus was subjected to both epigenetic modification and osmotic stress to enhance the production of new natural products. This "cooperative induction" strategy led to the isolation and characterization of two new polyketides from a fermentation of A. cruciatus treated with suberoylanilide hydroxamic acid and sodium chloride. The metabolic profiles of the control and treated samples were assessed using ultra-high performance liquid chromatography high-resolution electrospray ionization mass spectrometry (UHPLC-HRESIMS) metabolomic analysis, highlighting the upregulation of two new polyketides, primarolides A and B. These compounds were purified using reversed-phase flash chromatography followed by high-performance liquid chromatography, and their planar structures were established using NMR spectroscopy.


Assuntos
Organismos Aquáticos/química , Ascomicetos/química , Ascomicetos/efeitos dos fármacos , Produtos Biológicos/química , Ácidos Hidroxâmicos/farmacologia , Osmose/fisiologia , Policetídeos/química , Ascomicetos/fisiologia , Cromatografia Líquida de Alta Pressão/métodos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Cloreto de Sódio/farmacologia
17.
Zhongguo Zhong Yao Za Zhi ; 44(10): 2090-2095, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31355566

RESUMO

To isolate and identify secondary metabolites of marine-derived Streptomyces sp.MDW-06,the isolations and purifications of compounds were performed by means of column chromatography over silica gel. And their structures were elucidated through the spectroscopic analysis of MS,NMR and specific rotations. The bioactivities were assayed by paper diffusion and DPPH method. From the fermentation broth of marine-derived Streptomyces sp.MDW-06,five compounds( 1-5) were isolated and identified as streptopentanoic acid( 1),germicidin A( 2),germicidin B( 3),isogermicidin A( 4),isogermicidin B( 5) and oxohygrolidin( 6),respectively. Compound 1 is a new compound. Compound 1 shows DPPH radical scavenging activity with 36. 4% at 100 mg·L~(-1).


Assuntos
Depuradores de Radicais Livres/química , Policetídeos/química , Streptomyces/química , Cromatografia , Fermentação , Depuradores de Radicais Livres/isolamento & purificação , Espectroscopia de Ressonância Magnética , Policetídeos/isolamento & purificação
18.
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
19.
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
20.
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
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