Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Nat Prod ; 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35427139

RESUMO

Investigation of the marine sponge Agelas dispar MeOH fractions using feature-based molecular networking, dereplication, and isolation led to the discovery of new bromopyrrole-derived metabolites. An in-house library of bromopyrrole alkaloids previously isolated from A. dispar and Dictyonella sp. was utilized, along with the investigation of an MS/MS fragmentation of these compounds. Our strategy led to the isolation and identification of the disparamides A-C (1-3), with a novel carbon skeleton. Additionally, new dispyrins B-F (4-8) and nagelamides H2 and H3 (9 and 10) and known nagelamide H (11), citrinamine B (12), ageliferin (13), bromoageliferin (14), and dibromoageliferin (15) were also isolated and identified by analysis of spectroscopic data. Analysis of MS/MS fragmentation data and molecular networking analysis indicated the presence of hymenidin (16), oroidin (17), dispacamide (18), monobromodispacamide (19), keramadine (20), longamide B (21), methyl ester of longamide B (22), hanishin (23), methyl ester of 3-debromolongamide B (24), and 3-debromohanishin (25). Antibacterial activity of ageliferin (13), bromoageliferin (14), and dibromoageliferin (15) was evaluated against susceptible and multi-drug-resistant ESKAPE pathogenic bacteria Klabsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterococcus faecalis. Dibromoageliferin (15) displayed the most potent antimicrobial activity against all tested susceptible and MDR strains. Compounds 13-15 presented no significant hemolytic activity up to 100 µM.

2.
Arch Pharm (Weinheim) ; 355(4): e2100441, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35099085

RESUMO

Microbial strains isolated from extreme and understudied environments, such as caves, are still poorly investigated for the production of bioactive secondary metabolites. Investigation of the ethyl acetate extract from the growth medium produced by the soil-derived fungus Aspergillus sp. SDC28, isolated from a Brazilian cave, yielded two anthraquinones: versicolorin C (1) and versiconol (2). The complete assignment of nuclear magnetic resonance and mass spectroscopic data of 1 and 2 was performed for the first time. Moreover, the yet unreported absolute configuration of both compounds was unambiguously established by analysis of experimental and theoretical electronic circular dichroism data. Vibrational circular dichroism was also applied to confirm the absolute stereochemistry of 2. Compounds 1 and 2 showed cytotoxic activity against human ovarian cancer cells (OVCAR3).


Assuntos
Cavernas , Neoplasias Ovarianas , Antraquinonas/farmacologia , Apoptose , Aspergillus/química , Aspergillus/metabolismo , Brasil , Linhagem Celular Tumoral , Dicroísmo Circular , Feminino , Humanos , Estrutura Molecular , Oligodesoxirribonucleotídeos , Solo , Relação Estrutura-Atividade , Tionucleotídeos
3.
Nat Prod Rep ; 39(3): 596-669, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-34647117

RESUMO

Covering period: up to 2019Water-soluble natural products constitute a relevant group of secondary metabolites notably known for presenting potent biological activities. Examples are aminoglycosides, ß-lactam antibiotics, saponins of both terrestrial and marine origin, and marine toxins. Although extensively investigated in the past, particularly during the golden age of antibiotics, hydrophilic fractions have been less scrutinized during the last few decades. This review addresses the possible reasons on why water-soluble metabolites are now under investigated and describes approaches and strategies for the isolation of these natural compounds. It presents examples of several classes of hydrosoluble natural products and how they have been isolated. Novel stationary phases and chromatography techniques are also reviewed, providing a perspective towards a renaissance in the investigation of water-soluble natural products.


Assuntos
Produtos Biológicos , Antibacterianos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Cromatografia , Toxinas Marinhas , Água
4.
J Nat Prod ; 83(6): 1784-1793, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32525315

RESUMO

Herein reported are results of the chemical and biological investigation of red propolis collected at the Brazilian Northeast coastline. New propolones A-D (1-4), with a 3-{3-[(2-phenylbenzofuran-3-yl)methyl]phenyl}chromane skeleton; propolonones A-C (5-7), with a 3-[3-(3-benzylbenzofuran-2-yl)phenyl]chromane skeleton; and propolol A (8), with a 6-(3-benzylbenzofuran-2-yl)-3-phenylchromane skeleton, were isolated as constituents of Brazilian red propolis by cytotoxicity-guided assays and structurally identified by analysis of their spectroscopic data. Propolone B (2) and propolonone A (5) display significant cytotoxic activities against an ovarian cancer cell line expressing a multiple drug resistance phenotype when compared with doxorubicin.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Própole/química , Antibióticos Antineoplásicos/farmacologia , Brasil , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Neoplasias Ovarianas/tratamento farmacológico
5.
J Nat Prod ; 83(1): 55-65, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31895573

RESUMO

A new method of screening was developed to generate 770 organic and water-soluble fractions from extracts of nine species of marine sponges, from the growth media of 18 species of marine-derived fungi, and from the growth media of 13 species of endophytic fungi. The screening results indicated that water-soluble fractions displayed significant bioactivity in cytotoxic, antibiotic, anti-Leishmania, anti-Trypanosoma cruzi, and inhibition of proteasome assays. Purification of water-soluble fractions from the growth medium of Penicillium solitum IS1-A provided the new glutamic acid derivatives solitumine A (1), solitumine B (2), and solitumidines A-D (3-6). The structures of compounds 1-6 have been established by analysis of spectroscopic data, chemical derivatizations, and vibrational circular dichroism calculations. Although no biological activity could be observed for compounds 1-6, the new structures reported for 1-6 indicate that the investigation of water-soluble natural products represents a relevant strategy in finding new secondary metabolites.


Assuntos
Glutamatos/química , Regiões Antárticas , Fungos/química , Estrutura Molecular , Penicillium/química , Água
6.
Chemosphere ; 242: 125211, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31896201

RESUMO

While tetrodotoxin (TTX) is commonly found in pufferfish tissues, it is unclear if bacterial symbionts isolated from pufferfish tissues can produce TTX. In this investigation, UPLC qTOF-MS/MS analysis of tissue extracts obtained from Sphoeroides spengleri and Canthigaster figuereidoi identified TTX in their composition, indicating their consumption is unsafe. UPLC qTOF-MS/MS analysis coupled with Molecular Networking indicated new TTX analogs (methyl-TTX, TTX-acetate, hydroxypropyl-TTX and glycerol-TTX). Bacterial extracts from sixteen strains revealed a compound with a [M+H]+ ion at m/z 320.1088, identical to TTX. However, TTX itself was not detected in these cultures by UPLC-MS/MS. Neurotoxicity of Vibrio A665 purified fraction 2 (with precursor [M+H]+ ion at m/z 320.1088) was significant in human neural stem cells (hNSCs), but the Nav blockage activity was not confirmed by the veratridine/ouabain essays, indicating a possible difference in the mechanism of action between the bacterium A665 purified fraction 2 and TTX. Vibrios symbionts of pufferfish point out involving in the production of TTX precursors.


Assuntos
Microbiota , Tetraodontiformes/fisiologia , Tetrodotoxina/metabolismo , Animais , Brasil , Cromatografia Líquida , Humanos , Espectrometria de Massas em Tandem , Tetraodontiformes/microbiologia , Vibrio
7.
Nat Prod Rep ; 36(7): 981-1004, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31049509

RESUMO

Covering: up to 2019The discovery of new bioactive natural products gained momentum during the last few decades, resulting from instrumentation advances, from the expansion of genome mining and regulation, as well as by exploration of untapped biological sources. However, water-soluble, volatile, minor and photosensitive natural products are yet poorly known. This review discusses the literature reporting the isolation strategies for some of these metabolites. Analysis of minor metabolites at sub-milligram level are also presented, since analytical instrumentation enabling structure assignment in minute quantities is now routine. Major trends related to natural products discovery are discussed, under the light of further developments in biodiscovery.


Assuntos
Produtos Biológicos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/efeitos da radiação , Interações Hidrofóbicas e Hidrofílicas , Luz , Estrutura Molecular , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/isolamento & purificação , Compostos Orgânicos Voláteis/efeitos da radiação
8.
J Nat Prod ; 81(10): 2296-2300, 2018 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-30281303

RESUMO

The new pyrrole-imidazole and pyrrole-guanidine alkaloids 4-debromooroidin (1), 4-debromougibohlin (2), 5-debromougibohlin (3), and 5-bromopalau'amine (4), along with the known hymenidin (5) and (+)-monobromoisophakellin (6), have been isolated from a Dictyonella sp. marine sponge, collected at the Amazon River mouth. The bromine-substitution pattern observed for compounds 1, 2 and 4 is unusual among bromopyrrole alkaloids isolated from marine sponges. The 20S proteasome inhibitory activities of compounds 1-6 have been recorded, with 5-bromopalau'amine (4) being the most active in this series.


Assuntos
Poríferos/química , Inibidores de Proteassoma/química , Inibidores de Proteassoma/farmacologia , Pirróis/química , Pirróis/farmacologia , Animais , Brasil , Estrutura Molecular , Complexo de Endopeptidases do Proteassoma , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética
9.
Nat Chem ; 10(9): 938-945, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30061613

RESUMO

Studies of secondary metabolites (natural products) that cover their isolation, chemical synthesis and bioactivity investigation present myriad opportunities for discovery. For example, the isolation of novel secondary metabolites can inspire advances in chemical synthesis strategies to achieve their practical preparation for biological evaluation. In the process, chemical synthesis can also provide unambiguous structural characterization of the natural products. Although the isolation, chemical synthesis and bioactivity studies of natural products are mutually beneficial, they are often conducted independently. Here, we demonstrate the benefits of a collaborative study of the phomactins, diterpenoid fungal metabolites that serve as antagonists of the platelet activating factor receptor. Our isolation of novel phomactins has spurred the development of a bioinspired, unified approach that achieves the total syntheses of six congeners. We also demonstrate in vitro the beneficial effects of several phomactins in suppressing the rate of repopulation of tumour cells following gamma radiation therapy.


Assuntos
Produtos Biológicos/síntese química , Terpenos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Fungos/química , Fungos/metabolismo , Raios gama , Humanos , Concentração Inibidora 50 , Glicoproteínas da Membrana de Plaquetas/antagonistas & inibidores , Glicoproteínas da Membrana de Plaquetas/metabolismo , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Terpenos/isolamento & purificação , Terpenos/farmacologia
10.
Bioorg Med Chem ; 25(6): 1860-1866, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28202316

RESUMO

Incorporation of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), to a culture broth of the endophytic fungus Phoma sp. nov. LG0217 isolated from Parkinsonia microphylla changed its metabolite profile and resulted in the production of (10'S)-verruculide B (1), vermistatin (2) and dihydrovermistatin (3). When cultured in the absence of the epigenetic modifier, it produced a new metabolite, (S,Z)-5-(3',4'-dihydroxybutyldiene)-3-propylfuran-2(5H)-one (4) together with nafuredin (5). The structure of 4 was elucidated by spectroscopic analyses and its absolute configuration was determined by application of the modified Mosher's ester method. The absolute structure of (10'S)-verruculide B was determined as 5-[(10'S,2'E,6'E)-10',11'-dihydroxy-3',7',11'-trimethyldodeca-2',6'-dien-1'-yl]-(3R)-6,8-dihydroxy-3-methylisochroman-1-one (1) with the help of CD and NOE data. Compound 1 inhibited the activity of protein tyrosine phosphatases (PTPs) 1B (PTP1B), Src homology 2-containing PTP 1 (SHP1) and T-cell PTP (TCPTP) with IC50 values of 13.7±3.4, 8.8±0.6, and 16.6±3.8µM, respectively. Significance of these activities and observed modest selectivity of 1 for SHP1 over PTP1B and TCPTP is discussed.


Assuntos
Ascomicetos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Epigênese Genética/efeitos dos fármacos , Fabaceae/microbiologia , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Sesquiterpenos/metabolismo , Ascomicetos/metabolismo , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/química , Espectroscopia de Ressonância Magnética , Sesquiterpenos/química , Sesquiterpenos/farmacologia
11.
J Nat Prod ; 80(3): 720-725, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28191951

RESUMO

Marine sponges are a rich source of terpenoids with rearranged spongian carbon skeletons. Investigation of extracts from the sponge Darwinella cf. oxeata yielded four new rearranged diterpenoids, oxeatine (2) and oxeatamides H-J (3-5), as well as the known metabolites oxeatamide A (6), oxeatamide A methyl ester (7), and membranolide (1). Oxeatine (2) has a new heterocyclic skeleton, while oxeatamide J (5) has an N-methyl urea group included in a γ-lactam moiety. UPLC-QTOF analysis of the extract obtained from the mantle of the nudibranch Felimida grahami indicated the presence of 1 and 4.


Assuntos
Diterpenos/química , Diterpenos/isolamento & purificação , Gastrópodes/química , Poríferos/química , Terpenos/química , Terpenos/isolamento & purificação , Animais , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
12.
J Nat Prod ; 77(3): 668-72, 2014 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-24588269

RESUMO

Two new eremophilane-type sesquiterpenes, xylarenones F (3) and G (4), have been isolated from solid substrate cultures of a Camarops sp. endophytic fungus isolated from Alibertia macrophylla, together with the known compounds xylarenones C (1) and D (2). The structures and relative configurations of 1-4 were elucidated by extensive NMR and HRESIMS spectroscopic analysis. Due to their effects on the respiratory burst of neutrophils, which included inhibition of the reactive oxygen species production, these sesquiterpenes exhibited potential anti-inflammatory and antioxidant properties.


Assuntos
Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Ascomicetos/química , Rubiaceae/microbiologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Anti-Inflamatórios não Esteroides/química , Antioxidantes/química , Brasil , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Espécies Reativas de Oxigênio/antagonistas & inibidores , Sesquiterpenos/química , Azul Tripano
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...