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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.
Fitoterapia ; 137: 104249, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31247219

RESUMO

Two azaphilone pigments (1 and 2), two dihydrobenzofurans (3 and 4), two macrodiolides (5 and 6), and a dimeric alkyl aromatic constituent (7) were isolated from the goose dung-derived fungus Coniella fragariae. Compounds 1-3 proved to be new natural products. Coniellins H and I (1 and 2) feature a tetracyclic core and an aldehyde group at C-5, which is unusual for azaphilone derivatives. The X-ray structure of pyrenophorin (5) is reported for the first time. Pyrenophorin (5) showed strong cytotoxicity against several cancer cell lines with IC50 values ranging from 0.07 to 7.8 µM.


Assuntos
Ascomicetos/química , Benzopiranos/farmacologia , Pigmentos Biológicos/farmacologia , Animais , Benzofuranos/isolamento & purificação , Benzopiranos/isolamento & purificação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Fezes/microbiologia , Gansos/microbiologia , Alemanha , Humanos , Estrutura Molecular , Mar do Norte , Pigmentos Biológicos/isolamento & purificação
3.
J Nat Prod ; 81(11): 2493-2500, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30354103

RESUMO

Seven new azaphilones, coniellins A-G (1-7), were obtained from the fungus Coniella fragariae that had been isolated from goose dung. Their structures were elucidated by analysis of 1D and 2D NMR as well as HRESIMS data. TDDFT-ECD calculation was used to determine the absolute configuration of 1, while Mosher's method was applied to determine the absolute configuration of 5. While displaying only moderate cytotoxicity, compound 1 exhibited significant inhibition of NF-κB activation in the triple negative breast cancer cell line MDA-MB-231 with an IC50 value of 4.4 µM. Moreover, compounds 1, 4, and 5 clearly reduced tumor cell migration. Compound 1 was the most active derivative tested in this assay and displayed 60% inhibition of tumor cell migration at a dose of 5 µM and 98% inhibition at 10 µM after 24 h.


Assuntos
Antineoplásicos/isolamento & purificação , Ascomicetos/química , Benzopiranos/química , NF-kappa B/antagonistas & inibidores , Pigmentos Biológicos/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzopiranos/isolamento & purificação , Benzopiranos/farmacologia , Linhagem Celular Tumoral , Inibição de Migração Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Pigmentos Biológicos/isolamento & purificação , Pigmentos Biológicos/farmacologia
4.
Dev Cell ; 20(3): 342-52, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21397845

RESUMO

Proper bipolar attachment of sister kinetochores to the mitotic spindle is critical for accurate chromosome segregation in mitosis. Here we show an essential role of the formin mDia3 in achieving metaphase chromosome alignment. This function is independent of mDia3 actin nucleation activity, but is attributable to EB1-binding by mDia3. Furthermore, the microtubule binding FH2 domain of mDia3 is phosphorylated by Aurora B kinase in vitro, and cells expressing the nonphosphorylatable mDia3 mutant cannot position chromosomes at the metaphase plate. Purified recombinant mDia3 phosphorylated by Aurora B exhibits reduced ability to bind microtubules and stabilize microtubules against cold-induced disassembly in vitro. Cells expressing the phosphomimetic mDia3 mutant do not form stable kinetochore microtubule fibers; despite they are able to congress chromosomes to the metaphase plate. These findings reveal a key role for mDia3 and its regulation by Aurora B phosphorylation in achieving proper stable kinetochore microtubule attachment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Cromossomos/metabolismo , Metáfase/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Aurora Quinase B , Aurora Quinases , Segregação de Cromossomos , Cromossomos/ultraestrutura , Células HeLa , Humanos , Cinetocoros/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Fosforilação , Fuso Acromático/metabolismo
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