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Cytotoxic, immunosuppressive and trypanocidal activities of agrocybin, a polyacetylene produced by Agrocybe perfecta (Basidiomycota)

机译:农杆菌肽的细胞毒性,免疫抑制和锥虫活性,农杆菌肽是一种由完美农杆菌(Basidiomycota)生产的聚乙炔

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摘要

The ethyl acetate extract from the culture of the fungus Agrocybe perfecta (Rick) Singer was selected for further study in a screening of Brazilian basidiomycetes for bioactivity. The extract showed significant activity against the recombinant enzyme trypanothione reductase (TryR) from Trypanosoma cruzi, lymphocyte proliferation in human peripheral mononuclear cells (PBMC) stimulated with phytohemaglutinin (PHA), and the human cancer cell lines UACC-62 (melanoma), MCF-7 (mammary), and TK-10 (kidney). The chromatographic fractionation of the extract was monitored by the above bioassays and showed that agrocybin was the active component. Agrocybin, a known polyacetylene amide, showed an IC50 of 2 μM in the TryR assay but killed only 60% of the trypomastigote form of T. cruzi in infected murine blood even at 680 μM. This weaker activity could be due to the low temperature used to mimic banked blood or as a consequence of its inactivation by blood, already reported in the literature. On the other hand, it inhibited the proliferation of PBMC by 50% at 3.4 μM and the growth of the cancer cell lines at concentrations between 9 and 24.5 μM. Measurements of DNA fragmentation using flow cytometry suggest that agrocybin promotes cell death via apoptosis.
机译:选择来自农杆菌(Rick)Singer真菌培养物中的乙酸乙酯提取物,以进一步筛选巴西担子菌的生物活性。提取物显示出抗克氏锥虫重组酶锥虫硫醇还原酶(TryR)的显着活性,植物血凝素(PHA)刺激的人外周血单个核细胞(PBMC)中的淋巴细胞增殖以及人癌细胞系UACC-62(黑素瘤),MCF- 7(乳腺)和TK-10(肾脏)。通过上述生物测定法监测提取物的色谱分离,结果表明农杆菌肽是活性成分。农杆菌肽,一种已知的聚乙炔酰胺,在TryR分析中显示出2μM的IC50,但即使在680μM的情况下,也只能杀死60%的被感染鼠科动物的锥虫伪装形式。这种较弱的活性可能是由于用于模拟堆积的血液的低温或由于其已被血液灭活所致,已在文献中进行了报道。另一方面,它在3.4μM下抑制PBMC增殖50%,在9至24.5μM之间抑制癌细胞系的生长。使用流式细胞仪对DNA片段的测量表明,农杆菌肽可通过凋亡促进细胞死亡。

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    Laboratório de Química de Produtos Naturais Av. Augusto de Lima 1715 CEP 30190-002 Belo Horizonte MG Brasil;

    Laboratório de Química de Produtos Naturais Av. Augusto de Lima 1715 CEP 30190-002 Belo Horizonte MG Brasil;

    Fundação Centro Tecnológico de Minas Gerais CETEC av. José Cândido da Silveira 2000 Belo Horizonte Brasil;

    Laboratório de Química de Produtos Naturais Av. Augusto de Lima 1715 CEP 30190-002 Belo Horizonte MG Brasil;

    Laboratório de Doenças de Chagas Av. Augusto de Lima 1715 CEP 30190-002 Belo Horizonte MG Brasil;

    Laboratório de Parasitologia Celular e Molecular Av. Augusto de Lima 1715 CEP 30190-002 Belo Horizonte MG Brasil;

    Laboratório de Imunologia Celular e Molecular Av. Augusto de Lima 1715 CEP 30190-002 Belo Horizonte MG Brasil;

    Departamento de Microbiologia Instituto de Ciências Biológicas Universidade Federal de Minas Gerais Caixa Postal 486 CEP 30123-970 Belo Horizonte MG Brasil;

    Laboratório de Química de Produtos Naturais Av. Augusto de Lima 1715 CEP 30190-002 Belo Horizonte MG Brasil;

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  • 正文语种 eng
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  • 关键词

    Basidiomycetes; cancer cells; lymphocytes; PBMC; trypanothione reductase; Trypanosoma cruzi;

    机译:担子菌;癌细胞;淋巴细胞PBMC;锥虫硫醇还原酶;克氏锥虫;

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