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抗阴道毛滴虫活性和海洋来源真菌代谢产物的化学分析。

Anti-Trichomonas vaginalis activity and chemical analysis of metabolites produced by marine-associated fungi.

机构信息

Faculdade de Farmácia, Universidade Federal Do Rio Grande Do Sul, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil.

Centro de Biotecnologia Do Estado de Rio Grande Do Sul, Universidade Federal Do Rio Grande Do Sul, Porto AlegrePorto Alegre, RS, Brazil.

出版信息

Parasitol Res. 2022 Mar;121(3):981-989. doi: 10.1007/s00436-022-07442-6. Epub 2022 Feb 3.

DOI:10.1007/s00436-022-07442-6
PMID:35113221
Abstract

Trichomoniasis is the most common non-viral sexually transmitted infection worldwide and it may have serious consequences, especially for women. Currently, 5-nitroimidazole drugs are the treatment of choice for trichomoniasis, although presenting adverse effects and reported cases of drug resistance. Metabolites isolated from marine fungi have attracted considerable attention due to their unique chemical structures with diverse biological activities, including antiprotozoal activity. In this study, we showed the anti-Trichomonas vaginalis activity of fractions obtained from marine fungi and the chemical composition of the most active fraction was determined. Ethyl acetate fractions of the fungus Aspergillus niger (EAE03) and Trichoderma harzianum/Hypocrea lixii complex (EAE09) were active against T. vaginalis. These samples, EAE03 and EAE09, were also effective against the fresh clinical isolate metronidazole-resistant TV-LACM2R, presenting MIC values of 2.0 mg/mL and 1.0 mg/mL, respectively. The same MIC values were found against ATCC 30,236 T. vaginalis isolate. In vitro cytotoxicity revealed only the fraction named EAE03 with no cytotoxic effect; however, the active fractions did not promote a significant hemolytic effect after 1-h incubation. Already, the in vivo toxicity evaluation using Galleria mellonella larvae demonstrated that none of the tested samples caused a reduction in animal survival. The fraction EAE03 was followed for purification steps and analyzed by LC-DAD-MS. Eleven compounds were annotated, including butyrolactone, butanolide, and atromentin. Overall, the range of activities reported confirms the potential of marine fungi to produce bioactive molecules.

摘要

滴虫病是全球最常见的非病毒性性传播感染疾病,可能会产生严重后果,尤其是对女性而言。目前,5-硝基咪唑类药物是治疗滴虫病的首选药物,但也存在不良反应和耐药病例的报道。从海洋真菌中分离得到的代谢产物因其独特的化学结构和多样化的生物活性而备受关注,包括抗原生动物活性。在这项研究中,我们展示了海洋真菌提取物的抗阴道毛滴虫活性,并确定了最具活性的部分的化学成分。真菌黑曲霉(EAE03)和哈茨木霉/ Hypocrea lixii 复合体(EAE09)的乙酸乙酯部分对阴道毛滴虫具有活性。这些样品,EAE03 和 EAE09,对新鲜临床分离的甲硝唑耐药 TV-LACM2R 也有效,MIC 值分别为 2.0 和 1.0mg/mL。对 ATCC 30,236 阴道毛滴虫分离株也发现了相同的 MIC 值。体外细胞毒性仅显示出无细胞毒性作用的 EAE03 部分;然而,活性部分在 1 小时孵育后并没有促进明显的溶血作用。已经使用家蚕幼虫进行了体内毒性评估,证明没有一种测试样本会降低动物的存活率。EAE03 部分进行了进一步的纯化步骤,并通过 LC-DAD-MS 进行了分析。注释了 11 种化合物,包括丁内酯、丁烯内酯和阿特莫宁。总体而言,所报道的活性范围证实了海洋真菌产生生物活性分子的潜力。

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本文引用的文献

1
Identification of Gliotoxin isolated from marine fungus as a new pyruvate kinase M2 inhibitor.鉴定海洋真菌来源的Gliotoxin 为一种新的丙酮酸激酶 M2 抑制剂。
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Management of Resistant Trichomoniasis.耐药性滴虫病的管理
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Have marine natural product drug discovery efforts been productive and how can we improve their efficiency?海洋天然产物药物研发工作是否富有成效,我们又如何提高其效率?
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Anti-Trichomonas vaginalis activity of chalcone and amino-analogues.查耳酮及其氨基类似物的抗阴道毛滴虫活性。
Parasitol Res. 2019 Feb;118(2):607-615. doi: 10.1007/s00436-018-6164-4. Epub 2018 Dec 7.
9
Galleria mellonella larvae allow the discrimination of toxic and non-toxic chemicals.家蚕幼虫可用于区分有毒和无毒化学品。
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Production of α-keto carboxylic acid dimers in yeast by overexpression of NRPS-like genes from Aspergillus terreus.通过过量表达土曲霉 NRPS 样基因在酵母中生产 α-酮羧酸二聚体。
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