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来自具有抗锥虫潜力的海洋细菌的饱和同型脂肪酸。

Saturated Iso-Type Fatty Acids from the Marine Bacterium with Anti-Trypanosomal Potential.

作者信息

Santos Ferreira Dayana Agnes, de Castro Levatti Erica Valadares, Santa Cruz Lucas Monteiro, Costa Alan Roberto, Migotto Álvaro E, Yamada Amanda Yaeko, Camargo Carlos Henrique, Christodoulides Myron, Lago João Henrique G, Tempone Andre Gustavo

机构信息

Pathophysiology Laboratory, Instituto Butantan, Av. Vital Brazil, 1500, Sao Paulo 05503-900, SP, Brazil.

Centre of Organic Contaminants, Instituto Adolfo Lutz, Av. Dr. Arnaldo, 355, Sao Paulo 01246-000, SP, Brazil.

出版信息

Pharmaceuticals (Basel). 2024 Apr 13;17(4):499. doi: 10.3390/ph17040499.

Abstract

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new anti-trypanosomal compounds, we investigated the potential of the metabolites from the bacteria living in the corals and sediments of the southeastern Brazilian coast. Three corals, , , and sediments yielded 11 bacterial strains that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera-, , , , and To conduct this study, EtOAc extracts were prepared and tested against The crude extracts showed IC values ranging from 15 to 51 μg/mL against the trypomastigotes. The bacterium was selected for fractionation, resulting in an active fraction (FII) with IC values of 17.7 μg/mL and 23.8 μg/mL against the trypomastigotes and amastigotes, respectively, with neither mammalian cytotoxicity nor hemolytic activity. Using an NMR and ESI-HRMS analysis, the FII revealed the presence of unsaturated iso-type fatty acids. Its lethal action was investigated, leading to a protein spectral profile of the parasite altered after treatment. The FII also induced a rapid permeabilization of the plasma membrane of the parasite, leading to cell death. These findings demonstrate that these unsaturated iso-type fatty acids are possible new hits against

摘要

恰加斯病是一种治疗方法有限且效果不佳的被忽视热带病。为了寻找新的抗锥虫化合物,我们研究了生活在巴西东南海岸珊瑚和沉积物中的细菌所产生代谢物的潜力。三种珊瑚,[具体珊瑚名称1]、[具体珊瑚名称2]和[具体珊瑚名称3]以及沉积物分离出了11株细菌菌株,通过基质辅助激光解吸电离飞行时间质谱(MALDI-ToF/MS)或基因测序对其进行了完全鉴定,结果得到六个属,[具体属名1]、[具体属名2]、[具体属名3]、[具体属名4]、[具体属名5]和[具体属名6]。为开展本研究,制备了乙酸乙酯提取物并针对[具体对象]进行测试。粗提物对锥鞭毛体的半数抑制浓度(IC)值范围为15至51μg/mL。选择[具体细菌名称]进行分离,得到一种活性组分(FII),其对锥鞭毛体和无鞭毛体的IC值分别为17.7μg/mL和23.8μg/mL,且对哺乳动物无细胞毒性和溶血活性。通过核磁共振(NMR)和电喷雾高分辨质谱(ESI-HRMS)分析,FII显示存在不饱和异型脂肪酸。对其致死作用进行了研究,结果表明处理后寄生虫的蛋白质谱发生了改变。FII还诱导寄生虫的质膜迅速通透化,导致细胞死亡。这些发现表明,这些不饱和异型脂肪酸可能是对抗[具体对象]的新的有效物质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2af0/11053438/d7069b0521c2/pharmaceuticals-17-00499-g001.jpg

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