甘油类似物的潜在杀锥虫活性

IF 2.5 4区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
R. A. Humann, T. K. Smith
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引用次数: 0

摘要

甘油是一种用途广泛、无处不在的化合物,在原核生物和真核生物的大量代谢途径中发挥着重要作用。除了治疗潜力外,以前还探索过相对较少的甘油类似物作为甘油激酶抑制剂的用途,但它们作为(原)药物在锥虫病等寄生虫病中的用途却未见报道。有关甘油代谢,特别是甘油与水杨羟肟酸(SHAM)在布氏锥虫体内的协同抗寄生行为的文献非常广泛。然而,甘油类似物作为可能的优质组合化合物的用途尚未得到探讨。本报告介绍了各种甘油类似物的合成及其随后的生化嗜型分析,以了解其对脂质代谢的影响及其与 SHAM 对布氏锥虫可能具有的协同活性。甘油类似物会导致形态变化,包括鞭毛脱落、细胞分裂缺陷和 "大眼 "表型。这四种化合物联合使用对布氏锥虫的毒性要么与 SHAM 相当,要么略有增加。不过,这些化合物与 SHAM 之间主要是拮抗关系,而不是协同作用。这项研究强调了小分子甘油类似物与 SHAM 联用治疗寄生虫病(如锥虫病)的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Potential Trypanocidal Activity of Glycerol Analogues

Potential Trypanocidal Activity of Glycerol Analogues
Glycerol, a versatile and ubiquitous compound, plays a vital role in a plethora of metabolic pathways in both prokaryotes and eukarotyes. Relatively few glycerol analogues have previously been explored for their use as glycerol kinase inhibitors, in addition to their therapeutic potential, however their use as (pro)‐drugs in the context of parasitic diseases such as trypanosomiasis is unreported. The literature on glycerol metabolism and particular its synergic anti‐profilation behaviour with salicylhydroxamic acid (SHAM) in Trypanosoma brucei is extensive. However, utiliation of glycerol analogues has not been explored as possible superior combinatory compounds. This report describes the synthesis of various glycerol analogues and their subsequent biochemical pheotypic analysis for their effect on lipid metabolism and their possible synergic activity with SHAM on Trypanosoma brucei. The glycerol analogues caused morphological changes;, including detached flagella, cytokinesis defects and ‘big‐eye’ phenotype. All four compounds either matched or marginally increased the toxicity of SHAM when used in combination against Trypanosoma brucei. However, the compounds exhibited mostly an antagonistic relationship with SHAM rather than synergistic. This research highlights the potential of small molecule glycerol analogues for their combination use with SHAM for the treatment of parasitic disease, such as trypanosomiasis.
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来源期刊
ChemistryOpen
ChemistryOpen CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
4.80
自引率
4.30%
发文量
143
审稿时长
1 months
期刊介绍: ChemistryOpen is a multidisciplinary, gold-road open-access, international forum for the publication of outstanding Reviews, Full Papers, and Communications from all areas of chemistry and related fields. It is co-owned by 16 continental European Chemical Societies, who have banded together in the alliance called ChemPubSoc Europe for the purpose of publishing high-quality journals in the field of chemistry and its border disciplines. As some of the governments of the countries represented in ChemPubSoc Europe have strongly recommended that the research conducted with their funding is freely accessible for all readers (Open Access), ChemPubSoc Europe was concerned that no journal for which the ethical standards were monitored by a chemical society was available for such papers. ChemistryOpen fills this gap.
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