海洋Moorena sp.蓝藻抗锥虫体脂肽Ukabamide的分离与全合成

IF 5 1区化学 Q1 CHEMISTRY, ORGANIC

Organic Letters Pub Date : 2025-01-24 DOI:10.1021/acs.orglett.4c04832

Masahiro Hagihara, Naoaki Kurisawa, Arihiro Iwasaki, Raimu Taguchi, Ghulam Jeelani, Tomoyoshi Nozaki, Kiyotake Suenaga

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引用次数: 0

摘要

非洲人类锥虫病是被忽视的热带病中最致命的疾病之一。虽然发现一种新的抗锥虫药物是非常需要的，但创造一种优越的先导化合物是具有挑战性的。本文报道了从海洋Moorena sp.蓝藻中分离到的ukabamide(1)作为一种选择性和有效的抗锥虫体脂肽（对布氏罗得西亚锥虫的IC50 = 34±18 nM）。通过光谱分析和降解反应对其结构进行了表征，并用全合成法对其结构进行了证实。此外，我们制备了两个修饰的类似物，并揭示了脂肪酸链长度对生物活性的重要性。这些发现可能为抗锥虫药物的设计提供指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Isolation and Total Synthesis of Ukabamide, an Antitrypanosomal Lipopeptide from a Marine Moorena sp. Cyanobacterium

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Isolation and Total Synthesis of Ukabamide, an Antitrypanosomal Lipopeptide from a Marine Moorena sp. Cyanobacterium

Human African trypanosomiasis (HAT) is one of the most lethal of the neglected tropical diseases. While the discovery of a novel antitrypanosomal drug is highly desired, the creation of a superior lead compound is challenging. Herein we report ukabamide (1), which was isolated from a marine Moorena sp. cyanobacterium, as a selective and potent antitrypanosomal lipopeptide (IC₅₀ = 34 ± 18 nM against Trypanosoma brucei rhodesiense). Its structure was elucidated by spectroscopic analyses and degradation reactions and confirmed by total synthesis. In addition, we prepared two modified analogs and revealed the importance of the fatty acid chain length for biological activity. These findings may provide design guidelines for an antitrypanosomal drug.

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来源期刊

Organic Letters 化学-有机化学

CiteScore

9.30

自引率

11.50%

发文量

1607

审稿时长

1.5 months

期刊介绍： Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.