First Total Synthesis and Structure–Activity Relationship of Iheyamide A, an Antitrypanosomal Linear Peptide Isolated from a Dapis sp. Marine Cyanobacterium,Journal of Natural Products

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First Total Synthesis and Structure–Activity Relationship of Iheyamide A, an Antitrypanosomal Linear Peptide Isolated from a Dapis sp. Marine Cyanobacterium
Journal of Natural Products ( IF 3.3 ) Pub Date : 2021-09-06 , DOI: 10.1021/acs.jnatprod.1c00792
Arihiro Iwasaki ₁ , Kazuya Teranuma ₁ , Naoaki Kurisawa ₁ , Yulia Rahmawati ₂ , Ghulam Jeelani ₂ , Tomoyoshi Nozaki ₂ , William H Gerwick _{3,

4} , Kiyotake Suenaga ₁

Affiliation

Iheyamide A (1) is an antitrypanosomal linear peptide isolated from a Dapis sp. marine cyanobacterium by our group in 2020, and based on structure–activity relationships of its natural analogues, the C-terminal pyrrolinone moiety has been identified as the phamacophore for its antiparasitic activity. Further, we isolated this pyrrolinone moiety by itself as a new natural product from the marine cyanobacterium and named it iheyanone (2). As expected, iheyanone (2) showed antitrypanosomal activity, but its potency was weaker than iheyamide A (1). To clarify more detailed structure–activity relationships, we completed a total synthesis of iheyamide A (1) along with iheyanone (2) and evaluated the antitrypanosomal activities of several synthetic intermediates. As a result, we found that the longer the peptide chain, the stronger the antitrypanosomal activity. As iheyamide A (1) showed selective toxicity against Trypanosoma brucei rhodesiense, these findings can provide design guidelines for antitrypanosomal drugs.

中文翻译：

Iheyamide A 的首次全合成和结构-活性关系，一种从 Dapis sp. 中分离的抗锥虫线性肽。海洋蓝藻

Iheyamide A ( 1 ) 是一种从Dapis sp. 中分离的抗锥虫线性肽。我们小组在 2020 年发现了海洋蓝藻，根据其天然类似物的结构-活性关系，C 端吡咯啉酮部分已被确定为具有抗寄生虫活性的药效团。此外，我们从海洋蓝藻中分离出这种吡咯啉酮部分作为一种新的天然产物，并将其命名为 iheyanone ( 2 )。正如预期的那样，iheyanone ( 2 ) 显示出抗锥虫活性，但其效力比 iheyamide A ( 1 )弱。为了阐明更详细的构效关系，我们完成了 iheyamide A ( 1 ) 和 iheyanone (2 ) 并评估了几种合成中间体的抗锥虫活性。结果，我们发现肽链越长，抗锥虫活性越强。由于 iheyamide A ( 1 ) 对罗得西亚布氏锥虫显示出选择性毒性，因此这些发现可为抗锥虫药物的设计提供指导。

更新日期：2021-09-24

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