Spongian Diterpenoids Derived from the Antarctic Sponge Dendrilla antarctica Are Potent Inhibitors of the Leishmania Parasite.
Spongian Diterpenoids Derived from the Antarctic Sponge Dendrilla antarctica Are Potent Inhibitors of the Leishmania Parasite.
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DOI：
10.1021/acs.jnatprod.0c00025
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发表时间：
2020-05-22
影响因子：
5.1
通讯作者：
Baker BJ
中科院分区：
文献类型：
--
作者：
Shilling AJ;Witowski CG;Maschek JA;Azhari A;Vesely BA;Kyle DE;Amsler CD;McClintock JB;Baker BJ
从南极海绵Dendrilla anapartica的CH 2Cl 2提取物中，我们利用CH 2Cl 2/MeOH提取方案发现了海绵二萜，包括先前报道的四氢黄芪硫素（1），四氢黄芪硫素-1（2），膜萜（3）和达尔文萜（4）。然而，提取物也产生了带有一个或多个甲缩醛官能团的二萜（5-9），其中两个是以前未报道的，而其他的在这里进行了修订。对二萜反应性的进一步研究产生了额外的新代谢物（10-12），这些代谢物以及甲基缩醛被鉴定为来自黄芪硫苷甲醇分解的人工产物。针对针对杜氏利什曼原虫感染的J774A.1巨噬细胞的活性，评估甲醇分解产物类膜A-H（5-12）以及天然产物1-4的生物活性，揭示了对它们的结构/活性关系的了解。四个二萜类化合物，四氢青蒿素sulphurin-1（2）以及膜状化合物B（6）、D（8）和G（11），对L. donovani对未感染的J774A.1细胞没有明显的细胞毒性。利什曼病是一种被忽视的热带疾病，每年影响100万人，如果不及时治疗可能致命。
From the CH2Cl2 extract of the Antarctic sponge Dendrilla antarctica we found spongian diterpenes, including previously reported aplysulphurin (1), tetrahydroaplysulphurin-1 (2), membranolide (3), and darwinolide (4), utilizing a CH2Cl2/MeOH extraction scheme. However, the extracts also yielded diterpenes bearing one or more methyl acetal functionalities (5–9), two of which are previously unreported, while others are revised here. Further investigation of diterpene reactivity led to additional new metabolites (10–12), which identified them as well as the methyl acetals as artifacts from methanolysis of aplysulphurin. The bioactivity of the methanolysis products, membranoids A–H (5–12), as well as natural products 1–4, were assessed for activity against Leishmania donovani-infected J774A.1 macrophages, revealing insights into their structure/activity relationships. Four diterpenes, tetrahydroaplysulphurin-1 (2) as well as membranoids B (6), D (8), and G (11), displayed low micromolar activity against L. donovani with no discernible cytotoxicity against uninfected J774A.1 cells. Leishmaniasis is a neglected tropical disease that affects one million people every year and can be fatal if left untreated.
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影响因子：
4.4
作者：
van Griensven, Johan;Diro, Ermias
通讯作者：
Diro, Ermias
影响因子：
4.2
作者：
Kanwar, Ankush;Eduful, Benjamin J.;Leahy, James W.
通讯作者：
Leahy, James W.
影响因子：
5.4
作者：
Demers, Danielle H.;Knestrick, Matthew A.;Baker, Bill J.
通讯作者：
Baker, Bill J.
影响因子：
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作者：
Hooft RW;Straver LH;Spek AL
通讯作者：
Spek AL
影响因子：
1.1
作者：
KARUSO, P;SKELTON, BW;WHITE, AH
通讯作者：
WHITE, AH