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从红树林内生真菌 DHS-48 中分离得到的免疫抑制细胞松弛素。

Immunosuppressive Cytochalasins from the Mangrove Endophytic Fungus DHS-48.

机构信息

School of Chemical Engineering and Technology, Hainan University, Haikou 570228, China.

出版信息

Mar Drugs. 2022 Aug 18;20(8):526. doi: 10.3390/md20080526.

DOI:10.3390/md20080526
PMID:36005528
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9409992/
Abstract

Three new cytochalasins, phomoparagins A-C (-), along with five known analogs (-), were isolated from DHS-48, a mangrove-derived endophytic fungus. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD techniques. Notably, possessed an unprecedented 5/6/5/8/5-fused pentacyclic skeleton. These compounds were tested for their inhibitory activity against concanavalin A (ConA)/lipopolysaccharide (LPS)-induced spleen lymphocyte proliferation and calcineurin (CN) enzyme. Several metabolites ( and -) exhibited fascinating inhibitory activities with a relatively low toxicity. Furthermore, was demonstrated to inhibit ConA-stimulated activation of NFAT1 dephosphorylation and block NFAT1 translocation in vitro, subsequently inhibiting the transcription of interleukin-2 (IL-2). Our results provide evidence that may, at least partially, suppress the activation of spleen lymphocytes via the CN/NFAT signaling pathway, highlighting that it could serve as an effective immunosuppressant that is noncytotoxic and natural.

摘要

从红树林内生真菌 DHS-48 中分离得到三个新的细胞松弛素，即 phomoparagins A-C(-)，以及五个已知类似物(-)。采用详细的 HRESIMS、NMR 和 ECD 技术相结合的方法，阐明了它们的结构，包括绝对构型。值得注意的是，具有前所未有的 5/6/5/8/5-稠合的五环骨架。测试了这些化合物对刀豆蛋白 A (ConA)/脂多糖 (LPS) 诱导的脾淋巴细胞增殖和钙调神经磷酸酶 (CN) 酶的抑制活性。几种代谢产物（和-）表现出令人着迷的抑制活性，且毒性相对较低。此外，证实 可抑制 ConA 刺激的 NFAT1 去磷酸化和阻断 NFAT1 在体外的易位，从而抑制白细胞介素-2 (IL-2) 的转录。我们的结果表明，至少部分抑制了脾淋巴细胞的激活通过 CN/NFAT 信号通路，突出表明它可以作为一种有效的免疫抑制剂，非细胞毒性和天然。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/3fa6285f3c24/marinedrugs-20-00526-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/25adbf9d6a3f/marinedrugs-20-00526-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/3ee1e13e2c00/marinedrugs-20-00526-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/6d41f7aa849a/marinedrugs-20-00526-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/3d0648de756c/marinedrugs-20-00526-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/5b0feeb926e5/marinedrugs-20-00526-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/70f58289393a/marinedrugs-20-00526-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/3fa6285f3c24/marinedrugs-20-00526-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/25adbf9d6a3f/marinedrugs-20-00526-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/3ee1e13e2c00/marinedrugs-20-00526-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/6d41f7aa849a/marinedrugs-20-00526-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/3d0648de756c/marinedrugs-20-00526-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/5b0feeb926e5/marinedrugs-20-00526-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/70f58289393a/marinedrugs-20-00526-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17f5/9409992/3fa6285f3c24/marinedrugs-20-00526-g007.jpg

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