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研究来源于高温毁丝菌的海洋天然产物，包括雷西酸内酯，其能在中枢记忆 CD4+T 细胞的体外模型中重新激活潜伏的 HIV-1 表达。

Study of marine natural products including resorcyclic acid lactones from Humicola fuscoatra that reactivate latent HIV-1 expression in an in vitro model of central memory CD4+ T cells.

机构信息

Department of Chemistry and Biochemistry, University of California , Santa Cruz, California 95064, United States.

出版信息

J Nat Prod. 2014 Mar 28;77(3):618-24. doi: 10.1021/np400889x. Epub 2014 Feb 4.

DOI:10.1021/np400889x
PMID:24495105
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3993908/
Abstract

An extract of Humicola fuscoatra (UCSC strain no. 108111A) was shown to reactivate latent HIV-1 expression in an in vitro model of central memory CD4+ T cells. We report the bioassay-guided isolation and structure determination of several resorcyclic acid lactones, including four known compounds, radicicol (1, aka. monorden) and pochonins B (2), C (3), and N (4), and three new analogues, radicicols B-D (5-7). Compounds 1-3 and 5 showed moderate activities in the memory T cell model of HIV-1 latency. Radicicol (1) displayed lower potency in reactivating latent HIV-1 (EC50 = 9.1 μM) relative to the HDAC inhibitors apicidin (EC50 = 0.3 μM), romidepsin (EC50 = 0.003 μM), and SAHA (EC50 = 0.6 μM); however, it achieved equivalent maximum efficacy relative to the positive control compounds (98% of SAHA and romidepsin).

摘要

从 Humicola fuscoatra（UCSC 株号 108111A）中提取的物质，在体外模型中表现出重新激活潜伏 HIV-1 表达的作用，该模型为中央记忆 CD4+T 细胞。我们报告了生物测定指导的分离和结构确定几种雷杜辛内酯，包括四种已知化合物，雷杜辛（1，又名单端孢菌素）和 pochonins B（2）、C（3）和 N（4），以及三种新的类似物，radicicols B-D（5-7）。化合物 1-3 和 5 在 HIV-1 潜伏的记忆 T 细胞模型中表现出中等活性。雷杜辛（1）在重新激活潜伏 HIV-1 方面的效力低于组蛋白去乙酰化酶抑制剂 apicidin（EC50=0.3 μM）、romidepsin（EC50=0.003 μM）和 SAHA（EC50=0.6 μM）（EC50=9.1 μM）；然而，它相对于阳性对照化合物实现了等效的最大功效（98%的 SAHA 和 romidepsin）。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e78/3993908/d5d0be0363f3/np-2013-00889x_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e78/3993908/950e686d7b3b/np-2013-00889x_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e78/3993908/179321788875/np-2013-00889x_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e78/3993908/6829ce9a5f9a/np-2013-00889x_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e78/3993908/017294433e46/np-2013-00889x_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e78/3993908/d5d0be0363f3/np-2013-00889x_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e78/3993908/950e686d7b3b/np-2013-00889x_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e78/3993908/179321788875/np-2013-00889x_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e78/3993908/6829ce9a5f9a/np-2013-00889x_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e78/3993908/017294433e46/np-2013-00889x_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e78/3993908/d5d0be0363f3/np-2013-00889x_0006.jpg

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