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

详细信息    查看全文

• 作者：Eric J. Mejia ; Steven T. Loveridge ; George Stepan ; Angela Tsai ; Gregg S. Jones ; Tiffany Barnes ; Kimberly N. White ; Marija Dra拧kovi膰 ; Karen Tenney ; Manuel Tsiang ; Romas Geleziunas ; Tomas Cihlar ; Nikos Pagratis ; Yang Tian ; Helen Yu ; Phillip Crews
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：March 28, 2014
• 年：2014
• 卷：77
• 期：3
• 页码：618-624
• 全文大小：373K
• 年卷期：v.77,no.3(March 28, 2014)
• ISSN：1520-6025

文摘

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鈥揇 (5鈥?b>7). Compounds 1鈥?b>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 渭M) relative to the HDAC inhibitors apicidin (EC₅₀ = 0.3 渭M), romidepsin (EC₅₀ = 0.003 渭M), and SAHA (EC₅₀ = 0.6 渭M); however, it achieved equivalent maximum efficacy relative to the positive control compounds (98% of SAHA and romidepsin).