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  3. 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

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

  • J Nat Prod. 2014 Mar 28;77(3):618-24. doi: 10.1021/np400889x.
Eric J Mejia 1,  Steven T Loveridge,  George Stepan,  Angela Tsai,  Gregg S Jones,  Tiffany Barnes,  Kimberly N White,  Marija Drašković,  Karen Tenney,  Manuel Tsiang,  Romas Geleziunas,  Tomas Cihlar,  Nikos Pagratis,  Yang Tian,  Helen Yu,  Phillip Crews
Affiliations

Affiliation

  • 1 Department of Chemistry and Biochemistry, University of California , Santa Cruz, California 95064, United States.
PMID: 24495105 DOI: 10.1021/np400889x
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).

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