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.
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).
Department of Chemistry and Biochemistry, University of California , Santa Cruz, California 95064, United States.
Eric J
EJ
Mejia
Steven T
ST
Loveridge
George
G
Stepan
Angela
A
Tsai
Gregg S
GS
Jones
Tiffany
T
Barnes
Kimberly N
KN
White
Marija
M
Drašković
Karen
K
Tenney
Manuel
M
Tsiang
Romas
R
Geleziunas
Tomas
T
Cihlar
Nikos
N
Pagratis
Yang
Y
Tian
Helen
H
Yu
Phillip
P
Crews
D001203:Ascomycota / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology; D018942:Macrolides / Q000737:chemistry / Q000494:pharmacology*; D008386:Marine Biology; D008954:Models, Biological; D015394:Molecular Structure; D017735:Virus Latency / Q000187:drug effects
D001688:Biological Products; D056572:Histone Deacetylase Inhibitors; D007783:Lactones; D018942:Macrolides; C035359:monorden