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).
Four new compounds, (−)-petrosynoic acids A–D (1–4), and five known congeners, pellynols A (5), C (6), D (7), F (8), and I (9) were isolated from a Petrosia sp. marine sponge collected in American Samoa. Isolation work was guided by cytotoxicity against human lung cancer cells (H460). The structures of the C31-C33 polyacetylenes (1–9) were determined on the basis of 1D- and 2D-NMR analysis, mass spectrometry, and comparison of specific rotation values. Compounds 1–9 were found to be broadly cytotoxic with limited selectivity for cancer cells as they were all moderately active against the A2058 (melanoma), H522-T1 (lung), and H460 (lung) human cancer cell lines as well as IMR-90 quiescent human fibroblast cells.
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