Ansellone J, a Potent in Vitro and ex Vivo HIV‑1 Latency Reversal Agent Isolated from a Phorbas sp. Marine Sponge

Five new minor sesterterpenoids, ansellones H (4), I (5), J (6), and K (7) and phorone C (8), have been isolated from a Phorbas sp. marine sponge collected in British Columbia. Their structures have been elucidated by detailed analysis of NMR and MS data. Ansellone J (6) and phorone C (8) are potent in vitro HIV-1 latency reversal agents that are more potent than the reference compound and control protein kinase C activator prostratin (3). The most potent Phorbas sesterterpenoid, ansellone J (6), was evaluated for HIV latency reversal in a primary cell context using CD4+ T cells obtained directly from four combination antiretroviral therapy-suppressed donors with HIV. To a first approximation, ansellone J (6) induced HIV latency reversal at levels similar to prostratin (3) ex vivo, but at a 10-fold lower concentration.