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.