Caryophyllene Sesquiterpenes from the Marine-Derived Fungus Ascotricha sp ZJ-M-5 by the One Strain-Many Compounds Strategy

The marine-derived fungus Ascotricha sp. ZJ-M-5, which can produce cyclonerodiol analogues, a 3,4-seco lanostane triterpenoid, and diketopiperazines in an eutrophic medium, was subjected to a one strain many compounds (OSMAC) analysis. It was found to produce three new caryophyllene derivatives (1-3) and the known 1,3,6-trihydroxy-8-methylxanthone (4) in an oligotrophic medium, Czapek Dox broth with or without Mg2+. (+)-6-O-Demethylpestalotiopsin A (1) and (+)-6-O-demethylpestalotiopsin C (2), which have a five-membered hemiacetal structural moiety, showed growth inhibitory effects against HL-60 and K562 leukemia cell lines with the lowest GI(50) value of 6.9 +/- 0.4 mu M. It can be concluded that modification of the culture media is still effective in the discovery of novel bioactive fungal secondary metabolites.