Halogenated Compounds from Directed Fermentation of Penicillium concentricum, an Endophytic Fungus of the Liverwort Trichocolea tomentella

One new chlorinated xanthone, 6-chloro-3,8-dihydroxy-1-methylxanthone ( 1 ), a new 2-bromo-gentisyl alcohol ( 2 ), and a mixture of 6-epimers of 6-dehydroxy-6-bromogabosine C ( 3a and 3b ), together with 19 previously identified compounds, epoxydon ( 4 ), norlichexanthone ( 5 ), 2-chlorogentisyl alcohol ( 6 ), hydroxychlorogentisyl quinone ( 7 ), 6-dehydroxy-6α-chlorogabosine C ( 8a ), 6-dehydroxy-6β-chlorogabosine C ( 8b ), gentisyl alcohol ( 9 ), gentisyl quinone ( 10 ), ( R,S )-1-phenyl-1,2-ethanediol ( 11 ), dehydrodechlorogriseofulvin ( 12 ), dechlorogriseofulvin ( 13 ), dehydrogriseofulvin ( 14 ), griseofulvin ( 15 ), ethylene glycol benzoate ( 16 ), alternariol ( 17 ), griseoxanthone C ( 18 ), drimiopsin H ( 19 ), griseophenone C ( 20 ), and griseophenone B ( 21 ), were isolated from cultures of Penicillium concentricum, a fungal endophyte of the liverwort Trichocolea tomentella . The structures of the new compounds ( 1, 2, 3a, and 3b ) were elucidated by interpretation of spectroscopic data including one- and two-dimensional NMR techniques. Among these, compounds 2 – 4 displayed modest cytotoxicity to the MCF-7 hormone-dependent breast cancer cell line with IC 50 values of 8.4, 9.7, and 5.7 μM, respectively, whereas compound 9 exhibited selective cytotoxicity against the HT-29 colon cancer cell line with an IC 50 value of 6.4 μM. During this study we confirmed that the brominated gentisyl alcohol ( 2 ) was formed by chemical conversion of 4 during bromide salt addition to culture media.