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

Abstract

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 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 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.

Diversity and Ecology of Marine Algicolous Arthrinium Species as a Source of Bioactive Natural Products

“…As described in Table 2, it exhibited higher activities than the positive control (ascorbic acid), which corresponds to the result of a previous report [44]. Gentisyl alcohol has also been reported to have proangiogenic, caspase inhibition, histone deacetylases inhibition, antibacterial (against methicillin-resistant Staphylococcus aureus ), antifungal (against Colletotrichum gloeosporioides ), antileishmanial (against Leishmania donovani ), and cytotoxic (against human breast and colon cancer cell lines, MCF-7 and HT-29, respectively, and against sea urchin Strongylocentrotus intermedius ) activity [45,46,47,48,49,50,51,52,53]. This is the first report of the production of gentisyl alcohol from the genus Arthrinium .…”

Copper‐Catalyzed One‐Pot Synthesis of Dibenzofurans, Xanthenes, and Xanthones from Cyclic Diphenyl Iodoniums

“…Cyclic heteroatom containing compounds are commonly found in pharmaceuticals, and a variety of methods have been established to obtain these important structures. Among these heterocyclic compounds, oxygenated heterocyclic dibenzofurans and xanthones are privileged scaffolds in many pharmaceutically active compounds, such as eriobofuran, vialinin B, griseoxanthone C, and α‐mangostin (Figure ) . Xanthene derivatives are another special class of oxygen‐incorporating tricyclic compounds, demonstrating impressive photophysical property arising from their π‐conjugation systems, used as common building blocks of dyes and fluorescent materials .…”

Ent-homocyclopiamine B, a Prenylated Indole Alkaloid of Biogenetic Interest from the Endophytic Fungus Penicillium concentricum

“…Penicillium concentricum , the endophytic fungus used in this study was isolated from healthy liverwort Trichocolea tomentella and identified as previously described [1].…”

“…This adaptation makes endophytes capable to produce wide range of compounds when isolated from the host and fermented using various media. Compounds exhibiting antimicrobial, antiviral and antiproliferative activity have been reported from endophytes [1]. We recently described chemical and pharmacological investigations of extracts prepared from a Penicillium (Trichocomaceae) fungus endophytic to the liverwort Trichocolea tomentella (Trichocoleaceae) that led to the isolation of the antifungal griseofulvin, dehydrogriseofulvin, dechlorogriseofulvin, dehydrodechlorogriseofulvin, griseophenones B and C, griseoxanthones, driniopsin H, norlichexanthonealternariol, ethylene glycol benzoate, 6-chloro-3,8-dihydroxy-1-methylxanthone, epi -epoxydon, gentisyl alcohol, gentisyl quinone, hydroxychlorogentisyl quinone, chlorogentisyl quinone, bromogentisyl alcohol and the identification of compounds exhibiting antiproliferative activity against hormone-dependent breast cancer cell line (MCF-7) and the human colorectal adenocarcinoma cell line HT-29.…”