Two new p-terphenyl derivatives (1, 2), together with six known ones (3 - 8), have been isolated from the marine fungal strain Aspergillus sp. AF119. The structures for terphyl acid (1) and terphyl diacid (2) were determined on the basis of HR Q-TOF-MS, and 1D- and 2D-NMR spectroscopic data. The in vitro cytotoxic activities of compounds 1 – 8 were tested against human tumor cell lines HeLa, HepG-2 and MDA-MB-435; only compounds 5 – 8 exhibited inhibitory activity against the tested cell lines with IC50 values < 20 μM. Moreover, compound 5 showed a mechanism of inducing cell cycle arrest and apoptosis mediated by the generation of ROS and subsequent DNA double-strand break.
IsaoK., AyakoH., NobusukeK, and YangC.S. (1989) New sesqui-neolignan from the pericarps of Illicium macranthum [J]. Chemical and Pharmaceutical Bulletin, 37, 1291–1292.
3.
IsaoK., TakuyaM., YumikoH, and YangC.S. (1991) Two new sesquineolignans from the bark of Illicium dunnianum. Chemical and Pharmaceutical Bulletin, 39, 2606–2608.
4.
IsaoK., ChifumiI., YukiK., TakashiT, and YangC.S. (1994) A new triphenyl-type neolignan and a biphenylneolignan from the bark of Illicium simonsii. Chemical and Pharmaceutical Bulletin, 42, 112–114.
5.
KohnoH., TakabaK., FukaiT, and NomuraT. (1987) Structure of mulberrofuran r, a novel 2-arylbenzofuran derivative from the cultivated mulberry tree (Morus lhou Koidz.). Heterocycles, 26, 759–762.
6.
GillM., SteglichW. (1987) Pigments of fungi (macromycetes). Fortschritte der Chemie Organischer Naturstoffe, 51, 1–317.
7.
YunB.S., LeeI.K., KimJ.P., YooI.D. (2000) Curtisians a-d, new free radical scavengers from the mushroom Paxillus curtisii. The Journal of Antibiotics, 53, 114–122.
8.
QuangD.N., HashimotoT., NukadaM., YamamotoI., TanakaM., AsakawaY. (2003) Curtisians e-h: Four p-terphenyl derivatives from the inedible mushroom Paxillus curtisii. Phytochemistry, 64, 649–654.
9.
QuangD.N., HashimotoT., NukadaM., YamamotoI., TanakaM., AsakawaY. (2003) Curtisians m-q: Five novel p-terphenyl derivatives from the mushroom Paxillus curtisii. Chemical and Pharmaceutical Bulletin, 51, 1064–1067.
10.
QuangD.N., HashimotoT., NukadaM., YamamotoI., HitakaY., TanakaM., AsakawaY. (2003) Thelephantins a, b and c: Three benzoyl p-terphenyl derivatives from the inedible mushroom Thelephora aurantiotincta. Phytochemistry, 62, 109–113.
11.
QuangD.N., HashimotoT., HitakaY., TanakaM., NukadaM., YamamotoI., AsakawaY. (2003) Thelephantins d–h: Five p-terphenyl derivatives from the inedible mushroom Thelephora aurantiotincta. Phytochemistry, 63, 919–924.
QuangD.N., HashimotoT., NukadaM., YamamotoI., TanakaM., AsakawaY. (2003) Antioxidant activity of curtisians i-l from the inedible mushroom Paxillus curtisii. Planta Medica, 69, 1063–1066.
14.
LeeI.K., YunB.S., KimJ.P., RyooI.J., KimY.H., YooI.D. (2003) Neuroprotective activity of p-terphenyl leucomentins from the mushroom paxillus panuoides. Bioscience, Biotechnology, and Biochemistry, 67, 1813–1816.
15.
ToshiyukiK., RyujiS., KazuoN., YoshimiK., YukioY., KeisukeM., HiroyoshiT., YasuoT., KikuoI., RyujiS., KenzoK., HiroshiN., YujiI, and YoshihiroT. (1998) Terprenins, novel immunosuppressants produced by Aspergillus candidus. The Journal of Antibiotics, 51, 445–450.
16.
KimJ.H., LeeJ.S., SongK.S., KwonC.S., KimY.K., KimJ.S. (2004) Polyozellin isolated from polyozellus multiplex induces phase 2 enzymes in mouse hepatoma cells and differentiation in human myeloid leukaemic cell lines. Journal of Agricultural and Food Chemistry, 52, 451–455.
17.
SteadP., AffleckK., SidebottomP.J., TaylorN.L., DrakeC.S., ToddM., JowettA., WebbG. (1999) Isolation and characterisation of a prenylated p-terphenyl metabolite of Aspergillus candidus possessing potent and selective cytotoxic activity; studies on mechanism of action. The Journal of Antibiotics, 52, 89–95.
18.
CaiS., SunS., ZhouH., KongX., ZhuT., LiD., GuQ. (2011) Prenylated polyhydroxy-p-terphenyls from Aspergillus taichungensis zhn-7-07. Journal of Natural Products, 74, 1106–1110.
19.
MarchelliR., ViningL.C. (1975) Terphenyllin, a novel p-terphenyl metabolite from Aspergillus candidus. The Journal of Antibiotics, 28, 328–331.
20.
KurobaneI., ViningL.C., McInnesA.G., SmithD.G. (1979) 3-Hydroxyterphenyllin, a new metabolite of Aspergillus candidus. Structure elucidation by 1H- and C-nuclear magnetic resonance spectroscopy. The Journal of Antibiotics, 32, 559–564.
21.
KobayashiA., TakemotoA. (1985) P-terphenyls with cytotoxic activity toward sea urchin embryos. Agricultural Biology and Chemistry, 49, 867–868.
22.
KobayashiA., TakemuraA., KoshimizuK., NaganoH., KawazuK. (1982) Candidusin a and b: New p-terphenyls with cytotoxic effects on sea urchin embryos. Agricultural Biology and Chemistry, 46, 585–589.
23.
HuangY., WangJ., LiG., ZhengZ., SuW. (2001) Antitumor and antifungal activities in endophytic fungi isolated from pharmaceutical plants Taxus mairei, Cephalataxus fortunei and Torreya grandis. FEMS Immunology and Medical Microbiology, 31, 163–167.
24.
MosmannT. (1983) Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65, 55–63.
25.
HancockJ.T., DesikanR, and NeillS.J. (2001) Role of reactive oxygen species in cell signalling pathways. Biochemical Society Transactions, 29, 345–349.
26.
BurmaS., ChenB.P., MurphyM., KurimasaA., ChenD.J. (2001) Atm phosphorylates histone h2ax in response to DNA double-strand breaks. The Journal of Biological Chemistry, 276, 42462–42467.
27.
BeckmanK.B., AmesB.N. (1997) Oxidative decay of DNA. The Journal of Biological Chemistry, 272, 19633–19636.
28.
CarmichaelJ., DeGraffW.G., GazdarA.F., MinnaJ.D., MitchellJ.B. (1987) Evaluation of a tetrazolium-based semiautomated colorimetric assay: Assessment of chemosensitivity testing. Cancer Research, 47, 936–942.
29.
WangJ., ZhaoB., ZhangW., WuX., WangR., HuangY., ChenD., ParkK., WeimerB.C., ShenY. (2010) Mycoepoxydiene, a fungal polyketide, induces cell cycle arrest at the g2/m phase and apoptosis in Hela cells. Bioorganic and Medicinal Chemistry Letters, 20, 7054–7058.
30.
OhtsukiT., KoyanoT., KowithayakornT., YamaguchiN., IshibashiM. (2004) Isolation of austroinulin possessing cell cycle inhibition activity from Blumea glomerata and revision of its absolute configuration. Planta Medica, 70, 1170–1173.
31.
LebelC.P., IschiropoulosH., BondyS.C. (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chemical Research in Toxicology, 5, 227–231.
