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Cytotoxic Activities and Anti‐Tumor‐Promoting Effects of Microbial Transformation Products of Prenylated Chalcones from Angelica keiskei
Author(s) -
Akihisa Toshihiro,
Motoi Toshihiro,
Seki Akihito,
Kikuchi Takashi,
Fukatsu Makoto,
Tokuda Harukuni,
Suzuki Nobutaka,
Kimura Yumiko
Publication year - 2012
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201100255
Subject(s) - chemistry , prenylation , cytotoxic t cell , stereochemistry , tumor promotion , cytotoxicity , metabolite , hl60 , raji cell , in vivo , biochemistry , in vitro , carcinogenesis , biology , gene , microbiology and biotechnology , enzyme
Three prenylated chalcones, 4‐hydroxyderricin ( 1 ), xanthoangelol ( 2 ), and xanthoangelol F ( 3 ), isolated from Angelica keiskei , were transformed by the fungus Aspergillus saitoi. These chalcones were converted to flavanones ( i.e. , 4, 8 , and 12 ), and prenyl‐chain‐hydrated ( i.e. , 5, 7, 9 – 11 , and 13 ) and ring‐ B ‐hydroxylated ( i.e. , 6 ) chalcones. The structures of three new metabolites, 7, 9 , and 13 , were established as 2″,3″‐dihydro‐4,3″‐dihydroxyderricin, 6″,7″‐dihydro‐7″‐hydroxyxanthoangelol, and 6″,7″‐dihydro‐7″‐hydroxyxanthoangelol F, respectively. Upon evaluation of cytotoxic activities of compounds 1 – 13 , the metabolite 7 exhibited potent cytotoxicity against HL60 cells, and this cell death was revealed to be mostly due to apoptosis. In addition, compounds 1 – 4, 7 – 10, 12 , and 13 were examined for their inhibitory effects on the induction of EpsteinBarr virus early antigen (EBV‐EA) by 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cells. All compounds tested showed inhibitory effects against EBV‐EA activation with potencies higher than that of β ‐carotene. Furthermore, the metabolite 13 exhibited inhibitory effect on skin tumor promotion in an in vivo two‐stage mouse skin carcinogenesis test based on 7,12‐dimethylbenz[ a ]anthracene (DMBA) as initiator, and with TPA as promoter.