Ichthyotoxic phloroglucinol derivatives from Dryopteris fragrans and their anti-tumor promoting activity.
Two new ichthyotoxic compounds, aspidin PB (8) and dryofragin (9), along with three known phloroglucinol derivatives (1-3) and five terpenoids, were isolated from the whole herbs of Dryopteris fragrans by toxicity-directed fractionation using Oryzias latipes (Japanese name; medaka). The structures of the new compounds were determined by spectroscopic methods including 2D NMR techniques. Amongst the isolates, aspidin PB (8), dryofragin (9), and 1-5 exhibited potent ichthyotoxic activity against medaka with a median tolerance limit (TLm after 24 h) of 1.2-4.3 microg/ml. These compounds which are toxic to fish also had a potent inhibitory effect on the activation of Epstein-Barr virus early-antigen (EBV-EA) induced by tetradecanoyl phorbol 13-acetate, which is an in vitro short-term assay for anti-tumor promoting agents. Aspidin BB (2) and albicanol (4), which exhibited strong inhibitory effects on the EBV-EA activation, significantly suppressed an in vivo two-stage carcinogenesis on mouse skin.
Ito
H
H
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Japan.
Muranaka
T
T
Mori
K
K
Jin
Z X
ZX
Tokuda
H
H
Nishino
H
H
Yoshida
T
T
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002460:Cell Line; D003512:Cyclohexanones / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D004854:Herpesvirus 4, Human / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008813:Mice, Inbred ICR; D009990:Oryzias; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D010944:Plants / Q000737:chemistry*
D016588:Anticarcinogenic Agents; D003512:Cyclohexanones; C000602150:aspidin PB; D010696:Phloroglucinol