Bioactive components from Psorothamnus junceus and Pseudophegopteris subaurita, and structure-activity relationship study of cytotoxic p-quinols

摘要

The objective of the present study was to find novel and potent antitumor compounds in higher plants. The extracts of the roots and stem barks of Psorothamnus junceus showed significant cytotoxic activity in human tumor cytotoxicity bioassays during the broad screening of plant extracts. Bioactivity-directed isolation of P. junceus yielded 11 compounds. Six are new natural compounds. Psorothamnone A and B are novel heterocyclic compounds isolated from the stem-barks of P. junceus. They exhibited inhibitory activities against protein kinase C. In addition, two novel isoflavonoid-type compounds, PJ-HZ-I-57 and PJ-HZ-I-68, with a unique p-quinol (4-hydroxy-2,5-cyclohexadienone) functional group were isolated from the roots of P. junceus. These two compounds demonstrated high cytotoxicity against solid tumor cell lines in the NCI human tumor cell line panels. The extracts of the leaves of Pseudophegopteris subaurita were also subjected to bioactivity-directed fractionation and isolation. Six compounds were isolated. One is a new compound. Protogenkwanone, a known flavonoid-type quinol showed strong activity in the NCI human tumor cell line panels. Preliminary structure-activity relationship studies have demonstrated that the 4-hydroxy-2,5-cyclohexadienone moiety is the essential functional group for the cytotoxic p-quinol compounds. More than 20 simple p-quinols were therefore synthesized to evaluate their cytotoxicity against human tumor cell lines. A mechanistic study using N-acetylcysteine as a model was performed.