ABSTRACT
The purpose of current study is to investigate the metabolic profile of a triptolide derivative (5R)-5-hydroxytriptolide in vitro. (5R)-5-Hydroxytriptolide was incubated with the hepatocytes of human, monkey, dog, rat or mouse, respectively. Compared with inactivated hepatocytes, four metabolites were identified in hepatocytes from all five species: oxidative ring-opening metabolite (M1), glutathione-conjugating metabolite (M2), and monooxidative combined with glutathione-conjugating metabolites (M3-1 and M3-2), respectively. In human or rat liver microsomes, seven metabolites of (5R)-5-hydroxytriptolide were found, dehydrogenated metabolite (M4) and monooxidative metabolites (M5-1–M5-6), respectively. Reference standards for the metabolites were obtained either through chemical semisynthesis or biotransformation through rat primary hepatocytes. The structures of five metabolites were confirmed, which were 12,13-epoxy ring-opening metabolite M1, 12-glutathione-conjugating metabolite M2, (16S)-, (2R)- and (19R)-monohydroxylated metabolites M5-1, M5-4, and M5-5, respectively. In vitro activity assay revealed that only (2R)-hydroxylated metabolite exhibited weak immunosuppressive activity with less than one-tenth the activity of its parent drug, and a significant decrease in toxicity was observed. It is suggested that (5R)-5-hydroxytriptolide might undergo metabolic inactivation and detoxification in vivo.
ABSTRACT
The in vitro antitumor activity of bakuchiol was exploited, compared with tamoxifen. The result of biological activities showed that bakuchiol could inhibit human breast cancer and the IC50 values were 2.89 x 10(-5) mol L(-1) and 8.29 x 10(-3) mol L(-1) against the cells line T-47D and MDA-MB-231 respectively. On the other hand, the key intermediate to synthesize bakuchiol was obtained by the method of Ireland-Claisen rearrangement. Comparing with traditional Claisen rearrangement, the reaction conditions are milder and the reaction reagents are safer.
Subject(s)
Female , Humans , Antineoplastic Agents, Hormonal , Pharmacology , Antineoplastic Agents, Phytogenic , Pharmacology , Breast Neoplasms , Pathology , Cell Line, Tumor , Cell Proliferation , Inhibitory Concentration 50 , Phenols , Pharmacology , Plants, Medicinal , Chemistry , Psoralea , Chemistry , Tamoxifen , PharmacologyABSTRACT
To study the phenolic constituents from the dry stem of Juncus effusus L. , the constituents were isolated by normal-phase and reverse-phase silica gel column chromatography from the EtOAc extract. Their structures were elucidated by spectral analysis. Six phenolic constituents were purified and identified as 7-carboxy-2-hydroxy-1-methyl-5-vinyl-9,10-dihydrophenanthrene (1) , 2,3-isopylidene-1-O-ferulic acid glyceride ( 2 ) , ( 2S )-2, 3-isopylidene-1-0-p-coumaroyl glyceride (3 ) , dehydroeffusal ( 4 ) , p-hydroxybenzaldehyde (5) and luteolin-5,3'-dimethyl ether (6). Compounds 1 and 2 are new compounds. Compounds 5 and 6 were isolated from Juncaceae plant for the first time. 13C NMR data of compound 6 were reported for the first time.