Coompo Research Chemicals

Since Pd-II [(+)anomalin, (+)praeruptorin B], a seselin-type coumarin, was found to inhibit tumor promoter induced phemonenon in vitro, the effect of Pd-II on the in vivo tumorpromoting action of 12-O-tetradecanoylphorbol-13-acetate (IPA) in 7,12-dimethylbenz [a] anthracene-initiated mouse skin was investigated. Pd-II, applied 40 min before the TPA treatment, at a dose of 10 μmol/painting, completely suppressed tumor formation up to 20 weeks of tumor promotion, without any toxicity. Besides Pd-II, various antitumor-promoter coumarins were found in the traditional Chinese medicine Qian-Hu, from which Pd-II was obtained. These coumarins may be useful for the development of an effective method to prevent cancer.

As a part of a systematic pharmacokinetic evaluation of the herb in our laboratory, the present study investigated, for the first time, the metabolic profile of (+)-praeruptorin B (dPB) and (+)-praeruptorin E (dPE), two main bioactive constituents of Peucedani Radix in pooled liver microsomes of rats (RLMs) and humans (HLMs). dPE was eliminated faster than dPB in both species. The incubation of dPB with RLMs and HLMs resulted in eight (B1–B8) and nine (B1–B9) metabolites, respectively, while both RLMs and HLMs converted dPE into 13 metabolites (E1–13). B1 and E1 were unambiguously identified as (−)-cis-khellactone. The formations of all the metabolites were NADPH-dependent. Oxidation and hydrolysis were demonstrated to be two predominant metabolic pathways of dPB and dPE. Oxidation initiated at either the C-3′ or C-4′ substituent, while hydrolysis only started from the C-3′ substituent. Fragmentation of all metabolites followed similar pathways to those of the parent pyranocoumarins. The information on metabolic properties of dPB and dPE and the mass fragmentation profiles of their metabolites obtained in the present study will aid in characterization of metabolic profiles of other angular-type pyranocoumarins and further investigation of in vivo fates of these pyranocoumarins and the herb.