- Enantioseparation and absolute configuration determination of angular-type pyranocoumarins from Peucedani radix using enzymatic hydrolysis and chiral HPLC-MS/MS analysis
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Angular-type pyranocoumarins from Peucedani Radix (Chinese name: Qian-hu) have exhibited potential for use on treatment of cancer and pulmonary hypertension. Due to the existence of C-3′ and C-4′ chiral centers, compounds belonging to this chemical type commonly exist in enantiomers and/or diastereoisomers, which may elicit distinct activities during their interactions with the human body. In the present study, a new method, which combines enzymatic hydrolysis with chiral LC-MS/MS analysis, has been developed to determine the absolute configurations of these angular-type pyranocoumarins. Pyranocoumarins isolated from Qian-hu, their enantiomers, or metabolites were individually incubated with rat liver microsomes. As the common end product from enzymatic hydrolysis of all tested pyranocoumarins, cis-khellactone was collected and its absolute configuration was determined by comparison with (+)-cis-khellactone and (-)-cis-khellactone using chiral LC-MS/MS. The absolute configurations of all tested parent pyranocoumarins were determined by combination of LC-MS/MS, NMR and polarimetric analysis. The results revealed that the metabolite cis-khellactone retained the same absolute configurations of the stereogenic carbons as the respective parent compound. This method was proven to be rapid and sensitive and also has advantages in discriminating single enantiomers and mixtures of optical isomers with different ratios.
- Song, Yue-Lin,Zhang, Qing-Wen,Li, Ya-Ping,Yan, Ru,Wang, Yi-Tao
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experimental part
p. 4236 - 4251
(2012/07/27)
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- The antagonistic effects of khellactones on platelet-activating factor, histamine, and leukotriene D4
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Khellactones of Peucedanum praeruptorum Duun., including praeruptorins A (= Pd-Ia, 2) and B (= Pd-II, 11), had an antagonistic effect specifically on platelet aggregation induced by platelet activating factor (PAF) among various aggregating agents examined, and represent a new class of PAF antagonists. We examined the effects of twenty compounds on PAF-induced platelet aggregation and on histamine- and leukotriene D4 (LTD4)-induced contractions in isolated guinea pig ileum. Compounds 2, (±)-cis-3',4'-diacetylkhellactone (3), (±)-cis-4'-acetyl-3'-crotonoylkhellactone (5), (±)-cis-4'-acetyl-3'-tetrolylkhellactone (6), (±)-cis-4'-acetyl-3'-tigloylkhellactone (7), (±)-cis-4'-acetyl-3'-(2''-methylbutyryl)khellactone (8), (±)-cis-3',4'-ditigloylkhellactone (10), and 11 all strongly inhibited PAF-induced platelet aggregation. (±)-cis-4'-Acetyl-3'-(2''-methyl-2''-dodecenoyl)khellactone (9), (±)-cis-4'-ethyl-3'-tigloylkhellactone (13), (±)-cis-4'-ethyl-3'-[N-(2''-triethylammonio)ethylcarbamoyl]khellacton e iodide (16), (±)-trans-3',4'-diacetylkhellactone (18), (±)-trans-4'-acetyl-3'-crotonoylkhellactone (19), (±)-trans-4'acetyl-3'-valerylkhellactone (20), (±)-trans-4'-acetyl-3'-isovalerylkhellactone (21), and (±)-trans-4'-acetyl-3'-tigloylkhellactone (22) were weakly inhibitory. Most of the compounds exhibited noncompetitive antagonist actions on histamine- and LTD4-induced contractions. The potencies of the antagonistic effects on histamine action were in the order 7 = 22 ≥ 2 = 8 = 10 > 6 = 11 = 13 ≥ 5 > 19 = 9 and those on LTD4 action were in the order 6 = 22 = 2 > 10 = 8 > 7 = 9 = 11 ≥ 13. Thus, compounds with potent PAF-antagonistic activities have the following features: cis isomers of khellactone at the C-3' and C-4' positions are more favorable than trans isomers, and the acyl moiety at the C-3' position of khellactone must be of an appropriate molecular size. In the case of histamine- and LTD4-antagonistic activities, both isomers show similar effects and acyl moieties of appropriate size are required at the C-3' and C-4' positions. These results are of interest in regard to the medicinal uses of Peucedanum species as a herbal drug.
- Aida,Kasama,Takeuchi,Tobinaga
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p. 859 - 867
(2007/10/02)
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