ABSTRACT
1. Butyrolactone I (BL-I), one of the major secondary metabolites of fungus Aspergillus terreus, is a selective cdc2 kinase inhibitor. In the present study, the metabolism of BL-I in male Wistar rats was investigated by characterizing metabolites excreted into feces. 2. Following an oral dose of 40 mg/kg BL-I, 10 phase I metabolites were isolated from the feces of rats, and their structures were identified on the basis of a range of spectroscopic data and ICD analysis. These metabolites were fully characterized as butyrolactone VI (M1), aspernolide E (M2), 7''S-hydroxy-9''-ene-butyrolactone I (M3), 7''R-hydroxy-9''-ene-butyrolactone I (M4), 7â³S, 8â³R-dihydroxy-aspernolide E (M5), 7â³R, 8â³S-dihydroxy-aspernolide E (M6), 7â³R-acetyl-8â³S-hydroxy-aspernolide E (M7), 7â³S-acetyl-8â³R-hydroxy-aspernolide E (M8), 7â³R-methoxy-8â³S-hydroxy-aspernolide E (M9), butyrolactone V (M10), respectively. It is the first time to describe the metabolites of BL-I in vivo, and metabolites M3 to M9 are new compounds. 3. BL-I and metabolites M2 to M10 were evaluated for their antimicrobial activity and in vitro antiproliferative activities. Only M-3 and M-4 showed inhibitory effect against staphylococcus aureus both with MIC of 125 µg/ml. BL-I and metabolites M-4 and M-5 exhibited potent cancer cell growth inhibitory activities against HL-60 (human leukemia) cell lines with the IC50 values of 13.2, 28.8 and 35.7 µM, respectively. 4. On the basis of metabolites profile, a possible metabolism pathway for BL-I in rats has been proposed. This is the first systematic study on the phase I metabolites of BL-I.
Subject(s)
4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/isolation & purification , 4-Butyrolactone/metabolism , Animals , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/metabolism , Rats , Rats, Wistar , Staphylococcus aureusABSTRACT
OBJECTIVE: To isolate the chemical constituents of the peelings of Citrus grandis and determine their structure. METHOD: Column chromatography and PTLC were applied to isolating and purifying the chemical constituents, and 1H NMR and 13C NMR were used to elucidate their structure. RESULT: 4 compounds were isolated as meranzin hydrate(1), roseoside(2), 8-(3-beta-D-syl-2-hydrox-3-methylbutyl)-7-methoxycoumarin(3) and glucose(4). CONCLUSION: Compound 2 was isolated as a carotenoid from this genus for the first time.
