The phase II metabolite of acetaminophen in filamentous fungi and actinomycetes separated from soil was investigated. Fifty-four filamentous fungi and twenty-seven actinomycetes were screened to transform acetaminophen. The metabolites of acetaminophen were assayed using liquid chromatography-tandem mass spectrometry. The only metabolite was subject to enzymatic hydrolysis to confirm its structure. Acetaminophen was converted into glucoside conjugate, by filamentous fungi JX1-60, LN17-2, LN20-1 and the yield of the conjugate was 60.01%, 44.27%, 100%, respectively, and no phase I metabolites were detected. Glucoside conjugation of acetaminophen in filamentous fungi differs from the phase II metabolism of glucuronidation in humans. The fungus LN20-1 could be a suitable model to synthesize glucoside conjugate of acetaminophen.

The capability of Cunninghamella blakesleeana AS 3.153 to transform CYP2D6 probe drug dextromethorphan was investigated. Metabolites produced by strain AS 3.153 were detected by liquid chromatography-tandem mass spectrometry (LC-MS n ) and the metabolite dextrorphan was identified by reference to confirm its structure. The yield of dextrorphan produced by C. blakesleeana AS 3.153 was over 90%. Quinidine, a CYP2D6 selective inhibitor, was applied to investigate its effect on biotransformation. The concentration of quinidine was 4-folds higher than that of dextromethorphan and the yield of dextrorphan was reduced by 84%, which proved there was drug metabolism enzyme similar to CYP2D6 in C. blakesleeana AS 3.153. It is concluded that C. blakesleeana AS 3.153 can be used as the suitable model strain in vitro to mimic human CYP2D6 metabolism.

A new bufadienolide named 16beta-acetoxy-bufarenogin (1), together with six known bufadienolides, namely, 11alpha,12beta-dihydroxy-bufalin (2), bufotalin (3), hellebrigenin (4), desacetylbufotalin (5), gamabufotalin (6), and resibufagin (7) were isolated from Chan'Su. Of these, 2 was a new natural product. Their structures were elucidated by spectral methods. The cytotoxic activities in vitro of these compounds have been assayed against HeLa cell line. They all showed strong cytotoxic activities.

Cunninghamella elegans has been employed for the biotransformation of cinobufagin to afford 5 metabolites. The structures of the transformation products have been characterized as 12a -hydroxybufagin, 11a -hydroxybufagin, 12b-hydroxy-desacetylcinobufagin, 3-oxo12a -hydroxybufagin and 12b -hydroxybufagin. Products 12a -hydroxybufagin and 11a -hydroxybufagin are new compounds. In vitro both the biotransformation products and cinobufagin all showed cytotoxic activities against HeLa cells.

Terpenes U 0200Two New Sesquiterpene Lactones with the Sulfonic Acid Group from Saussurea lappa. -Two new sesquiterpene lactones with the unusual sulfonic acid group, 13-sulfo-dihydrosantamarine (I) and 13-sulfo-dihydroreynosin (II), are isolated from the roots of the title plant. Their structures, including the absolute configurations, are elucidated by spectroscopic methods. -(YIN, H.-Q.; FU, H.-W.; HUA, H.-M.; QI, X.-L.; LI, W.; SHA, Y.; PEI*, Y.-H.; Chem. Pharm. Bull. 53 (2005) 7, 841-842; Coll. Tradit. Chin. Med., Shenyang Pharm. Univ., Shenyang 110016, Peop. Rep. China; Eng.) -H. Haber 52-156