Specific methylation and epoxidation of sinenxan A by Mucor genevensis and the multi-drug resistant tumor reversal activities of the metabolites |
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Authors: | Lin Yang Runjiang Qu Jungui Dai Xiaoguang Chen |
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Institution: | aDepartment of Biosynthesis for the Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College (Key Laboratory of Bioactive Substances and Resources Utilization, Ministry of Education), 1 Xian Nong Tan Street, Beijing 100050, PR China bDepartment of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, PR China cCollege of Life and Environmental Sciences, The Central University for Nationalities, 27 South Zhongguancun Street, Beijing 100081, PR China |
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Abstract: | Mucor genevensis were used to bioconvert sinenxan A 2α,5α,10β,14β-tetraacetoxy-taxa-4(20),11-diene], a taxoid isolated from callus tissue cultures of Taxus spp., and 10 metabolites were obtained. On the basis of chemical and spectroscopic data analyses, their structures were determined as 10β-methoxy-2α,5α,14β-triacetoxy-taxa-4(20),11-diene (2), 10β-hydroxy-2α,5α,14β-triacetoxy-taxa-4(20),11-diene (3), 2α,5α,10β,14β-tetraacetoxy-4β,20-epoxy-taxa-11(12)-ene (4), 6α-hydroxy-2α,5α,10β,14β-tetraacetoxy-taxa-4(20),11-diene (5), 9α-hydroxy-2α,5α,10β,14β-tetraacetoxy-taxa-4(20),11-diene (6), 10β-hydroxy-2α,5α,14β-triacetoxy-4β,20-epoxy-taxa-11(12)-ene (7), 6α,10β-dihydroxy-2α,5α,14β-triacetoxy-taxa-4(20),11-diene (8), 6α-hydroxy-2α,5α,10β,14β-tetraacetoxy-4β,20-epoxy-taxa-11(12)-ene (9), and 9α,10β-dihydroxy-2α,5α,14β-triacetoxy-taxa-4(20),11-diene (10), and 9α,10β-O-(propane-2,2-diyl)-2α,5α,14β-triacetoxy-taxa-4(20),11-diene (11). Among them, metabolites 2, 4, and 9 were three new compounds. The three major metabolites 2, 3, and 4 along with 1 were pharmacologically evaluated for their multi-drug resistance (MDR) reversal activities towards taxol-resistant A549 tumor cells, and the results showed that 4 possessed about two-fold activity as verapamil, while 2, and 3 possessed lower activity than verapamil and 1. |
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Keywords: | Taxanes Biotransformation Mucor genevensis Tumor MDR reversal activity |
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