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• 156127-34-3 taxuyunnanin C 

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Relevant academic research and scientific papers

Synthesis and structure-activity relationships of taxuyunnanine C derivatives as multidrug resistance modulator in MDR cancer cells

A series of new generation taxoids bearing a bulky group on different positions such as C-2, C-5, C-7, C-9, C-10 or C-14 were obtained by chemical modifications and biotransformation of taxuyunnanine C (1) and its analogs, 4, 5, and 10. Compounds 3, 5, 6, 8, and 9a showed significant activity toward calcein accumulation in MDR 2780AD cells. The most effective compound 9a with a cinnamoyloxy group at C-14 and a hydroxyl group at C-10 was actually efficient for the cellular accumulation of the anticancer agent, vincristine, in MDR 2780AD cells. The enhancing effects of 6 and 9a for taxol, adriamycin, and vincristine were at the same levels as those of verapamil toward MDR 2780AD cells. Thus, compounds 6 and 9a can modulate the multidrug resistance of cancer cells. The cytotoxicity (IC50) of the compounds was examined against human normal cell line, WI-38, and cancer model cell lines, VA-13 and HepG2. Since compounds 6 and 8 had no cytotoxicity, they were expected to be lead compounds of MDR cancer reversal agents. On the contrary, compounds 3, 5, and 9a showed cell growth inhibitory activity toward VA-13 and/or HepG2 as well as accumulation activity of calcein and/or vincristine in MDR 2780AD and they were expected to be lead compounds of new-type anticancer agents.

Substrate specificity for the hydroxylation of polyoxygenated 4(20),11-taxadienes by Ginkgo cell suspension cultures

Three C-14 oxygenated taxanes isolated from callus cultures of Taxus spp., 2α,5α,10β,14β-tetra-acetoxy-4(20),11-taxadiene 3, 2α,5α,10β-triacetoxy-14β-propionyloxy-4(20),11- taxadiene 4, 2α,5α,10β-triacetoxy-14β-(2-methylbutyryl)-oxy-4(20), 11-taxadiene 5, and three deacetylated derivatives of 3, 10β-hydroxy-2α,5α,14β-triacetoxy-4(20),11-taxadiene 6, 14β-hydroxy-2α,5α,10β-triacetoxy-4(20),11-taxadiene 7, 10β,14β-dihydroxy-2α,5α-diacetoxy-4(20),11-taxadiene 8, could all be regio- and stereo-selectively hydroxylated at the 9α-position by Ginkgo cell suspension cultures to yield a series of new 9α,14β-dihydroxylated taxoids. The effects of functional groups, especially at C-14 of the substrates, on the biotransformation were also investigated. The results revealed that substrates with an acetoxyl group at C-14 could be more efficiently 9α-hydroxylated than those with a longer ester chain or a hydroxyl group at C-14. An acetoxyl or hydroxyl group at C-10 had no effect on the conversion rates of the substrates, but substrates with the hydroxyl group (compared with the acetoxyl analogues) could be converted into 9α-hydroxylated products more easily.

Purification and characterization of acetyl coenzyme A: 10- hydroxytaxane O-acetyltransferase from cell suspension cultures of Taxus chinensis

An O-acetyltransferase that catalyzes the regiospecific acetylation of a range of taxanes possessing an unsubstituted 10-hydroxyl group was detected and purified to apparent electrophoretic homogeneity from a cytosolic fraction of Taxus chinensis cell cultures. The purification involved negative calcium phosphate adsorption, sephadex desalting, DEAE, AcA44 chromatography, HighQ, CHT II, HiTrap Blue, Phenylsepharose and Mimetic Green purification steps. The purified acetyltransferase was found to be a monomeric protein of 71 ± 1.5 kDa that is highly regio- and stereospecific towards the 10β- hydroxyl group of the taxane molecule and is also active towards 10- desacetylbaccatine III. The acetyltransferase reaction had a pH optimum of 9.0 with halfmaximal activities at pH 6.8 and 10.8, respectively. The temperature optimum was at 35°C and the isoelectric point at 5.6. The apparent K(m) values for 10-desacetyltaxuyunnanine C and acetyl CoA were 23 and 61 μM, respectively. The turnover rate for the enzyme using both substrates was 0.2 mol mol-1 of enzyme. The kinetic optimum was determined to be K(cat)/K(m) = 8.7 s-1 L M-1.