191536-23-9

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• 156127-34-3 taxuyunnanin C 

Relevant academic research and scientific papers

Synthesis and biological evaluation of taxinine analogues as orally active multidrug resistance reversal agents in cancer

Three novel taxinine analogues were prepared and tested for their activity as multidrug resistance (MDR) reversal agents in comparison with verapamil. In vitro testing demonstrated that compounds 8-10 possess MDR-reversal activity in the KB/V cell line. In accumulation assay, the intracellular rhodamine123 concentration increased significantly after treatment with compound 9, higher than that of verapamil in KB/V cell line. In vivo studies with VCR-resistant KB/V tumor xenografts showed that 9 in combination with VCR significantly inhibited tumor growth. Treatment with VCR or 9 alone did not result in growth inhibition. Three novel taxinine analogues were prepared and tested for their activity as multidrug resistance (MDR) reversal agents in comparison with verapamil. In vitro testing demonstrated that compounds 8-10 possess MDR-reversal activity in the KB/V cell line. Half-hour after treatment with 5, 10, and 20 μmol/L compound 9, the intracellular rhodamine123 concentration increased 2.3, 2.9, and 3.2-fold, respectively, higher than 1.88-fold of 10 μmol/L verapamil in KB/V cell line. In vivo studies with VCR-resistant KB/V tumor xenografts showed that compound 9 in combination with VCR significantly inhibited tumor growth. Treatment with VCR or 9 alone did not result in growth inhibition. These results reveal that three taxinine analogues are good modifiers of MDR in tumor cells.

Synthesis and structure-activity relationships of sinenxan A derivatives as multidrug resistance reversal agents

Two types of sinenxan A derivatives with different side chains at C-5 were synthesized and evaluated for their in vitro multidrug resistant reversal activities. Several derivatives exhibited better activities than the positive control verapamil. The structure-activity relationships of these derivatives suggested that a carbonyl group at C-13 and the length of side chain at C-5 are important for the activity.

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.