78432-77-6Relevant articles and documents
Formulation development and antitumor activity of a filter-sterilizable emulsion of paclitaxel
Constantinides, Panayiotis P.,Lambert, Karel J.,Tustian, Alex K.,Schneider, Brian,Lalji, Salima,Ma, Wenwen,Wentzel, Bryan,Kessler, Dean,Worah, Dilip,Quay, Steven C.
, p. 175 - 182 (2000)
Purpose. Paclitaxel is currently administered i.v. as a slow infusion of a solution of the drug in an ethanol:surfactant:saline admixture. However, poor solubilization and toxicity are associated with this drug therapy. Alternative drug delivery systems, including parenteral emulsions, are under development in recent years to reduce drug toxicity, improve efficacy and eliminate premedication. Methods. Paclitaxel emulsions were prepared by high- shear homogenization. The particle size of the emulsions was measured by dynamic light scattering. Drug concentration was quantified by HPLC and in vitro drug release was monitored by membrane dialysis. The physical stability of emulsions was monitored by particle size changes in both the mean droplet diameter and 99% cumulative distribution. Paclitaxel potency and changes in the concentration of known degradants were used as chemical stability indicators. Single dose acute toxicity studies were conducted in healthy mice and efficacy studies in B 16 melanoma tumor-bearing mice. Results. QW8184, a physically and chemically stable sub-micron oil-in-water (o/w) emulsion of paclitaxel, can be prepared at high drug loading (8-10 mg/mL) having a mean droplet diameter of a 3-fold increase in the maximum-tolerated-dose (MTD) over the current marketed drug formulation. Using the B16 mouse melanoma model, a significant improvement in drug efficacy was observed with QW8184 over Taxol. Conclusions. QW8184, a stable sub-micron o/w emulsion of paclitaxel has been developed that can be filter-sterilized and administered i.v. as a bolus dose. When compared to Taxol, this emulsion exhibited reduced toxicity and improved efficacy most likely due to the composition and dependent physicochemical characteristics of the emulsion.
Cloning and characterization of the β-xylosidase from Dictyoglomus turgidum for high efficient biotransformation of 10-deacetyl-7-xylosltaxol
Li, Qi,Jiang, Yujie,Tong, Xinyi,Pei, Jianjun,Xiao, Wei,Wang, Zhenzhong,Zhao, Linguo
, (2019/11/11)
With the aim of finding an extracellular biocatalyst that can efficiently remove the C-7 xylose group from 10-deacetyl-7-xylosltaxol, a Dictyoglomus turgidum β-xylosidase was cloned and expressed in Escherichia coli BL21 (DE3). The molecular mass of purified Dt-Xyl3 was approximately 84 kDa. The recombinant Dt-Xyl3 was most active at pH 5.0 and 75 °C, retaining 88% activity at 65 °C for 1 h, and displaying excellent stability over pH 4.0–7.5 for 24 h. In terms of kinetic parameters, the Km and Vmax values for pNPX were 0.8316 mM and 5.0178 μmol/mL·min, respectively. Moreover, Dt-Xyl3 was activated by Mn2+ and Ba2+ and inhibited by Cu2+, Ni+ and Al3+. In particular, it displayed high tolerance to salts with 60.8% activity in 20% (w/v) NaCl. Ethanol and methanol at 5–15% showed little effect on the enzymatic activity. Dt-Xyl3 demonstrated multifunctional activities followed by pNPX, pNPAraf and pNPG and had a high selectivity for cleaving the outer xylose moieties of 10-deacetyl-7-xylosltaxol with Kcat/Km 110.87 s?1/mM, which produced 10-deacetyl-taxol to semi-synthesize paclitaxel. Under the optimized conditions (60 °C, pH 4.5, enzyme dosage of 0.5 U/mL), 1 g of 10-deacetyl-7-xylosltaxol was transformed to its corresponding aglycone 10-deacetyl-taxol within 30 min, with a molar conversion of 98%. This is the first report that Dictyoglomus turgidum can produce extracellular GH3 β-xylosidase with highly specific activity for 10-deacetyl-7-xylosltaxol biotransformation, thus leading to the application of β-xylosidase Dt-Xyl3 as a biocatalyst in biopharmaceutics.
Glycosyl hydrolase with beta-xylosidase and beta-glucosidase activities and uses thereof
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Paragraph 18, (2015/12/26)
A novel glycosyl hydrolase with activities of beta-xylosidase and beta-glucosidase is provided. Said glycosyl hydrolase can convert 7-xylosyltaxane compounds to 7-hydroxyltaxane compounds.
Microbial hydrolysis of 7-xylosyl-10-deacetyltaxol to 10-deacetyltaxol
Wang, Kang,Wang, Tingting,Li, Jianhua,Zou, Jianhua,Chen, Yongqin,Dai, Jungui
experimental part, p. 250 - 255 (2011/10/12)
Enterobacter sp. CGMCC 2487, a bacterial strain isolated from the soil around a Taxus cuspidata Sieb. et Zucc. plant, was able to remove the xylosyl group from 7-xylosyltaxanes. The xylosidase of this strain was an inducible enzyme. In the bioconversion of 7-xylosyl-10-deacetyltaxol (7-XDT) to 10-deacetyltaxol (10-DT), for the purpose of enhancing the conversion efficiency, the effects of NH4+, oat xylan, temperature, pH value, cell density and substrate concentration on the bioconversion have been systematically investigated. 3.0 mM NH4+, 0.6% oat xylan in the media could enhance the yield of 10-DT; the optimum biocatalytic temperature was 26 °C and optimum pH value was 6.0. The highest conversion rate and yield of 10-DT from 7-XDT reached 92% and 764 mg/L, respectively. In addition, the biocatalytic capacity of the cell cultures remained 66.1% after continuous three batches. These results indicate that converting 7-XDT to 10-DT, a useful intermediate for the semisynthesis of paclitaxel or other taxane-based anticancer drugs by a novel bacterial strain, Enterobacter sp. CGMCC 2487, would be an alternative for the practical application in the future.
METHOD FOR THE PREPARATION OF SYNTHESIZED TAXANOIDS
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Page/Page column 5, (2010/02/17)
The present invention relates to a process for the preparation of synthetic taxanes, which protects C(7)-OH with lanthanon compounds. Its advantages are simple process and firm & reliable binding. Moreover, no C(7)-acylated taxanes are produced in the subsequent steps, and hydrolysis of C(2')-ester groups in acylated products becomes readily controllable. In the process for the preparation of synthetic taxanes, tetrahydrofuran is used in the present invention as a medium for acylation, which not only achieves the same effects as pyridine, but also avoids odor, so as to solve the problem regarding the extremely high requirements for the place of production. The present invention can be used for the preparation of not only semi-synthetic taxane using natural taxanes as raw material, but also full-synthetic taxane.
Biological degradation of taxol by action of cultured cells on 7-acetyltaxol-2″-yl glucoside
Shimoda, Kei,Mikuni, Katsuhiko,Nakajima, Kiyoshi,Hamada, Hatsuyuki,Hamada, Hiroki
, p. 362 - 363 (2008/09/20)
Biodegradation pathways of taxol in cultured cells of Synechocystis sp. PCC 6803, Synechococcus sp. PCC 7942, Marchantia polymorpha, Nicotiana tabacum, and Glycine max were investigated using a water-soluble taxol derivative, 7-ace-tyltaxol-2″-yl glucoside, as the substrate. Although cyanobacteria, Synechocystis sp. PCC 6803 and Synechococcus sp. PCC 7942, and a lower plant, M. polymorpha, catalyzed the epimerization at 7-position of taxol skeleton, no epimerization occurred with higher plants, N. tabacum and G. max. On the other hand, Synechocystis sp. PCC 6803, Synechococcus sp. PCC 7942, M. polymorpha, and N. tabacum catalyzed hydrolysis at 13-position of taxol to give baccatin III and 10-deacetyl baccatin III. Both cyanobacteria cells also deacetylated 7-epi-baccatin III at its 10-position. M. polymorpha and G. max deacetylated at 10-position of taxol. Copyright
Process for the Preparation of Synthetic Taxanes
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Page/Page column 3, (2008/12/09)
The present invention relates to a process for the preparation of synthetic taxanes, which protects C(7)-OH with lanthanon compounds. Its advantages are simple process and firm & reliable binding. Moreover, no C(7)-acylated taxanes are produced in the subsequent steps, and hydrolysis of C(2′)-ester groups in acylated products becomes readily controllable. In the process for the preparation of synthetic taxanes, tetrahydrofuran is used in the present invention as a medium for acylation, which not only achieves the same effects as pyridine, but also avoids odor, so as to solve the problem regarding the extremely high requirements for the place of production. The present invention can be used for the preparation of not only semi-synthetic taxane using natural taxanes as raw material, but also full-synthetic taxane.
METHOD FOR THE PRODUCTION OF TAXOL AND/OR TAXANES FROM CULTURES OF HAZEL CELLS
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, (2008/06/13)
Method for the production of taxol and/or taxanes, comprising the steps of: a) inducing the formation of callus from a plant tissue explant, through in vitro culturing in a suitable nutritient medium, b) cultivating the callus in a liquid medium to obtain a cell suspension culture capable of producing taxol and/or taxanes, c) recovering the taxol and/or the taxanes from the cells and/or from the culture medium of the cell suspension obtained from the callus in which the tissue explant is obtained from a plant of the genus Corylus, in particular Corylus avellana.
Trifluoroacetic acid-mediated cleavage of a triethylsilyl protecting group: Application in the final step of the semisynthetic route to paclitaxel (Taxol)
Singh, Ambarish K.,Weaver, Raymond E.,Powers, Gerald L.,Rosso, Victor W.,Wei, Chenkou,Lust, David A.,Kotnis, Atul S.,Comezoglu, F. Taha,Liu, Mark,Bembenek, Kenneth S.,Phan, Bich D.,Vanyo, Dale J.,Davies, Merrill L.,Mathew, Rachel,Palaniswamy, Venkatapuram A.,Li, Wen-Sen,Gadamsetti, Kumar,Spagnuolo, Ciro J.,Winter, William J.
, p. 25 - 27 (2013/09/05)
The final step of the semisynthetic route to paclitaxel involves cleavage of the triethylsilyl (TES) protecting group from the C-7 hydroxyl group. Paclitaxel is an extremely complex molecule, and standard deprotection conditions led to formation of several impurities. Trifluoroacetic acid in aqueous acetic acid was found to be very effective in the cleavage of the TES group without compromising the quality of the product.
Mechanistic considerations pertaining to the solvolysis of paclitaxel analogs bearing ester groups at the C2′ position
Klis, Wieslaw A.,Sarver, Jeffrey G.,Erhardt, Paul W.
, p. 7747 - 7750 (2007/10/03)
Dilute solutions of paclitaxel-related derivatives having chloroacetyl esters in the C2′ position undergo ready methanolysis according to pseudo first-order kinetics while more concentrated solutions appear to be stabilized, possibly by the formation of h
