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Molecules 2011, 16(8), 6769-6777; doi:10.3390/molecules16086769
Article

Chemo-Enzymatic Synthesis of Ester-Linked Docetaxel-Monosaccharide Conjugates as Water-Soluble Prodrugs

*  and
Received: 24 June 2011; in revised form: 28 July 2011 / Accepted: 3 August 2011 / Published: 9 August 2011
(This article belongs to the Special Issue Enzyme-Catalyzed Reactions)
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Abstract: Three new docetaxel prodrugs, i.e., 7-propionyldocetaxel 3''-O-b-D-glycopyranosides, which contain ester-linked monosaccharides, were synthesized by a chemo-enzymatic procedure involving enzymatic transglycosylations with lactase, b-galactosidase, or b-xylosidase. The water-solubility of 7-propionyldocetaxel 3''-O-b-D-glucopyranoside was 52-fold higher than that of docetaxel. 7-Propionyldocetaxel 3''-O-b-D-glucopyranoside and 7-propionyldocetaxel 3''-O-b-D-xylopyranoside were effectively hydrolyzed by the relevant enzyme(s) of human cancer cells to release docetaxel, whereas 7-propionyldocetaxel 3''-O-b-D-galactopyranoside was relatively resistant under similar conditions. 7-Propionyldocetaxel 3''-O-b-D-glucopyranoside and 7-propionyldocetaxel 3''-O-b-D-xylopyranoside showed in vitro cytotoxic activity against human cancer cells, whereas 7-propionyldocetaxel 3''-O-b-D-galactopyranoside exerted low cytotoxicity.
Keywords: docetaxel; chemo-enzymatic synthesis; glycoside; ester-linker; prodrug; cytotoxicity docetaxel; chemo-enzymatic synthesis; glycoside; ester-linker; prodrug; cytotoxicity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Shimoda, K.; Kubota, N. Chemo-Enzymatic Synthesis of Ester-Linked Docetaxel-Monosaccharide Conjugates as Water-Soluble Prodrugs. Molecules 2011, 16, 6769-6777.

AMA Style

Shimoda K, Kubota N. Chemo-Enzymatic Synthesis of Ester-Linked Docetaxel-Monosaccharide Conjugates as Water-Soluble Prodrugs. Molecules. 2011; 16(8):6769-6777.

Chicago/Turabian Style

Shimoda, Kei; Kubota, Naoji. 2011. "Chemo-Enzymatic Synthesis of Ester-Linked Docetaxel-Monosaccharide Conjugates as Water-Soluble Prodrugs." Molecules 16, no. 8: 6769-6777.


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