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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
Department of Chemistry, Faculty of Medicine, Oita University, 1-1 Hasama-machi, Oita 879-5593, Japan
* Author to whom correspondence should be addressed.
Received: 24 June 2011 / Revised: 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 (CC BY 3.0).
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Shimoda, K.; Kubota, N. Chemo-Enzymatic Synthesis of Ester-Linked Docetaxel-Monosaccharide Conjugates as Water-Soluble Prodrugs. Molecules 2011, 16, 6769-6777.

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