title: Chemo-enzymatic synthesis of ester-linked docetaxel-monosaccharide conjugates as water-soluble prodrugs.
abstract: Three new docetaxel prodrugs, i.e., 7-propionyldocetaxel 3''-O-β-D-glycopyranosides, which contain ester-linked monosaccharides, were synthesized by a chemo-enzymatic procedure involving enzymatic transglycosylations with lactase, β-galactosidase, or β-xylosidase. The water-solubility of 7-propionyldocetaxel 3''-O-β-D-glucopyranoside was 52-fold higher than that of docetaxel. 7-Propionyldocetaxel 3''-O-β-D-glucopyranoside and 7-propionyldocetaxel 3''-O-β-D-xylopyranoside were effectively hydrolyzed by the relevant enzyme(s) of human cancer cells to release docetaxel, whereas 7-propionyldocetaxel 3''-O-β-D-galactopyranoside was relatively resistant under similar conditions. 7-Propionyldocetaxel 3''-O-β-D-glucopyranoside and 7-propionyldocetaxel 3''-O-β-D-xylopyranoside showed in vitro cytotoxic activity against human cancer cells, whereas 7-propionyldocetaxel 3''-O-β-D-galactopyranoside exerted low cytotoxicity.
authors.affiliation: Department of Chemistry, Faculty of Medicine, Oita University, 1-1 Hasama-machi, Oita 879-5593, Japan. shimoda@med.oita-u.ac.jp
authors.forename: Kei
authors.initials: K
authors.lastname: Shimoda
authors.forename: Naoji
authors.initials: N
authors.lastname: Kubota
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D000077143:Docetaxel; D004952:Esters / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism*; D006001:Glycoconjugates / Q000737:chemistry* / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D006868:Hydrolysis; D043322:Lactase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009005:Monosaccharides / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology; D014867:Water; D014995:Xylosidases / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D005656:Fungal Proteins; D006001:Glycoconjugates; D009005:Monosaccharides; D011355:Prodrugs; D043823:Taxoids; D014867:Water; D000077143:Docetaxel; D014995:Xylosidases; D043322:Lactase; D001616:beta-Galactosidase; C026579:exo-1,4-beta-D-xylosidase