title: Synthesis and preliminary biological assay of uridine glycoconjugate derivatives containing amide and/or 1,2,3-triazole linkers.
abstract: A series of UDP-sugar analogues was synthesized and their preliminary biological activity was evaluated. Glycoconjugates of uridine 1 and 2 were synthesized by condensation of uridine-5'-carboxylic acid and 1-amino sugars derivatives of d-glucose and d-galactose, glycoconjugates 3 and 4 were synthesized by azide-alkyne 1,3-dipolar cycloaddition (CuAAC) of 1-azido sugars and propargylamide derivatives of uridine while glycoconjugates 5 and 6 were synthesized by CuAAC of propargyl β-O-glycosides and 5'-azido uridine. Evaluation of inhibitory activity of compounds 1-6 against commercially available β-1,4-galactosyltransferase I (β4GalT) show that compound 5 inhibited the enzyme in µmolar range. Additionally, the antitumor activity of the obtained glycoconjugates 1-6 were tested using MTT assay.
authors.affiliation: Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland; Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland. Electronic address: gabriela.pastuch@polsl.pl.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pastuch-Gawolek
authors.affiliation: Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Plesniak
authors.affiliation: Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Komor
authors.affiliation: Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Byczek-Wyrostek
authors.affiliation: Department of Chemical Organic Technology and Petrochemistry, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland.
authors.forename: Karol
authors.initials: K
authors.lastname: Erfurt
authors.affiliation: Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland; Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland.
authors.forename: Wieslaw
authors.initials: W
authors.lastname: Szeja
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008892:Milk / Q000201:enzymology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*; D014529:Uridine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000577:Amides; D006001:Glycoconjugates; D014230:Triazoles; D005700:Galactosyltransferases; C119701:beta-1,4-galactosyltransferase I; D014529:Uridine
keywords: Click chemistry; Glycoconjugates; Glycosyltransferase inhibitors; Uridine derivatives