The Effect of Deoxyfluorination and O-Acylation on the Cytotoxicity of N-Acetyl-D-Gluco- and D-Galactosamine Hemiacetals.

0542205 - ÚCHP 2022 RIV GB eng J - Journal Article
Hamala, Vojtěch - Červenková Šťastná, Lucie - Kurfiřt, Martin - Cuřínová, Petra - Balouch, M. - Hrstka, R. - Vońka, P. - Karban, Jindřich
The Effect of Deoxyfluorination and O-Acylation on the Cytotoxicity of N-Acetyl-D-Gluco- and D-Galactosamine Hemiacetals.
Organic & Biomolecular Chemistry. Roč. 19, č. 20 (2021), s. 4497-4506. ISSN 1477-0520. E-ISSN 1477-0539
R&D Projects: GA ČR(CZ) GA17-18203S; GA MŠMT(CZ) LTC20052
Grant - others:MEYS(XE) CA18103
Institutional support: RVO:67985858
Keywords : cytotoxicity * deoxyfluorination * breast cancer
OECD category: Organic chemistry
Impact factor: 3.890, year: 2021
Method of publishing: Open access with time embargo

Fully acetylated deoxyfluorinated hexosamine analogues and non-fluorinated 3,4,6-tri-O-acylated N-acetyl-hexosamine hemiacetals have previously been shown to display moderate anti-proliferative activity. We prepared a set of deoxyfluorinated GlcNAc and GalNAc hemiacetals that comprised both features: O-acylation at the non-anomeric positions with an acetyl, propionyl and butanoyl group, and deoxyfluorination at selected positions. Determination of the in vitro cytotoxicity towards the MDA-MB-231 breast cancer and HEK-293 cell lines showed that deoxyfluorination enhanced cytotoxicity in most analogues. Increasing the ester alkyl chain length had a variable effect on the cytotoxicity of fluoro analogues, which contrasted with non-fluorinated hemiacetals where butanoyl derivatives had always higher cytotoxicity than acetates. Reaction with 2-phenylethanethiol indicated that the recently described S-glyco-modification is an unlikely cause of cytotoxicity.
Permanent Link: http://hdl.handle.net/11104/0320364