Dialkylmethyl β-glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine: Synthesis and protective antiinfection and cytotoxic activities

Autor: O. V. Kalyuzhin, M. V. Kiselevsky, E. L. Mulik, V. N. Tsikalova, A. E. Zemlyakov, V. V. Tsikalov, F. N. Kuzovlev, V. Ya. Chirva
Rok vydání: 2008
Předmět:
Zdroj: Russian Journal of Bioorganic Chemistry. 34:103-109
ISSN: 1573-9163
1068-1620
DOI: 10.1134/s1068162008010147
Popis: Symmetric secondary linear alcohols were proposed as aglycones for the synthesis of lipophilic glycosides of β-N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). Pentadecan-8-ol, nonadecan-10-ol, and tricosan-12-ol were glycosylated by the oxazoline method. Based on the corresponding glucosaminides, alkyl β-glycosides of 4,6-O-isopropylidene-N-acetylmuramic acid were synthesized and coupled with the dipeptide. Deprotection of isopropylidene groups by acidic hydrolysis and catalytic hydrogenolysis of benzyl esters resulted in the target muramyldipeptide glycosides. Nonadecan-10-yl and tricosan-12-yl β-MDPs at doses 2 μg/mice most effectively stimulated antibacterial resistance in mice against Staphylococcus aureus. In contrast to the previously synthesized undecan-6-yl β-MDP, pentadecan-8-yl, nonadecan-10-yl, and tricosan-12-yl β-MDPs demonstrated direct cytotoxicity toward tumor cells K-562 and blood mononuclear cells.
Databáze: OpenAIRE
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