[Dialkylmethyl beta-glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine: synthesis and infection protective and cytotoxic activities].
Symmetric secondary linear alcohols were proposed as aglycones for the synthesis of lipophilic beta-glycosides of 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 beta-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 [beta]-MDPs at doses 2 microg/mice most effectively stimulated antibacterial resistance in mice against Staphylococcus aureus. In contrast to the previously synthesized undecan-6-yl beta-MDP, pentadecan-8-yl, nonadecan-10-yl, and tricosan-12-yl beta-MDPs demonstrated direct cytotoxicity toward tumor cells E-562 and blood mononuclear cells.
Zemliakov
A E
AE
Tsikalova
V N
VN
Tsikalov
V V
VV
Chirva
V Ia
VIa
Mulik
E L
EL
Kuzovlev
F N
FN
Kaliuzhin
O V
OV
Kiselevskií
M V
MV
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D051379:Mice; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus
D000900:Anti-Bacterial Agents; D003603:Cytotoxins; D006027:Glycosides; D000119:Acetylmuramyl-Alanyl-Isoglutamine