Biological activity of anomeric pairs of lipophilic glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine.

We studied the capacity of anomeric pairs of alpha- and beta-dodecyl, alpha- and beta-(1-pentylhexyl), and alpha- and beta-cyclododecyl glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) to stimulate the nonspecific resistance of mice to intraperitoneal infection of Staphylococcus aureus and Escherichia coli cultures. Intraperitoneal pretreatment with the test substances in a wide dose range increased survival of infected animals. No differences were found between the biological effects of alpha- and beta-dodecyl and alpha- and beta-(1-pentylhexyl) glycosides of muramyl dipeptide.

[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.

Stimulation of mouse resistance to bacterial infection with muramyl dipeptide glycoside.

We studied the capacity of 9 new muramyl dipeptide glycosides to stimulate mouse resistance to experimental sepsis induced by intraperitoneal injection of salmonella typhimurium culture. Preventive intraperitoneal injections of muramyl dipeptide beta-glycosides better improved survival of infected animals compared to the original (unmodified) muramyl dipeptide and muramyl dipeptide alpha-glycosides. The most effective drug muramyl dipeptide beta-heptylglycoside injected during sepsis development also reduced animal mortality, decreased bacterial contamination of the viscera, and increased phagocytic activity of peritoneal macrophages in infected animals.

Effect of configuration of muramyl dipeptide glycoside bond and structure of glycoside aglycon on their capacity to stimulate production of interleukin-1 and tumor necrosis factor by macrophages.

Effects of 11 original glycoside derivatives of muramyl dipeptide on the production of interleukin-1 and tumor necrosis factor by mouse peritoneal macrophages were studied. The relationship between macrophage activation evaluated by induction of these cytokines and configuration of glycoside bond and aglycon structure of MDP was revealed.