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Abstract

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 Cycloalkyl Glycosides of Muramyl Dipeptide on Antibacterial Resistance of Mice and Cytokine Production by Human Mononuclear Cells

“…O. V. Kalyuzhin N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide, MDP) was extensively studied by immunoph armacologists for more than 35 years. Chemical modifi cation of this molecule resulted in the deve lopment of some immunotropic substances and large group of pharmacological drugs to increase the antiinfectious and antitumor immunity [2,3,8]. The molecular mechanisms for action of MDP and its derivatives include an agonistic relationship between pattern-re cognizing receptors NOD-2 [9].…”

“…We previously attempted to attach a cyclic structure to the glycoside site of MDP. Biological activity of glycopeptide (β-cyclohexyl glycoside of MDP and β-adamantyl glycoside of MDP) increased [5,6,7], remained unchanged, or even decreased under these conditions (α-and β-cyclododecyl glycosides of MDP) [4].Here we evaluated the capacity of new cycloalkyl glycosides of MDP to increase the resistance of mice to infections with gram-positive and gram-negative bacteria and to stimulate the production of cytokines by human mononuclear cells. …”

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

“…No differences were found between the biological effects of α-and β-dodecyl and α-and β-(1-pentylhexyl) glycosides of muramyl dipeptide. An inverse relationship was found between stimulatory activity and dose of α-and β-cyclododecyl glycosides of muramyl dipeptide during sepsis caused by Staphylococcus aureus.In vitro and in vivo studies showed that hydrophilic and amphiphilic glycosides of N-acetylmuramyl-Lalanyl-D-isoglutamine (muramyl dipeptide, MDP) with β-glycoside bond surpass α-anomers and unmodified MDP by immunostimulatory activity [4][5][6][7][8][9]12]. The increase in lipophilicity of glycopeptides can be accompanied by significant changes in the mechanisms of their permeation through the plasmalemma of immunocompetent cells and interaction with surface and intracellular binding sites [4,11,12].…”

“…The increase in lipophilicity of glycopeptides can be accompanied by significant changes in the mechanisms of their permeation through the plasmalemma of immunocompetent cells and interaction with surface and intracellular binding sites [4,11,12].…”