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. An inverse relationship was found between stimulatory activity and dose of alpha- and beta-cyclododecyl glycosides of muramyl dipeptide during sepsis caused by Staphylococcus aureus.
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.
Beta-cyclohexylmethyl-, beta-cyclohexylethyl-, and beta-4-tert-butyl-cyclohexyl glycosides of muramyl dipeptide were shown to increase the resistance of mice to intraperitoneal infection with cultures of Staphylococcus aureus and Escherichia coli. These compounds increased the production of cytokines by mononuclear cells from healthy donors. Beta-cyclohexylethyl glycoside of muramyl dipeptide was more potent than muramyl dipeptide and other derivatives in increasing in vivo antibacterial resistance and in vitro production of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma;. This glycopeptide had a strong stimulatory effect on the production of interleukin-4 and tended to stimulate the synthesis of interferon-alpha. Beta-cyclohexylmethyl glycoside of muramyl dipeptide was most potent in stimulating the production of interleukin-4. Biological activity of beta-4-tert-butyl-cyclohexyl glycoside of muramyl dipeptide was lower than that of other glycosides of muramyl dipeptide.
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