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

Abstract

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.