Synthesis and modulation of cytokine production by two new adamantane substituted acyclic desmuramyldipeptide analogs

Pharmazie. 2001 Jul;56(7):523-6.

Abstract

Two new adamantyl-desmuramyldipeptides LK 415 and LK 517 with 1-adamantylcarboxamido moiety as a replacement for muramyldipeptide's N-acetylglucosamine fragment were synthesized. Their efficacy to modulate the production of cytokines was measured in vitro in ionomycin and phorbol-12-myristate-13-acetate (PMA) activated cultures of human peripheral blood mononuclear cells (PBMC), co-incubated with the substances tested. The results were compared with the activity of muramyldipeptide (MDP). All three substances are strong up-regulators of IL-12 synthesis and hence of the IFN gamma synthesis as well. While MDP and LK 415 are relatively ineffective in modulation of IL-2, IL-4 and IL-10 production in vitro, the synthesis of all three cytokines is considerably up-regulated when peripheral blood mononuclear cells are co-incubated with LK 517. It seems likely that the introduction of the diethyl phosphonate moiety into LK 517 is of great importance for the augmented T-cell cytokine production.

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives
  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology*
  • Adamantane / analogs & derivatives
  • Adamantane / chemical synthesis*
  • Adamantane / pharmacology*
  • Adjuvants, Immunologic / chemical synthesis*
  • Adjuvants, Immunologic / pharmacology*
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Dipeptides / chemical synthesis*
  • Dipeptides / pharmacology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukins / biosynthesis
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Dipeptides
  • Interleukins
  • LK 415
  • LK 517
  • Tumor Necrosis Factor-alpha
  • Acetylmuramyl-Alanyl-Isoglutamine
  • Interferon-gamma
  • Adamantane