One-Pot Enzymatic Synthesis and Biological Evaluation of Ganglioside GM3 Derivatives as Potential Cancer Immunotherapeutics

J Med Chem. 2022 Feb 10;65(3):1883-1897. doi: 10.1021/acs.jmedchem.1c01301. Epub 2022 Jan 24.


Cancer is a leading cause of death worldwide. Recent research studies have revealed that GM3 derivatives have considerable promise as potential therapeutic agents for cancer. To discover novel GM3 derivatives as potential antitumor agents, a one-pot enzymatic synthesis was established, yielding 14 GM3 derivatives in high total yields (22-41%). Subsequently, the inhibitory activities of GM3 derivatives were assessed by wound-healing assays and Transwell assays and tumor-bearing animal models. Among all the GM3 derivatives, N-12 showed excellent migration and invasion inhibitory effects in cells and marked antitumor activity in C57BL/6 mice. The subsequent analysis of cancer tissues and serum samples revealed that N-12 induces tumor inhibition, which was closely related to immune response. Taken together, N-12 can be further developed as an effective therapeutic for the treatment of cancer. An RNA-sequencing (RNA-seq) analysis was then performed and indicated that the antitumor mechanism of N-12 involved focal adhesion and ECM-receptor interaction signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cytokines / metabolism
  • G(M3) Ganglioside / analogs & derivatives*
  • G(M3) Ganglioside / chemical synthesis
  • G(M3) Ganglioside / pharmacokinetics
  • G(M3) Ganglioside / therapeutic use*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunity / drug effects
  • Immunotherapy
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Necrosis / chemically induced
  • Neoplasms / drug therapy*
  • Signal Transduction / drug effects


  • Antineoplastic Agents
  • Cytokines
  • G(M3) Ganglioside