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

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.