(356) Exploring the Role of Glycosylation Inhibitors in Lymphoma and Drug Therapy

Objective : Lymphoma, impacting individuals across all age groups with a preference for younger males, presents challenges in drug target selectivity. Mucin glycosylation is being investigated as a potential cellular barrier in the treatment of lymphoma. This review explores glycosylation inhibitors as potential enhancers of therapeutic agents for lymphoma treatment.

Methods: A comprehensive literature review identified glycosylation inhibitors and evaluated their efficacy, affordability, and commercial availability in lymphoma therapy. Three PubMed (1946-July 29, 2023) searches were conducted to explore glycosylation inhibition in lymphoma using certain key words and Boolean operators. The first search identified an article investigating global glycosylation inhibition of lymphoma (U937) cells. Another search focused on O-glycosylation inhibitors, resulting in one relevant article. A final search targeted galactosaminyltransferase inhibition, yielding one pertinent article.

Results: The literature review identified five potential compounds and their mechanisms of glycosylation inhibition of lymphoma cell lines: Benzyl-α-GalNAc, tunicamycin, peracetyl N-thioglycolyl-d-galactosamine (Ac5GalNTGc), compounds 1-68A, and 2-68A. Benzyl-α-GalNAc desalylates O-glycans, enhancing cell adhesion to fibronectin. Tunicamycin decreases N-type glycosylation by reducing lectin-reactive oligosaccharide expression and enhances cell adhesion to fibronectin. Ac5GalNTGc inhibits global glycosylation, inducing homotypic clumping. Synthetic uridine-based inhibitors, 1-68A and 2-68A, prevents glycosylation through competitive inhibition of N-acetyl-α-galactosaminyltransferase, and induced apoptosis of T-lymphocyte (Jurkat) cells.

Conclusions: Benzyl-α-GalNAc emerged as a promising and cost-effective glycosylation inhibitor in lymphoma. Ac5GalNTGc demonstrated superior efficacy but lacked commercial availability. Synthetic transferase inhibitors lacked commercial availability despite efficacy. Tunicamycin's toxicity limits its application. Despite Benzyl-α-GalNAc's pragmatic use, further research is needed to elucidate the potential role of glycosylation in drug therapy and targeted drug delivery.