Shedding light on imaging cancer research: Design and synthesis of 1, 8-naphthalimide-based PRMT5-targeted fluorescent ligands

Abstract

Protein Arginine Methyltransferase 5 (PRMT5) is an important player in breast cancer cell activity, and innovative fluorescent ligands targeting this enzyme offer revolutionary, real-time insights into its role in cancer progression, unlocking new avenues for diagnosis and treatment. This study introduces fluorescence-labeled PRMT5 ligands, highlighting their applications in visualizing PRMT5, monitoring enzymatic activity as well as studying toxicity. Herein, we describe the design, synthesis, and cellular imaging of a series of fluorescent ligands that target PRMT5. These ligands are based on the introduction of strong and selective PRMT5 inhibitors into various fluorophores using varied linkers. Among them, compound 7 at 10 μM was shown to exhibit strong fluorescence signals against MCF-7 cells with IC₅₀ values of 29 nM. These advancements could significantly impact tumor treatment due to their ability to specify the target and visualize PRMT5 activity in real time, particularly in breast cancer research.

Keywords: Breast cancer; Cell imaging; Fluorescent ligand; PRMT5.